Session Title: Pediatric Rheumatology - Pathogenesis and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Apoptosis has been demonstrated to be involved in immune dysregulation and development of adult systemic lupus erythematosus (SLE) but less is known about its relevance in juvenile-onset SLE (JSLE). Therefore we aimed to assess a panel of apoptosis related proteins in patients with JSLE and their possible relationship with disease activity.
Methods: Forty-three JSLE patients (36F:7M, mean age=14.3 yrs, revised ACR criteria), 30 with active disease (SLEDAI score ³ 4), and 35 age and gender matched healthy controls were studied. After staining with specific moAbs, Fas and Bcl-2 expressions in peripheral B and T lymphocytes and monocytes were analyzed by flow cytometry. Soluble sera molecules (sFas, sFasL, sTRAIL and sBcl-2) were measured by commercial ELISA kits. Statistical analysis used Kruskal-Wallis test and Spearman’s rank, with P value < 0.05 considered significant.
Results: JSLE patients compared to controls had significant increased Fas expression on CD3+ (43.7±10.3 vs. 28.9±9.4%, p<0.01), CD4+ (20.3±6.7 vs. 16.2±6.2%, p<0.05) and CD8+ (21.5±9.6 vs. 12.3±5.8%, p<0.01) T cells, and on CD19+ B cells (2.1±1.4 vs. 1.4±0.7%, p<0.05), whereas, it was decreased on CD14+ monocytes (93.6±6.9 vs. 96.7±2.5%, p=0.01). Percentages of CD19+Fas+ cells were positively correlated with SLEDAI (r=0.38, p=0.02) and an inverse correlation was observed for percentages of CD14+Fas+ cells and SLEDAI (r= -0.55, p=0.01). Mean fluorescence intensity (MFI) of Bcl-2-positive cells from JSLE patients was significantly increased in CD3+ (28.8±8.4 vs. 22.9±4.2%, p<0.01), CD4+ (28.6±8.2 vs. 22.9±4.4%, p<0.01) and CD8+ (29.4±9.4 vs. 22.8±3.6%, p<0.01) T cells, and also in CD19+ B cells (25.5±9.6 vs. 21.5±3.6%, p=0.06). Bcl-2 expression in CD14+ monocytes was lower in JSLE compared to controls (25.2±18.2 vs. 34.5±16.6%, p=0.006). Direct correlation between percentages of CD19+Bcl-2+ cells and SLEDAI (r=0.47, p=0.04) was shown. JSLE patients had significantly increased sFas (188.1±69.2 vs. 133.2±80.6pg/ml, P<0.05) and sTRAIL (691.3±631.8 vs 346.6±251.1pg/ml, P<0.05), decreased sFasL (0.08±0.1 vs. 0.36±0.4ng/ml, P<0.05), and similar sBcl-2 (7.4±8.6 vs. 9.3±9.6mg/ml, P<0.05) levels compared to healthy controls. SLEDAI score directly correlated with sFas (r=0.52; p=0.001).
Conclusion: The present study demonstrated that dysregulation of apoptosis pathways and associated soluble factors underlie JSLE pathogenesis, particularly during active disease. A role for CD19+Bcl-2+ cells and/or sFas as a marker of disease acitivity in children deserves further investigation in prospective studies.
M. H. B. Kiss,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-apoptosis-profile-and-associated-soluble-factors-in-patients-with-juvenile-onset-systemic-lupus-erythematosus/