Case Study: “X-linked Agammaglobulinemia”

1. Bill was well for the first 10 months of his life. State a plausible explanation for this. Be specific.
Generally, infants are protected after birth due to maternal IgG and antibodies being transferred
via passive immunity from mother to child. Infants are still developing their immune systems
during this time and the mother’s passing her antibodies to the child will provide coverage to
make up for the lack of immune response in the infant. Bill’s condition started to deteriorate at
around 10 months since maternal antibodies and maternal IgG start to decrease and thus have a
lessened effect towards immune response. As a result, after 10 months, Bill started to see
symptomology of recurrent infections. (Textbook, Previous Knowledge)
2. Based on information in the case study, state one reason why specific immunity diminishes in
senior citizens.
Specific immunity diminishes in senior citizens as B cells are produced at a lesser rate. The
process of B cell maturation is quite intensive and the process of their maturation as well as the
overall quantity decline with age. Furthermore, B cells produce antibodies, specifically
immunoglobulins with specificity to antigens as a part of the adaptive immune system response.
If the quantity of B cells diminishes with age, then so do the number of circulating
immunoglobulins and thus specific immunity diminishes with age. (Case Study)

3. What laboratory test results indicate that Bill has no B-cells?

Flow cytometry tests would indicate lymphocytes with the CD19 marker. This marker
distinguishes B Lymphocytes from other lymphocytes. None of Bill’s lymphocytes would react
with a CD-19 antibody which would indicate the absence of B cells. (Case Study)

4. Based on information in the case study, what is Bill’s brother John’s likely diagnosis? Why?
(State all the reasons you suspect this Dx.)
More than likely, Bill’s brother John also had X-linked Agammaglobulinemia. The reasons for
suspecting such would include a serum level of IgG like Bill. Additionally, recurrent infections of
pneumonia would also be associated with XLA. Like Bill, John is around the same age that Bill
started to develop atelectasis and a chronic cough. John is also a male and since XLA is X-linked,
it can be assumed that John also received the defective BTK gene located on X chromosome
Xq22 from their mother. Since there mother is a carrier, there is a 50% chance that her male
children will have XLA. (Case Study)
5. Does Bill’s innate immune system appear to be normal? What lab results support your answer?
Bill’s innate immune system appears to be normal and functioning. The lab results that are used
to support this would be normal white blood cell count denoting that neutrophils, lymphocytes,
monocytes, and eosinophils were in appropriate percentages. As such, the innate immune
response would be comprised of monocytes, macrophages, NK cells, Neutrophils, Mast cells,
dendritic cells, Eosinophils and Basophils as they have a nonspecific response to foreign
antigens. Due to the normal levels of these WBC’s, it can be assumed that Bill’s innate immune
system function was normal. (Case Study)

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 6. What are the ‘gamma globulins’ found after immuoelectrophoresis? Where does the name
‘gamma globulin’ originate? [Internet]
The gamma globulins found after immunoelectrophoresis would be IgG, IgA, IgM, IgE, IgD.
Gamma globulins were named such as they were globe shaped proteins with a higher molecular
weight that albumin. These globulins would be differentiated into 4 different categories or
fractions using serum protein electrophoresis (SPE). SPE separates these proteins through
applying electricity to a gel medium. The net charge that is present on a protein or globulin will
allow it to migrate. Gamma globulins migrate mainly in the “Gamma” fraction/region.
Source: https://www.ncbi.nlm.nih.gov/books/NBK204/
7. What is ‘Immune Globulin’, which is used in intravenous therapy? [Internet]
Therapeutic immunoglobulin is derived from a pool of various donors. The donations of blood
will have a portion of IgG present which can be separated and then pooled together. This pool of
immunoglobulin can then be administered as replacement therapy to those that are
immunodeficient such as those with XLA. Administration via IV would have to occur every 3 rd or
4th week to replenish or replace the patient’s current dose.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324501/
8. Name 3 situations other than XLA where Immune Globulin is administered. [Internet]
1) Common Variable Immunodeficiency
a. Hypogammaglobulinemia would lead to low levels of immunoglobulins.
b. Immune Globulin administration would bring these levels back to normal thus
increasing immune function.
2) Specific antibody deficiency
a. Normal levels of IgG, IgA, IgM, IgG but IgG antibodies do not respond well to certain
vaccines.
b. Immune Globulin administration would help immune systems build immunity to
certain vaccines if such a vaccine was previously administered and recurrent
infections antithetical to the vaccine administered to combat that infection are
proven ineffective.
3) Hyper IgM Syndrome
a. Defective CD40L and CD40 interactions lead to impaired isotype switching, high
amounts of IgM are produced meanwhile other isotypes are low in quantity if not
completely absent.
b. Immune Globulin administration for those with Hyper IgM syndrome is indicated to
help assist with decreasing infection severity and recurrence as administration
would replenish and increase quantity for other immunoglobulin isotypes to combat
infections.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324501/

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