CLINICAL CHEMISTRY 1

[LEC] UNIT 10: PROTEINS

BASIC STRUCTURE
OUTLINE  Elements:
PROTEINS o Carbon
I. OVERVIEW o Oxygen
1. Basic Structure o Hydrogen
2. General Chemical Properties o Nitrogen
3. Synthesis o Sulfur
4. Catabolism and Nitrogen Balance  Proteins are polymers built from one or more unbranched
5. Classification chains of amino acids
6. Enzymes
o Typical: 200-300 amino acids
7. Hormones
8. Transport Proteins o Smaller: peptides
9. Immunoglobulins o Larger: titin
10. Structural Proteins  Macromolecules
11. Storage Proteins o 6000 Daltons in mass (insulin)
12. Energy Source  Primary structure
13. Osmotic Force o Represents the number and types of amino acids
in the specific amino acid sequence.
II. PLASMA PROTEINS
1. Prealbumin  Secondary structure
2. Albumin o Commonly formed structures stabilized by
3. Globulins hydrogen bonds between the amino acids within
4. a1-Antirypsin the protein
5. a1-Fetoprotein  a-helix
6. a1-Acid Glycoprotein  b-pleated sheet
7. a1-Atichymotrypsin  turns
8. Inter-a-Trypsin Inhibitor
9. Gc-Globulin
o Add strength and flexibility to proteins
10. Haptoglobin
11. Ceruloplasmin Figure No. 1 Secondary structure of protein
12. a2-Macroglobulin
13. Transferrin
14. Hemopexin
15. Lipoproteins
16. β2-Microglobulin
17. Fibrinogen
18. C-Reactive Protein
19. High-Sensitivity CRP
20. Immunoglobulins

III. OTHER PROTEINS OF CLINICAL

SIGNIFICANCE
1. Myoglobin  Tertiary structure
2. Cardiac Troponin o Overall shape, or conformation, of the protein
3. Brain Natriuretic Peptide and N-Terminal- molecule
Brain Natriuretic Peptide o Conformation (fold)
4. Fibronectin
 Spatial relationship of the secondary
5. Adiponectin
6. β-Trace Protein structures to one another
7. Cross-Linked C-Telopeptides o 3-dimesional
8. Cystatin C o Result from the interaction of side chains
9. Amyloid  Stabilized through:
 Hydrophobic effect
 Ionic attraction
OVERVIEW  Hydrogen bonds
 Major functions of proteins:  Disulfide bonds
o Catalyzing biochemical reactions o Affects function and chemical properties of
 Enzymes proteins
o Transporting metals  Quaternary structure
 Iron o Shape of structure that results from the interaction
 Copper of more than one protein molecule or subunits
o Receptor for hormones held together by noncovalent forces
o Providing cellular structure and support  Hydrogen bonds
o Participating in immune response  Electrostatic interactions
 Antibodies
GENERAL CHEMICAL PROPERTIES
 The structure of a protein directly affects its chemical

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA | FEU MT 2023 1
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM

properties SYNTHESIS
 Proteins can be positively or negatively charged  Most plasma proteins are synthesized in the liver and
o Contain many ionizable groups on the side chains secreted by the hepatocyte into circulation
of their amino acids as well as on their N- and C-  Immunoglobulins are an exception
terminal ends o Synthesized in plasma cells
 Basic groups:  The amino acid sequence of a polypeptide chain is
o Lysine determined by a corresponding sequence of bases
o Arginine (guanine, cytosine, adenine, and thymine) in the DNA
o Histidine contained in the specific gene
 Acidic groups:  Codons
o Glutamate o Set of 3 nucleotides (each standing for a specific
o Aspartic acid amino acid)
o Cysteine o Total number of possible codons: 64
o Tyrosine  Transcription
 The pH of the solution, the pKa of the side chain, and the o Formation of complementary strand of mRNA
side chain's environment influence the charge on each side o The mRNA is manufactured in the cell nucleus
chain and then translocated across the nuclear
 Henderson-Hasselbalch equation: membrane into the cytoplasm for translation
o Describes the relationship between pH, pKa, and  Translation
charge for amino acids o mRNA strand is used as a template for protein
synthesis by the ribosome
Figure No. 2 Henderson-Hasselbalch equation  loaded onto ribosome
 read 3 nucleotides at a time by matching
each codon to its base pairing anticodon
 located on tRNA
o short-chain RNA that
 As the pH of a solution increases, becoming more occurs freely in the
alkaline, deprotonation of the acidic and basic groups cytoplasm
occurs o Each amino acid has a specific tRNA that
o Carboxyl groups are converted to carboxylate contains three bases corresponding to the three
anions (R-COOH  R-COO-) bases in the mRNA
o Ammonium groups are converted to amino o The tRNA carries its particular amino acid to the
groups (R-NH3+  R-NH2) ribosome and attaches to the mRNA in
 Isoelectric point (pI) accordance with the matching codon
o pH at which amino acids have no net charge o Amino acids are aligned in sequence and joined
 number of positively charged groups together
equals the number of negatively  Protein synthesis occurs at a rate of approximately two to
charged groups six peptide bonds per second
o pH > pI = net negative charge  Intracellular proteins
o pH < pI = net positive charge o Synthesized on free ribosomes
 The net charge on the surface of a protein depends on the  Proteins made by the liver for secretion
number and type of amino acids it contains as well as the o Synthesized on ribosomes attached on RER
pH of its environment  Hormones (thyroxine, GH, insulin, and testosterone) may
 Protein’s solubility assist in controlling protein synthesis
o Dependent on the charge on its surface
 Hydrophilic Figure No. 3 Protein synthesis
 There is a charge at the protein
surface
o Lowest solubility = pI
o Solubility of proteins in blood requires a pH of
7.35-7.45
 Denaturation
o Loss of native/naturally occurring folded
structures in proteins
o Structure of proteins is disturbed
 Loses its functional and chemical
characteristics
o Causes:
 Heat
 Hydrolysis (by strong acid/base)
 Enzymatic action
 Exposure to urea or other substances
 Exposure to UV light

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023 2
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM

 Ketoacids
o Oxidized by means of
the citric acid cycle
o Converted into
glucose/fat

CLASSIFICATION
 Proteins are commonly classified by the functions they
perform

ENZYMES
 Proteins that catalyze biochemical reactions
 Normally found intracellularly, but are release into the
bloodstream as a result of tissue damage
 Examples commonly used in clinical laboratories to
evaluate tissue damage:
o Transaminases
o Dehydrogenases
o Phosphates

