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S100 proteins
 Low molecular weight proteins
 Ca⁺² -binding capacity
 More than 20 members (chromosome 1q21)
 Members of innate immunity of airways
epithelium:
➢ Against microbial peptides.
➢ Proinflammatory agents.
• Inflammatory, rheumatic and neoplastic
disorders.
• Role in pathogenesis of CRSwNP ?????
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S100 proteins (Cont.)
 Monomers (α or β subunits), homodimers or
heterodimers .
 S100A8 and S100A9 are special (S100A8/A9,
calprotectin)
 Receptors: RAGE, TLR and G-protein coupled
receptors.

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S100 proteins (cont.)
➢ Functions:
✓ Cellular growth, migration and differentiation,
✓ Ca⁺² homeostasis
✓ Apoptosis
✓ DNA repair
✓ Enzyme activation
✓ Protein phosphorylation
✓ Protection from oxidative cell damage
✓ Act as biomarkers for specific tumors and
diseases.

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Our study
❖Changes in levels of S100 proteins in CRSwNP compared
to control patients.

❖Confirm the relation between S100 proteins and polyp


formation in CRSwNP.

❖ELISA and immuno-histochemistry (IHC).

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Patients and methods
❖40 Patients

❖18 to 59 years.

❖Two groups:
1- Control group: 20 patients without symptoms or signs
of allergy or CRS and undergoing nasal surgeries.
2- CRSwNP group: 20 patients with nasal polyposis.

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Patients and methods (cont.)
❖Exclusion criteria:
1- Steroids usage (local -Systemic ).
2- Prior surgery in the nasal cavity.
3- CRS without polyposis.
4- HBV, HCV or HIV (change levels of S100 expression)

❖ Specimens:
1. Control: one specimen (nasal mucosa of middle
meatus)
2. CRSwNP: two specimens (polyp tissue & nasal
mucosa of middle meatus).
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Results
❖ELISA
S100 Concentration (pg./gram)
4500
4000
ρ < 0.001
3437.9
3500
3000
2513.85
2500
2000
1500
1000
500
0
polyp control
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❖ELISA
Results (cont.)
S100 Concentration (pg./gram)
5000

4500 ρ < 0.001


3969.55
4000

3500

3000
2513.85
2500

2000

1500

1000

500

0
Nasal mucosa Nasal mucosa
(CRSwNP) (control) 10
Results(cont.)
❖ELISA
5000 S100 Concentration (pg./gram)
4500

3969.55 ρ = 0.010
4000

3500
3437.9

3000

2500

2000

1500

1000

500

Nasal mucosa Polyp


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Results (cont.)

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Results (cont.)
❖IHC staining (control)

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Results (cont.)
❖IHC staining (CRSwNP polyp tissues, hyperplastic and
oedematous).

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Results (cont.)
❖IHC staining (CRSwNP mucosa of middle meatus).

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Conclusion
❖S100 proteins are minimally expressed in normal nasal
epithelium.

❖Levels are significantly increased in mucosa and polyp


tissues of CRSwNP.

❖Suggested mechanisms:
1. Influx of inflammatory cells (mainly eosinophils).
2. S. aureus bacterial biofilm in most CRSwNP
patients (homodimeric S100A8 and S100A9).
3. Released S100 proteins act as danger molecules.

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Future considerations
❖Further studies on S100 proteins ???
➢ Which family member
➢ Exact mechanism of action.
❖S100 neutralizing antibodies in cancer cells studies:
reduction of cellular proliferation and migration.
❖S100 neutralizing antibodies on pathogenesis of
CRSwNP ????
❖New treatments:
1. Redefine the treatment regime.
2. Prevent recurrence .

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thank you

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