ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2193

Altered Apoptosis Profile and Associated Soluble Factors In Patients With Juvenile-Onset Systemic Lupus Erythematosus

Bernadete Liphaus1, Maria H. B. Kiss1, Solange Carrasco2 and Cláudia Goldenstein-Schainberg3, 1Pediatria, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil, 2University of São Paulo, São Paulo, Brazil, 3Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

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.

Disclosure:

B. Liphaus,
None;

M. H. B. Kiss,
None;

S. Carrasco,
None;

C. Goldenstein-Schainberg,
None.

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