CATABOLISM AND NITROGEN BALANCE HORMONES

 Unlike fats and carbohydrates, nitrogen has no designated  Chemical messenger proteins that control the actions of
storage specific cells or organs
 Most proteins in the body are repetitively synthesized and  Directly affect the ff:
then degraded allowing for efficient recycling of amino o Growth and development
acids o Metabolism
o A balance exists between protein synthesis o Sexual function
(anabolism) and protein breakdown (catabolism) o Reproduction
o Turnover of proteins: o Behavior
 125-220g of protein/day  Examples commonly tested in clinical laboratories (blood,
 Nitrogen balance urine, saliva):
o Maintained by equal intake and excretion of o Insulin
amino acids o Testosterone
o Positive nitrogen balance o GH
 Their nitrogen intake exceeds their loss o FSH
 Pregnant women, growing children, and o Cortisol
adults recovering from major illness
o Negative nitrogen balance TRANSPORT PROTEINS
 More nitrogen is excreted than is  Involved in the transport of ions, small molecules, or
incorporated into the body macromolecules, such as hormones, vitamins, minerals,
 Excessive tissue destruction, such as and lipids, across a biologic membrane
burns, wasting diseases, continual high  Examples:
fevers, or starvation o Hemoglobin
 Breakdown of protein occurs in the GIT and kidneys, but o Albumin
primarily in the liver o Ceruloplasmin
 2 routes for converting intracellular proteins to free amino o Haptoglobin
acids o Transferrin
o Lysosomal pathway IMMUNOGLOBULINS (ANTIBODIES)
o Cytosolic pathway  Proteins produced by B cells in the BM
 Transamination  Mediate humoral immune response to identify and
o Central reaction that removes amino acid nitrogen neutralize foreign antigens
from the body  Examples that are of clinical importance:
o Involves moving an a-amino group from a donor o IgG
a-amino acid to the keto carbon of an acceptor a- o IgM
ketoacid o IgE
o Transaminases o IgA
 Enzymes that catalyze these reversible
Structural Proteins
reactions
 Produces:  Fibrous proteins provide structure to many cells and
 Ammonia tissues throughout the body, such as muscle, tendons, and
o Converted into urea bone matrix.
by the urea cycle  Collagen, elastin, and keratin are examples of structural
o Excreted in urine proteins.

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023 3
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM

Storage Proteins filaments or subunits, are asymmetrical

 Storage proteins serve as reservoirs for metal ions and and usually inert, and are generally
amino acids so they can be stored without causing harm water insoluble due to their hydrophobic
and released later. R groups.
 Ferritin is a commonly measured protein that stores iron  provide structure to cells, such
for later use in the manufacture of hemoglobin. as connective tissues, tendons,
bone, and muscle.
Energy Source  Examples of fibrous proteins
include troponin and collagen.
 Some proteins serve as an energy source for tissues and
 Conjugated proteins – consist of a protein and a non-
muscle.
protein.
 Creatine is one example of an energy source protein as it
o The nonamino part of a conjugated protein is
helps to supply energy to cells throughout the body, but is
generally referred to as the prosthetic group.
primarily found in muscle tissue.
o The prosthetic group may be a lipid,
carbohydrate, porphyrin, metal, etc. It is the
Osmotic Force prosthetic group that defines the characteristics of
 Some proteins function in the distribution of water a conjugated protein.
throughout the compartments of the body. o Examples of conjugated proteins are
 Their colloid osmotic force, due to their size, does not metalloproteins, glycoproteins, lipoproteins, and
allow proteins to cross the capillary membranes. nucleoproteins.
 As a result, water is absorbed from the tissue into the  Metalloproteins - have a metal ion
venous portion of the capillary. attached to the protein, either directly, as
 When the concentration of plasma proteins is significantly in ferritin, which contains iron, and
decreased, the concomitant decrease in the plasma ceruloplasmin, which contains copper,
colloidal osmotic (oncotic) pressure results in increased or as a complex metal such as
levels of interstitial fluid and edema. hemoglobin and flavoproteins.
 This often occurs in renal disease when proteins are  Glycoproteins - molecules with a
inappropriately excreted in urine and plasma protein composition of 10% to 40%
concentrations are decreased. carbohydrate
 Examples of glycoproteins are
Function of Proteins haptoglobin and α1-
antitrypsin.
 Simple Proteins  Mucoprotein / Proteoglycan –
o Contain peptide chains composed of only amino carbohydrate percentage is greater than
acids. 40%.
o May be globular or fibrous in shape.  An example of a mucoprotein is
 Globular Proteins – are globe-like and mucin, which is a lubricant that
have symmetrical proteins that are protects body surfaces from
soluble in water. friction or erosion
 Function as transporters,  Increased mucin production
enzymes, and messengers. occurs in many
 Examples of globular proteins adenocarcinomas, including
are albumin, hemoglobin, and cancer of the pancreas, lung,
the immunoglobulins, IgG, IgA, breast, ovary, and colon.
and IgM.  Moreover, mucins are also
 Fibrous Proteins – form long protein being investigated for their
potential as diagnostic
Energy Tissue nutrition markers.
Osmotic force Maintenance of water
distribution between cells
 Nucleoproteins – are those proteins
and tissue, interstitial
that are combined with nucleic acids.
compartments, and the
vascular system of the body.  Chromatin is an example of a
nucleoprotein as it is a complex
Acid-base balance Participation as buffers to
of DNA and protein that makes
maintain pH
up chromosomes.
Transport Metabolic substances
Antibodies Part of immune defense
Plasma Proteins
system
 Are the most commonly analyzed proteins in the clinical
Hormones Hormones and receptors
laboratory and can be divided into two major groups: albumin
Structure Connective tissue and globulins.
Enzymes Catalysts  Analysis of blood specimens will typically include four protein
Hemostasis Participation in coagulation measurements:
of blood o Total protein

