Decreased CD22 expression and intracellular signaling aberrations in B cells of patients with systemic sclerosis

• Published in: Rheumatology international Vol. 38; no. 7; pp. 1225 - 1234
• Main Authors: Melissaropoulos, Konstantinos, Liossis, Stamatis-Nick
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2018; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD19; B-Lymphocytes - metabolism; Female; Humans; Lymphocyte receptors; Male; Medicine; Medicine & Public Health; Middle Aged; Observational Research; Phosphorylation; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - physiology; Rheumatology; Scleroderma; Scleroderma, Systemic - genetics; Scleroderma, Systemic - metabolism; Sialic Acid Binding Ig-like Lectin 2 - metabolism; Signal Transduction; Systemic sclerosis; T cell receptors; Lyn; B cell; Systemic sclerosis; CD19; CD22
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-018-4076-3

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.