Increased T-lymphocyte apoptosis in lupus correlates with disease activity and may be responsible for reduced T-cell frequency: a cross-sectional and longitudinal study.
Apoptosis of lymphocytes is increased in patients with lupus. This may be pathogenic leading to increased load of autoantigens or may be a bystander effect of immune activation. A major unresolved issue is whether apoptosis is related to disease activity. Also its association with lymphocyte frequencies, anti-nucleosomal antibodies and serum IL 10 levels needs to be explored further. The aims of this study are to measure T- and B-lymphocyte apoptosis in patients with lupus and look at the effect of disease activity in a cross-sectional and longitudinal design and to determine frequency of T and B cells, level of anti-nucleosomal antibodies and serum IL 10 and assess their relationship with apoptosis. This study included 41 patients with SLE and 20 controls. A cutoff value of 4 in systemic lupus erythematosus disease activity index (SLEDAI) was used to separate active from inactive SLE. The frequency and degree of apoptosis of T and B lymphocyte were enumerated by flow cytometry using peripheral blood mononuclear cells (PBMCs) stained with CD3/CD19 and annexin V/PI. The data for T/B cell frequency are represented as % of these cells in the PBMC population, whereas percentage of apoptotic cells is out of total T or B cells. Serum anti-nucleosomal antibodies and IL 10 were assayed using ELISA. A repeat assessment of these parameters was carried out in 11 active patients when they became inactive. We found higher T-lymphocyte apoptosis in patients with SLE versus controls (14.8 +/- 9.2, 7.2 +/- 3.0; P < 0.05) and a lower frequency of T cells (72.7 +/- 12.6, 79.9 +/- 5.8; P < 0.05). T-lymphocyte apoptosis was higher in patients with active disease compared with inactive (18.5 +/- 11.3, 11.6 +/- 5.4; P = 0.05). Further, T-lymphocyte apoptosis directly correlated with SLEDAI (r = 0.37, P < 0.05) and inversely with T-cell frequency (r = -0.29, P < 0.05). Anti-nucleosomal antibodies correlated with SLEDAI but not apoptosis. On longitudinal follow-up, a decline in T-cell apoptosis was seen in patients with SLE, however this was not statistically significant. We confirmed a higher degree of apoptosis in T-lymphocytes in patients with SLE and found a direct correlation of T-cell apoptosis with disease activity. Patients had reduced T-cell frequency, which inversely correlated with T-cell apoptosis and may suggest a cause-effect relationship.
Dhir
V
V
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Singh
A P
AP
Aggarwal
A
A
Naik
S
S
Misra
Ramnath
R
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000473:pathology*; D008297:Male; D009707:Nucleosomes / Q000276:immunology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
D000888:Antibodies, Anti-Idiotypic; D009707:Nucleosomes; D016753:Interleukin-10