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023 4
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
o Albumin
o Globulin
o Albumin-to-globulin (A/G) ratio
Prealbumin / Transthyretin
 It migrates before albumin in classic serum protein
electrophoresis (SPE).
 Can also be separated using high resolution
electrophoresis (HRE) or immunoelectrophoresis
techniques.
 It is a transport protein for the thyroid hormones, thyroxine
(T4), and triiodothyronine (T3).
 Forms a complex with retinol-binding protein to transport
retinol (vitamin A) and is rich in the amino acid tryptophan.
 A low prealbumin may also indicate poor nutritional status.
 Diets deficient in protein may not provide sufficient amino
acids for adequate protein synthesis by the liver resulting
in decreased plasma concentrations of prealbumin,
albumin, and β-globulins.
 Has a half-life of approximately 2 days, so blood
concentrations of prealbumin decrease faster than do
those of other proteins with a longer half-life when protein
synthesis is inhibited.
 Blood concentrations of prealbumin may be increased in
patients receiving steroid therapy, who have issues with
alcohol abuse, or who are in chronic renal failure.
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
Albumin
 Is synthesized in the liver at a rate of 9 to 12 g/day and is
the most abundant protein in the plasma.
 Also exists in the extravascular (interstitial) space.
 The total amount of extravascular albumin exceeds the
total intravascular amount by about 30%; however, the
concentration of albumin in plasma (albumin mass/plasma
volume) is much greater than its concentration in the
interstitial space.
 Leaves the bloodstream at a rate of 4% to 5% of the total
intravascular albumin concentration per hour. This rate of
movement is known as the transcapillary escape rate,
which measures systemic capillary efflux of albumin.
 Is responsible for nearly 80% of the colloid osmotic
pressure (COP) of the intravascular fluid, which maintains
the appropriate fluid balance in the tissue.
 Albumin also buffers pH and is a negative acute-phase
reactant protein.
 A primary function of albumin is its capacity to bind and
transport various substances in the blood.
 Albumin is involved in the transport of thyroid hormones,
unconjugated bilirubin, fat-soluble hormones, iron, fatty
acids, calcium (Ca 2+), magnesium (Mg 2+, and many
drugs such as salicylic acid (aspirin).
 Also binds certain dyes, which is the basis for many of the
methods used for quantitation of albumin.
 Several recent studies have focused on the clinical
applications of glycated (or glycosylated) albumin as a
more sensitive indicator of short-term hyperglycemic
control than glycated hemoglobin.
 Glycated hemoglobin represents trends in blood glucose
over a period of 3 months or approximately 120 days,
which is the life span of red blood cells.
 As the half-life of serum albumin is 20 days, glycated
albumin represents serum glucose patterns approximating
1 month.
 Decreased blood concentrations of albumin are most
commonly associated with an acute inflammatory
response as albumin is a negative acute-phase reactant.
 Liver and kidney disease may also result in low blood
albumin concentrations.
 Albumin is normally excreted in very small amounts by the
kidneys; however, increased renal loss of albumin
commonly occurs in renal disease.
o This increased excretion occurs when the
glomerulus no longer restricts the passage of
proteins from the blood into the ultrafiltrate as
occurs in nephrotic syndrome.
 Low albumin concentrations may also be the result of
malnutrition and malabsorption in which an inadequate
ingestion of proteins or amino acid-rich foods results in
decreased protein synthesis by the liver.
 Less commonly, low blood albumin concentrations occur
as a result of hypothyroidism, burns or exfoliative
dermatitis, dilution by excessive intake (polydipsia),
orinfusion of liquids (intravenously).
 Albumin may be redistributed by hemodilution, increased
capillary permeability, or decreased lymph clearance
 Mutations resulting from an autosomal recessive trait can
cause an absence of albumin, known as analbuminemia,
or presence of albumin that has unusual molecular
characteristics, which is referred to as bisalbuminemia.
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
o Bisalbuminemia is demonstrated by the
presence of two albumin bands during
electrophoresis instead of the single band usually
observed.
o Both analbuminemia and bisalbuminemia are
rare.
 Abnormally high albumin concentrations are seldom
clinically important and are generally associated with
dehydration or excessive albumin infusion.
Globulins
 The globulin group of proteins consists of α1, α2 , β, and γ
fractions.
 Each fraction consists of a number of different proteins with
individual functions.
o α1-Antitrypsin
 Is a glycoprotein synthesized mainly in
the liver.
 Its main function is in the inhibition of the
protease, neutrophil elastase.
 Neutrophil elastase is released from
leukocytes during an infection, but can
also destroy alveoli leading to
emphysema if not inhibited by α1 -
antitrypsin.
 Mutations in the SERPINA1 gene can
lead to a deficiency of α1 -antitrypsin
protein or an abnormal form of the
protein that does not properly control
neutrophil elastase.
 The abnormal form of α1 -antitrypsin can
also accumulate in the liver causing
cirrhosis.
 α1 - Antitrypsin is a positive acute-phase
reactant; therefore, increased levels of
α1 - antitrypsin are seen in inflammatory
reactions as well as in pregnancy and
contraceptive use.
 Several phenotypes of α1 -antitrypsin
deficiency have been identified.
 The most common phenotype
is MM (allele PiM) and is
associated with normal α1 -
antitrypsin activity
 Other alleles are Pi S , Pi Z , Pi
F , and Pi (null).
 The homozygous phenotype
ZZ individual is at greatest risk
for developing hepatic and
pulmonary disease from α1 -
antitrypsin deficiency.
 Replacement therapy using purified α1
-antitrypsin protein from pooled
plasma can dramatically slow disease
progression.
 It is also recommended that individuals
with α1 -antitrypsin deficiency do not
smoke.
 Decreased α1 -antitrypsin levels are
most often identified in the clinical
laboratory by the lack of an α1 –globulin
band on serum protein electrophoresis
because α1 -antitrypsin accounts for
approximately 90% of the α1 -globulin
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
fraction, which migrates immediately
following albumin.
 Quantitative methods used to confirm α1
-antitrypsin deficiency are radial
immunodiffusion and automated
immunonephelometric assays.
 Phenotyping may also be performed
using immunofixation techniques.
o α1-Fetoprotein
 Is synthesized in utero by the developing
embryo and fetus and then by the
parenchymal cells of the liver.
 AFP concentrations decrease gradually
after birth, reaching adult concentrations
by 8 to 12 months of age
 Conditions associated with an elevated
AFP concentration include spina bifida,
neural tube defects, abdominal wall
defects, anencephaly, general fetal
distress, and the presence of twins.
 Low levels of maternal AFP indicate an
increased risk for trisomy 21 (Down
syndrome) and trisomy 18 (Edwards
syndrome).
 AFP screening is performed between 15
and 20 weeks gestation when maternal
AFP increases gradually; therefore,
interpretation requires accurate dating of
the pregnancy.
 Measurements of AFP can be affected
by laboratory specific technique, which
can result in difficulty comparing
absolute results between centers.
 AFP levels are also affected by maternal
weight, race, and diabetes; therefore,
test results need to be adjusted for these
variables.
 To account for these maternal variables,
the multiple of the median or MoM is
utilized.
 MoM is a reflection of an
individual patient's value
compared with the median.
 MoM is calculated by dividing
the patient's AFP value by the
median reference value for that
gestational age.
 Most screening laboratories
use 2.0 MoM as the upper limit
and 0.5 MoM as the lower limit
of normal for maternal serum.
 The methods commonly used
for AFP determinations are
radioimmunoassay (RIA) and
enzyme-labeled
immunoassay (EIA).
 Maternal screening tests have been
established as a triple or quadruple test
group using a mathematical calculation
involving the concentrations of AFP,
human chorionic gonadotropin (hCG),
unconjugated estriol, and inhibin A.
 These calculations are used to
determine a numerical risk for
chromosomal abnormalities in
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
the fetus, which can be
compared with an established
cutoff.
 The interpretation of these test
results should be provided by a
genetic counselor or clinician to
aid parents and their
physicians in making decisions
about the management of the
pregnancy.
 AFP may also be used as a tumor
marker and is fractionated by affinity
electrophoresis into three isoforms (L1,
L2, and L3) based on their reactivity with
the lectin Lens culinaris agglutinin
(LCA).
 AFP-L3 is now being considered as a
tumor marker for the North American
population for screening chronic liver
disease patients for hepatocellular
carcinoma (HCC).
 Results for AFP-L3 are reported as a
ratio of LCA-reactive AFP to total AFP
(AFP-L3%).
 Studies have shown that AFP-L3% test
results of greater than 10% are
associated with a sevenfold increase in
the risk of developing HCC within the
next 21 months.
α1- Acid glycoprotein (AAG) or orosomucoid
 α1 -Acid glycoprotein (AAG) or orosomucoid
o A major plasma glycoprotein
o Negatively charged even in acidic solutions.
o Produced by the liver
o Positive acute-phase reactant.
o AAG can also regulate immune responses
according to some studies.
 There is a strong similarity in the amino acid sequences
of AAG and immunoglobulin.
o AAG elevates during:
 stress, inflammation, tissue damage,
acute myocardial infarction, trauma,
pregnancy, cancer, pneumonia,
rheumatoid arthritis, and surgery.
o Serum AAG concentrations can also be used in
the diagnosis and evaluation of neonatal
bacterial infections.
o The binding of drugs to plasma protein has
become increasingly important in the diagnosis
of drug action, distribution, and disposition.
 analytic methods used for the determination of AAG are:
o Radial immunodiffusion
o Immunoturbidity
o Nephelometry
 Immunofixation techniques is also used
to study inherited variants with a
reference interval of 50 to 120 mg/dL
for healthy individuals.
α1- Antichymotripsin
 α1-Antichymotrypsin
o α-globulin glycoprotein and a serine proteinase
inhibitor (serpin) family.
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
