Decreased CD22 expression and intracellular signaling aberrations in B cells of patients with systemic sclerosis
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The objective of the study was to explore the phenotype and intracellular signaling events of B cells in patients with systemic sclerosis (SSc). Peripheral blood B cell surface markers CD19 and CD22 were evaluated by flow cytometry in 23 patients with SSc and seven healthy individuals. Levels of intracellular kinases Lyn, Syk and P-Y 348 Syk along with phosphatase SHP-1 were examined with Western immunoblotting in selected patients. P-Y 822 CD22 was subsequently evaluated flow cytometrically in antigen receptor stimulated B cells. A statistically significant decrease in CD22 B cell surface expression was found in the diffuse subset of patients (median CD22 MFI ± SD was 5.90 ± 2.35 vs 10.20 ± 1.88 for patients vs healthy controls respectively; p = 0.021), while no statistically significant change was found regarding CD19. CD22 underexpression was more pronounced when interstitial lung disease (ILD) was present (median CD22 MFI ± SD was 5.90 ± 2.25 vs 10.20 ± 1.88 for patients with ILD vs healthy controls respectively; p = 0.011). CD22 phosphorylation following B cell receptor (BCR) stimulation was also found to be impaired in patients with diffuse SSc (median change in MFI ± SD was 0.28 ± 0.09 vs 0.38 ± 0.08 for patients vs healthy controls respectively; p = 0.034). Low CD22 expression was arithmetically correlated with kinase Lyn underexpression (Pearson coefficient 0.926; p = ns) in B cells from a small sample of patients. These results suggest that CD22 underexpression and impaired phosphorylation along with implications for Lyn kinase aberrations could contribute to the activated B cell phenotype in SSc.
KeywordsB cell Systemic sclerosis CD22 CD19 Lyn
We would like to thank all study participants. We would also like to thank Eugenia Verigou, MD, for her valuable contribution regarding the flow cytometry experiments and figures.
KM designed the study, performed patient recruitment, performed flow cytometry and western immunoblotting experiments, analyzed the data and drafted the manuscript. SNL conceived the study concept, designed the study, participated in patient recruitment, data analysis and manuscript drafting and revision. All authors read and approved the manuscript.
This work was supported by the University of Patras through the “Karathodori” research grant and the Hellenic Rheumatology Society through a scholarship.
Compliance with ethical standards
Conflict of interest
All authors declare no conflict of interest.
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