o It inhibits the activity of the enzymes:
 cathepsin G, pancreatic elastase, mast
cell chymase, and chymotrypsin
 Through cleaving them into a different
shape (conformation).
o It is produced in the liver
o Positive acute-phase protein that increases
during inflammation.
 Deficiency in α1-Antichymotrypsin is associated with liver
disease due to decreased synthesis.
 Mutations in α1 -antichymotrypsin is linked in patients with
Parkinson's disease and chronic obstructive pulmonary
disease.
 α1 -Antichymotrypsin is also associated with the
pathogenesis of Alzheimer's disease (it is an integral
component of the amyloid deposits in Alzheimer's
disease).
Inter- α-trypsin inhibitors (it is)
 Inter-α-trypsin inhibitors (ITIs)
o A family of serine protease inhibitors
o It is assembled from two precursor proteins:
o Light chain and one or two heavy
chains.
 Only one type of light chain
o ITIH molecules- have been shown to
play a particularly important role in
inflammation and carcinogenesis.
 There are five different homologous
heavy chains (ITIHs).
 Elevations in ITIs are often seen in
inflammatory disorders
Gc-Globulins
 Gc-Globulin (Gc)
o Known as group-specific component or vitamin
D– binding protein.
o Mainly synthesized by hepatocytes
o Major carrier protein for vitamin D and its
metabolites.
o It can transports fatty acids and endotoxins.
o Gc binds actin released from cells upon injury
 Gc–actin complexes are rapidly cleared
from the circulation which can prevent
harmful effects of actin filaments in
blood vessels.
 The decrease in Gc concentration makes it as a
prognostic indicator of survival of patients with significant
tissue injury and patients with hepatic failure.
 Gc plays an important role in bone formation and in the
immune system considering that it can act as a
cochemotactic factor to facilitate chemotaxis of
neutrophils and monocytes.
 Due to genetic polymorphism in the Gc gene (codominant
alleles) three major electrophoretic variants of Gc exist:
o Gc2, Gc1s, and Gc1f.
 Elevations of Gc-globulin are seen in the third trimester
of pregnancy and in patients taking estrogen oral
contraceptives.
 Severe liver disease and proteinlosing syndromes are
associated with low Gc-Globulin.
 Immunonephelometry- method of choice for Gc
measurements.
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
Haptoglobin
 Haptoglobin (Hp)
o α2 -glycoprotein synthesized in the liver
o a tetramer consisting of two α and two β chains.
o a positive acute-phase protein that increases in
many inflammatory diseases:
 Such as: ulcerative colitis, acute
rheumatic disease, acute myocardial
infarction, and severe infection.
 Or in conditions such as burns and
nephrotic syndrome when large
amounts of fluid and lower-molecular-
weight proteins are lost
o haptoglobin are not generally used to diagnose
or monitor either of these conditions.
 Its main function is to bind free
hemoglobin to prevent the loss of its
constituent, iron, into the urine.
 “When haptoglobin and hemoglobin
attach, the reticuloendothelial cells,
predominantly in the spleen, remove
the haptoglobin–hemoglobin complex
from circulation so the hemoglobin
constituents, iron and amino acids, can
be recycled and haptoglobin is
destroyed”.
 It is primarily used to evaluate possible hemolytic anemia
and to distinguish it from anemias due to other causes.
o Patients usually have an increased reticulocyte
count, decreased red blood cell count,
decreased hemoglobin, and decreased
hematocrit.
o Patients with a hemolytic anemia
 Also have a decreased haptoglobin
(due to its destruction by the
reticuloendothelial system)
 If the haptoglobin is normal and the
reticulocyte count is ↑, it is likely the
anemia is due to destruction of red
bloods in organs such as the spleen
and liver.
o If the haptoglobin concentration and the
reticulocyte count are within the normal, it is
likely the anemia is not due to red blood cell
breakdown.
o If haptoglobin concentrations are decreased
without any sign of hemolytic anemia, it is
possible the liver is not producing adequate
amounts of haptoglobin.
 An individual's haptoglobin phenotype has been reported
as an independent risk factor for cardiovascular disease
(CVD) in patients with type 2 diabetes mellitus.
 Three phenotypes of haptoglobin are found in humans:
o Hp1-1, Hp2- 1, and Hp2-2.
 Homozygous Hp1-1 yields one band
during electrophoresis. Peptide chains
form polymers with each other and with
haptoglobin 1 chains to provide the
other two electrophoretic patterns,
which have been designated as Hp2-1
and Hp2-2 phenotypes.
Radial immunodiffusion and immunonephelometric
methods have been used for the quantitative
determination of haptoglobin.
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
Ceruloplasmin
 Ceruloplasmin
o Copper-containing, α2 -glycoprotein enzyme
o synthesized in the liver
o A positive acute-phase reactant and ↑ during
inflammation, severe infection, and tissue
damage and cancers.
o May also be ↑ during pregnancy and those who
takes estrogen, oral contraceptives, and
carbamazepine, phenobarbital, and valproic
acid.
o 90% or more of total serum copper is bound to
ceruloplasmin – 10% bound to albumin.
 Ceruloplasmin, blood and urine copper tests is used to
aid in the diagnosis of Wilson's disease.
o Wilson's is an autosomal recessive inherited
disorder associated with decreased
concentrations of ceruloplasmin,
 Typically 0.1 g/L, and excess storage of
copper in the liver, brain, and other
organs, which results in hepatic
cirrhosis and neurologic damage.
o In Wilson's disease, the total serum copper
concentration is decreased, but the urinary
excretion of copper is increased.
o Copper is also deposited in the cornea,
producing the characteristic Kayser-Fleischer
rings.
o Low ceruloplasmin is also seen in malnutrition,
malabsorption, severe liver disease, nephrotic
syndrome, and Menkes' syndrome, in which a
decreased absorption of copper results in a
decrease in ceruloplasmin and distinctive “kinky
hair.”
Early analytic method of ceruloplasmin is based
on its copper oxidase activity, can be detected
through immunochemical methods, radial
immunodiffusion and nephelometry.
a2-Macroglobulin
 α2-Macroglobulin
o A tetramer of four identical subunits
o Synthesized by the liver
o A major component of the α2 band in protein
electrophoresis.
o It inhibits proteases such as trypsin, thrombin,
kallikrein, and plasmin by means of a bait region
that entraps proteinases.
 Entrapment reduces the accessibility of
the proteinase functional sites (mostly
seen in large molecules, but it does not
completely inactivate them).
 After binding with and inhibiting
proteases, α2 -macroglobulin is
removed by the reticuloendothelial
system.
 In nephrosis
o Concentrations of serum α2 -macroglobulin may
due to its large size that inhibits filtration at the
renal glomeruli, making α2 -macroglobulin useful
in evaluation of renal disease.
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
o ↑ Concentrations may also be seen in patients
with diabetes or liver disease and patients using
contraceptive.
o During pregnancy, serum α2 -macroglobulin
concentrations may ↑ by 20%.
Analytic methods- radial immunodiffusion,
immunonephelometry, enzyme-linked
immunosorbent assay (ELISA), and latex
agglutination immunoassay.
Transferrin
 Transferrin siderophilin
o A negative acute-phase glycoprotein
o Synthesized by the liver.
o A major component of the β-globulin fraction on
protein electrophoresis
o Also plays an important role in the transport of
iron.
o Transferrin binds and transports iron to its
storage sites
 Liver, where it is incorporated into
apoferritin, another protein, to form
ferritin.
o Transferrin also carries iron to the bone marrow
 And synthesizes hemoglobin and other
iron-containing compounds.
 Iron bound to transferrin= less than
0.1% (4 mg) of the total body iron,
most important iron pool.
 Transferrin also prevents iron from
being inappropriately deposited in
tissues during temporary increases in
absorbed iron or free iron.
o Transferrin are routinely measured to determine the
cause of anemia
o To gauge iron metabolism, and to determine the
iron-carrying capacity of the blood.
o In iron deficiency anemia, transferrin
concentrations are abnormally ↑ works as a
compensation mechanism.
o While low transferrin can impair hemoglobin production
and lead to anemia.
o A deficiency of plasma transferrin may also
result in the inappropriate accumulation and
precipitation of iron in tissues as hemosiderin.
o A ↑ of iron bound to transferrin is found on
hemochromatosis
 Excess iron is deposited in the tissue,
especially the liver and the pancreas.
Characterized by having bronze skin,
cirrhosis, diabetes mellitus, and low
plasma transferrin levels.
o Transferrin is low in liver disease or when there is not
enough protein in the diet.
o A decreased transferrin concentration can also be due to
excessive loss through the kidneys in protein losing
disorders such as nephrotic syndrome. Can also be seen
during infection, inflammation, and malignancy.
o Atransferrinemia- Inherited autosomal recessive trait due
to mutation of both transferrin genes. Characterized by
anemia and iron deposition (hemosiderosis) in the liver
and heart and damage to the heart can lead to heart
failure.
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
 This disease can be effectively treated
by plasma infusions of transferrin
 Analytic methods used for the quantitation-
immunodiffusion and immunonephelometry.
 Total iron-binding capacity (TIBC) is typically measured
along with serum iron to evaluate either iron deficiency or
iron overload.
 The iron concentration divided by TIBC gives the
transferrin saturation, which is a more useful indicator of
iron status than iron or TIBC alone.
 In iron deficiency, total serum iron is low, but TIBC is
increased, and transferrin saturation becomes very low.
 In iron overload, total serum iron is high and TIBC is low
or normal, causing transferrin saturation to increase. It is
customary to test for transferrin, rather than TIBC, when
evaluating nutritional status or liver function.
LIPOPROTEINS
 complexes of proteins and lipids. Function is to transport
cholesterol, triglycerides, and phospholipids in the
bloodstream.
 subclassified according to their apolipoprotein and lipid
content.
o chylomicrons, very-low-density lipoproteins
(VLDL)
o intermediate-density lipoproteins (IDL)
o low-density lipoproteins (LDL)
o high-density lipoproteins (HDL).
β2-MICROGLOBULIN
 light chain component of the major histocompatibility
complex or human leukocyte antigen (HLA).
 found on the surface of most nucleated cells and is present
in high concentrations on lymphocytes.
 filtered by the renal glomerulus, but is almost completely
reabsorbed and catabolized in the proximal tubules.
 seen on high-resolution electrophoresis, but because of its
low concentration, it is usually measured by immunoassay
 Elevated serum levels:
o result of impaired clearance by the kidney or
overproduction of the protein that occurs in a
number of inflammatory diseases: rheumatoid
arthritis and systemic lupus erythematosus
(SLE)
o In patients with HIV, a high B2M level in the
absence of renal failure indicates a large
lymphocyte turnover rate, suggesting the virus is
killing lymphocytes.
COMPLEMENT
 synthesized in the liver as single polypeptide chains and
circulate in the blood as nonfunctional precursors.
 COMPLEMEN C3
o most abundant complement protein in the human
serum.
o important in the pathogenesis of age-related
macular degeneration, and this finding further
underscores the influence of the complement
pathway in the pathogenesis of this disease.
o used as a screening test because of its pivotal
position in both the classic and alternative
pathway.
 COMPLEMEN C4
o second most abundant.
 CLASSIC PATHWAY
o activation of these proteins begins when the first
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
complement factor, C1q, binds to an antigen–
antibody complex.
o each complement protein (C2–C9) is then
activated sequentially and can bind to the
membrane of the cell to which the antigen–
antibody complex is bound, leading to lysis of the
cell.
 PROPERDIN PATHWAY
o alternate pathway for complement activation.
o early components are bypassed and the process
begins with C3.
o triggered by different substances and does not
require the presence of an antibody;
 Increased levels of both C3 and C4
o linked to acute inflammatory disease and tissue
inflammation.
 Decreased levels of C3
o associated with autoimmune disease, neonatal
respiratory distress syndrome, bacteremia, tissue
injury, and chronic hepatitis.
 Decreased levels of C4
o seen in disseminated intravascular coagulation
(DIC), acute glomerulonephritis, chronic hepatitis,
and SLE.
 C3 and C4 are the most commonly measured in the
clinical laboratory. C3 concentrations, however, are not
the most sensitive indicator of classic pathway activation
and a decreased complement C4 concentration is
frequently found to be a more sensitive measure of
mild classic pathway activation.
 Methods for measuring complement include nephelometric
immunoassay and turbidimetry.
FIBRINOGEN
 one of the largest proteins in blood plasma.
 synthesized in the liver and is classified as a glycoprotein
because it has considerable carbohydrate content.
 function is to form a fibrin clot when activated by thrombin
 all fibrinogen is virtually removed in the clotting process
and should not be present in serum specimens.
 a positive acute-phase reactant and increases significantly
during an inflammatory process.
 also rise with pregnancy and the use of oral contraceptives.
 decreased values generally reflect extensive
coagulation, during which fibrinogen is consumed.
 clottable protein and its measurement in the laboratory is
determined by analyzing clot formation.
 it is a clottable protein and its measurement in the
laboratory is determined by analyzing clot formation.
 concentration of fibrinogen is proportional to the time
required to form a clot after the addition of thrombin to
citrated plasma.
 FIBRIN SPLIT PRODUCTS
o degradation products of fibrinogen and fibrin
o determined by immunoassay methods such as
radial immunodiffusion, nephelometry, and RIA.
 PLASMA ELECTROPHORESIS
o fibrinogen can be seen as a small, distinct band
between the β- and γ-globulin regions and
indicates use of plasma instead of serum.
C-REACTIVE PROTEIN
 synthesized in the liver
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
 one of the first acute-phase proteins to rise in response to
inflammatory disease.
 rises sharply whenever there is tissue inflammation.
 INFLAMMATION
o has been demonstrated through many studies to
be important in the development of
atherosclerosis, which is the fatty deposit that
accumulates in the inner lining of arteries
 ATHEROSCLEROSIS
o disease of lipid accumulation
o represents a chronic inflammatory process
causing an elevated CRP
 Major factors that promote atherosclerosis: cigarette
smoking, hypertension, plaque causing lipoproteins, and
hyperglycemia.
 Elevated levels of CRP
o stimulate the production of tissue factor, which
initiates coagulation, activates complement, and
binds to LDL in the atherosclerotic plaque.
o CRP concentrations are measured during the
evaluation of arteriosclerosis and risk for
cardiovascular disease.
 Reduced CRP levels
o weight loss, diet, exercise, and smoking cessation
and administration of pharmacologic agents such
as statins.
 individuals with CRP levels greater than 3 mg/L have four
to six times greater risk for development of diabetes than
individuals with lower levels of CRP.
 result above 1 mg/dL is usually considered high for CRP,
and most infections and inflammations result in CRP levels
above 10 mg/dL.
HIGH-SENSITIVITY CRP
 named for a monoclonal antibody–based test methodology
that can detect CRP at levels below 1 mg/L.
 most commonly used to determine risk of CVD.
 CONCENTRATIONS:
o Less than 1mg/L-low risk
o 1-3 mg/L-moderate
o Greater than 3mg/L-high risk
 high levels of hsCRP consistently predict recurrent
coronary events in patients with unstable angina and AMI.
 elevated hsCRP concentrations are also associated with
lower survival rates in these patients.
IMMUNOGLOBULINS
 glycoproteins composed of 82% to 96% protein and 4% to
18% carbohydrate.
 they are produced by white blood cells, known as B cells,
that confer humoral immunity.
 these proteins consist of:
o 2 identical heavy (H) chains
o 2 identical light (L) chains linked by 2 disulfide bonds.
 five classes (isotopes) of immunoglobulins, IgG, IgA, IgM,
IgD, and IgE, based on the type of heavy chain they
possess; their heavy chains are γ, α, μ, δ, and ε,
respectively.
 N-terminal region (heavy and light chains)
o exhibit highly variable amino acid composition
referred to as VH and VL, which is involved in
antigen binding.
o constant domains of light and heavy chains are
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
referred to as CL and CH, respectively, which is
involved in complement binding, placental
passage and binding to cell membranes.
 IMMUNOGLOBULIN CLASS SWITCHING/ ISOTYPE
SWITCHING
o biologic mechanism that changes an antibody
from one class to another.
o occurs after activation of the B cell, which allows
the cell to produce different classes of antibody.
o only the constant region of the antibody heavy
chain changes during class switching
 “Y” shape (antibody molecule)
o recognizes specific foreign objects.
o region of the antibody is called the Fab
(fragment, antigen binding) region.
o composed of one constant and one variable
domain from each heavy and light chain of the
antibody.
o base of the Y is called the Fc, or fragment,
crystallisable, region and is composed of two
heavy chains that contribute two or three constant
domains depending on the class of the antibody.
 IgG
o most abundant class of antibodies found in
blood plasma and lymph
o act on bacteria, fungi, viruses, and foreign
particles by agglutination, opsonization, and
complement activation and by neutralizing toxins.
o increased IgG levels
 liver diseas
 infections
 IgG myeloma
 parasitic disease
 rheumatic diseases.
o decreased IgG levels
 acquired immunodeficiency
 increased susceptibility to infections
 hereditary deficiency
 protein-losing states
 non-IgG myeloma.
o can cross the placenta so any IgG present in a
newborn's serum was synthesized by the mother
 IgA
o main immunoglobulin found in mucous
secretions, including tears, saliva, colostrum,
vaginal fluid
o secretions from the respiratory and
gastrointestinal mucosa, and is also found in
small amounts in blood.
o Two isotypes: IgA1 (90%) and IgA2 (10%)
 IgA1
found in serum and is made by bone
marrow B cells
 IgA2
made by B cells located in the mucosa.
o Classified based on location: serum IgA and
secretory IgA
 Secretory IgAs
polymers of two to four IgA monomers
linked by two additional chains, one
being the J chain (Joining chain), which
is a polypeptidecontaining cysteine and
completely different structurally from
other immunoglobulin chains.
o Increases in serum IgA
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
 found in liver disease
 infections
 autoimmune diseases
o decreased IgA
 found in depressed protein synthesis
 immunodeficiency.
 IgM
o first antibody to appear in response to antigenic
stimulation and is present in B cells.
o pentamer and contains a J chain, which also
makes it an important secretory immunoglobulin.
o Increased IgM concentration
 found in toxoplasmosis
 primary biliary cirrhosis
 cytomegalovirus
 rubella
 herpes
 syphilis
 bacterial and fungal diseases.
o Decreased IgM concentration
 seen in protein-losing conditions
 hereditary immunodeficiency.
o IgM cannot cross the placenta, but it is the only
immunoglobulin synthesized by the neonate.
 IgD
o present on the surface of most, but not all, B cells
early in their development though little IgD is ever
released into the circulation
o help regulate B-cell function; however, the
specific function of circulating IgD is largely
unknown
o its concentration is typically increased in
infections, liver disease, and connective tissue
disorders.
 IgE
o produced by B cells and plasma cells and is
associated with allergic and anaphylactic
reactions
o concentration of IgE in the circulation is very low
o an elevated IgE concentration is not diagnostic of
any single condition, but elevated IgE levels are
observed in many inflammatory and infectious
diseases, including asthma and hay fever.
o monoclonal increases are seen in IgE myeloma,
but are rare.
 Determination of immunoglobulins:
o radial immunodiffusion
o nephelometry
o turbidimetry
o electrochemiluminescent immunoassay (ECLIA)
o RIA
 Fluorescent immunoassay techniques and
immunonephelometric assays have also been used, and
solid-phase displacement RIAs, double-antibody RIAs,
solid-phase sandwich RIAs, and nephelometry are all used
to measure IgE.
 Monoclonal increases are seen on serum protein
electrophoresis (SPE) patterns as spikes.
OTHER PROTEINS OF CLINICAL SIGNIFICANCE
MYOGLOBIN
 single-chain globular protein of 153 amino acids,
containing a heme prosthetic group.
 primary oxygen-carrying protein found in striated skeletal
11
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM

and cardiac muscle, accounting for approximately 2% of  represents a complex of regulatory proteins:
total muscle protein. o troponin C (TnC)
 most myoglobin found in cells is dissolved in the o troponin I (cTnI)
cytoplasm. o troponin T (cTnT)
 can reversibly bind oxygen similarly to the hemoglobin  specific to cardiac muscle
molecule, but myoglobin requires a very low oxygen  “gold standard” for diagnosis of acute coronary
tension to release the bound oxygen. syndrome (ACS)
 as a cardiac biomarker, myoglobin has been used in o blood supply to the heart muscle is suddenly
conjunction with troponin to help diagnose or rule out an impeded
acute myocardial infarction, or heart attack  have specificity for myocardial damage
 when striated muscle is damaged, myoglobin is released  MYOCARDIAL INJURY
into the bloodstream resulting in elevated blood o An indicative when a single blood cTn measures
concentrations above the decision limit
 following an acute myocardial infarction, blood  American College of Cardiology and the European
concentrations of myoglobin elevate within 2 to 3 hours and Society of Cardiology with the National Academy of
reach peak concentrations within 8 to 12 hours. Clinical Biochemistry
 CAUSES OF MYOGLOBIN ELEVATION o Recommend to use a decision limit for myocardial
o Acute myocardial infarction injury at the 99th percentile of the reference
o Angina without infarction population for cTnT and cTnI
o Rhabdomyolysis  Laboratory should define its own cutoff value based
o Muscle trauma on its reference population and not exceed a total
o Renal failure imprecision of 10% at the diagnostic cutoff
o Myopathies  BELOW 10 ng/mL & MAY RISE TENFOLD FOLLOWING
o Vigrorous exercise AN AMI
o Intramascular injections o Normal blood concentrations of cTnI
o Open heart surgery  cTn
o Seizures(tonic-clonic) o may be ordered by itself;
o Electric shock o or in conjunction with other cardiac biomarkers:
o Arterial thrombosis  creatine kinase (CK)
o Certain Toxins  CK-MB
 Myoglobin
 most commonly used in the clinical laboratory for  cTnI and cTnT tests
myoglobin measurement o quickly replacing total CK and CK-MB
o Latex agglutination measurements
o ELISA o they are more specific to cardiac tissue and
o Immunonephelometry remain elevated in circulation for a longer period
o ECLIA of time
o Fluoroimmunoassays  blood concentrations of cardiac troponins
 qualitative spot test using immunochromatography is also o elevate: 3 to 12 hours of onset
available. o reach peak concentrations: 12 to 24 hours
o remain elevated: 1 to 3 weeks
Table No. 11.4 Causes of Myoglobin Elevations  damage to the heart was minor or that the injury took place
Acute myocardial infarction more than 24 hours in the past
Angina without infarction o CK, CK-MB, myoglobin concentrations: normal
Rhabdomyolysis o Troponin: elevated
Muscle trauma  damage to the heart likely occurred a couple of hours prior
Renal failure to the initial specimen collection and blood concentrations
Myopathies had not yet significantly elevated
Vigorous exercise o initial troponin measurement: within the
Intramuscular injections reference interval
Open heary surgery o subsequent (6- and 12-hour specimens)
troponin results: elevated
Seizures (tonic-clonic)
 symptoms are present like skeletal muscle injury
Electric shock
o CK: elevated
Arterial thrombosis
o Troponin: within the reference interval
Certain toxins
 Measured using: ELISA / immunoenzymometric assays
 Latex agglutination, ELISA, immunonephelometry, o using two monoclonal antibodies directed
ECLIA, and fluoroimmunoassays against different epitopes or;
o most commonly used in the clinical laboratory for o antigenic determinants
myoglobin measurement
 IMMUNOCHROMATOGRAPHY
BRAIN NATRIUPETIC PEPTIDE AND N-TERMINAL-
o qualitative spot test
BRAIN NATRIUPETIC PEPTIDE
 NATRIUPETIC PEPTIDES
CARDIAC TROPONIN (cTn)
o family of structurally related hormones:

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023 12
 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM
 atrial natriuretic peptide (ANP)
 B-type (or brain) natriuretic peptide
(BNP)
 Ctype natriuretic peptide (CNP)
 dendroaspis natriuretic peptide (DNP)
 B-TYPE NATRIURETIC PEPTIDES (BNP)
o produced initially as a 134–amino acid
prepropeptide
o cleaved into proBNP108- precursor molecule
stored in myocytes
o cleaved by the protease, furin, into Nterminal
(NT)-proBNP
 76–amino acid biologically inert portion
 biologically active
o a popular marker for congestive heart failure
 NT-proBNP and BNP
o found in greatest concentration in the left
ventricular myocardium
o also detectable in atrial tissue and
o the myocardium of the right ventricle
o Measured using: RIA, microparticle enzyme
immunoassay (MEIA), ECLIA
 NATRIURESIS & DIURESIS
o neurohormones that affect body fluid
homeostasis
 decreased angiotensin II & norepinephrine synthesis
o blood pressure
FIBRONECTIN
 glycoprotein composed of two nearly identical subunits
 product of a single gene
 resulting protein can exist in multiple forms due to splicing
of a single pre-mRNA
 found in plasma and on cell surfaces
 synthesized by hepatocytes, endothelial cells, peritoneal
macrophages, and fibroblasts
 FETAL FIBRONECTIN (fFn)
o used to help predict the short-term risk of
premature delivery
o produced at the boundary between the amniotic
sac and the lining of the uterus
o helps maintain the integrity of this boundary and
adherence of the placenta to the uterus
o EARLY PREGNANCY
 normally detectable in amniotic fluid and
placental tissue
o NORMAL PREGNANCY
 not detectable after 24 weeks' gestation
o Elevated fFN concentrations (22 &36 WEEKS
GESTATION)
 disturbance at the uteroplacental
junction
 increased risk of preterm labor and
delivery
ADIPONECTIN
 247–amino acid hormone
 N-terminal collagenlike domain and a C-terminal
globular domain produced by adipocytes
 exists in blood: trimers, hexamers multimer
 BMI & Adinopectin values: INVERSE CORRELATION
 Low levels of adinopectin; increase level of heart
disease, type 2 DM, metabolic syndrome, obesity
EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023
B-TRACE PROTEIN/PROSTAGLANDIN D SYNTHASE
 168–amino acid
 Low molecular-mass protein in the lipocalin protein family
 not a diagnostically efficient test for evaluation of the
glomerular filtration rate (GFR)
 promising marker in the diagnosis of perilymphatic fluid
fistulas
 BLOOD BTP MEASUREMENTS
o accurate marker of cerebrospinal fluid leakage
o potential marker in detecting impaired renal
function
 BTP SERUM VALUES; correlate with serum cystatin C,
GFR, and urine microproteins
 BTP CONCENTRATIONS
o not influenced by glucocorticoid therapy
 CYSTATIN C CONCENTRATIONS
o influenced by glucocorticoid therapy
CROSS-LINKED C-TELOPEPTIDES
 proteolytic fragments of collagen I formed during bone
turnover
 presence in serum and urine: a biochemical marker of
bone resorption
 BONE RESORPTION RATES
o Increase at menopause; elevated blood CTX
concentrations
 ANTIRESORPTIVE THERAPY (3-6 MONTHS)
o CTX concentrations drop 35% to 55%
 few limitations in measuring CTX concentrations:
o need to establish a baseline value
o variability in CTX concentrations: patient's diet,
exercise, diurnal variation
 CTX MEASUREMENTS
o cannot replace bone mineral density testing in the
diagnosis of osteoporosis
 CTX TESTING
o useful in monitoring response to antiresorptive
therapy; noninvasive and can be repeated often
 Measured using: ECLIA
CYSTATIN C
 low-molecular-mass protein with 120 amino acids
 cysteine proteinase inhibitor
 freely filtered by the glomerulus
 almost completely reabsorbed and catabolized by the
proximal tubular cells
 new sensitive endogenous serum marker for the
glomerular filtration rate; produced and destroyed at a
fairly constant rate
 may be used as an alternative to creatinine
 useful in cases where creatinine measurement is not
appropriate:
o cirrhosis, obesity, malnutrition, who have a
reduced muscle mass
 associated with an increased risk of cardiovascular
disease and heart failure in the elderly
 GFR is reduced; cystatin C & creatinine increased and
are an indication of impaired renal function
 CREATININE
o traditionally used in determinations of glomerular
function
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 [TRANS] UNIT 3: NATURAL IMMUNITY AND COMPLEMENT SYSTEM

 CYSTATIN C CONCENTRATIONS
o not affected by muscle mass, gender, age, or race
nor are they generally affected by most drugs,
infections, diet, or inflammation
o Measured using: particle-enhanced
immunoturbidimetric or
immunonephelometric methods
 CREATININE CLEARANCE TESTING
o to screen for and monitor kidney dysfunction

AMYLOID
 insoluble fibrous protein aggregates formed due to an
alteration in their secondary structure (β-pleated sheets)
 AMYLOIDOSIS
o amyloids are abnormally deposited in organs and
tissues (heart and blood vessels, brain and
peripheral nerves, kidneys, liver, spleen, and
intestines)
o causing localized or widespread organ failure
o inherited secondary to diseases that cause
overabundant or abnormal protein production,
such as:
 chronic infections, malignancies,
rheumatologic disorders
 Amyloid β42 (Aβ42) & Tau protein tests- not routinely
performed
o may be used to aid in the differential diagnosis of
Alzheimer's disease from other forms of dementia
o performed primarily in research settings on
cerebrospinal fluid
 BRAIN PHOSPHOPROTEIN
o Abnormal forms of Tau
o make up part of the structure of neurofibrillary
tangles (twisted protein fragments that clog nerve
cells)
 Aβ42- formed from β amyloid precursor protein,
o associated with the creation of senile plaques
 SYMPTOMATIC PATIENT:
o low Aβ42 concentration
o elevated Tau concentration
 indicates an increased likelihood of
developing Alzheimer's disease, but it
does not mean the patient will absolutely
develop Alzheimer's
o normal levels of Aβ42 and Tau proteins
 the cause of dementia is not likely to be
related to Alzheimer's disease

EZEKIEL CRUZ. SAMANTHA CRUZ. IVAN ILAGAN. ROMINA LASCANO. KARYLLE SURIAGA. | FEU MT 2023 14