Increased T-lymphocyte apoptosis/necrosis and IL-10 producing cells in patients and their spouses in Icelandic systemic lupus erythematosus multicase families.
The objective of this study was to evaluate apoptosis and production of IL-10 in SLE patients, their spouses and first-degree relatives in Icelandic SLE multicase families. Previously, increased IL-10 production has been found in all three groups. As IL-10 has been found to induce apoptosis in SLE, the percentage of lymphocytes undergoing apoptosis was evaluated, as well as the possible correlation between apoptosis and IL-10 production. Apoptosis and IL-10 production were studied in SLE patients (n = 12) from SLE multicase families and their spouses (n = 12) and a matched control group of healthy individuals (n = 10). The proportion of T and B lymphocytes undergoing apoptosis at 0, 24, 48 and 72 h was detected by flow cytometry using Annexin V and PI staining and the rate of apoptosis was calculated. IL-10 production was studied simultaneously by ELISpot analysis of freshly isolated peripheral blood mononuclear cells. In addition, T lymphocyte apoptosis at t = 0 was investigated in a group of non-household first-degree relatives (n = 10) and controls (n = 10). Antinuclear and antilymphocyte antibodies were analysed in all the groups. The SLE patients as a group had a significantly increased percentage of T lymphocytes in apoptosis at 0 and 48 h and a significantly higher number of IL-10 producing cells as compared with the healthy controls (P = 0.03, 0.02 and 0.03, respectively). The spouses also had significantly increased percentage of T lymphocytes in apoptosis (t = 0) and a significantly higher number of IL-10-producing cells when compared with healthy controls (P = 0.01 and 0.02, respectively). There were no significant differences between the patients and their spouses. For apoptosis of B lymphocytes no difference was found between the groups. The SLE patients as a group had the highest rate of apoptosis. No correlation between the degree and rate of apoptosis and the number of IL-10-producing cells was detected. The first-degree relatives did not have increased percentage of T lymphocytes undergoing apoptosis at t = 0 compared with healthy controls. The SLE patients had higher titres of ANA compared with the other groups. No correlation was detected between the ANA titre and the percentage of lymphocytes undergoing apoptosis. There was no correlation between disease activity as measured by SLEDAI and apoptosis. In conclusion, our results suggest that environmental factors common to both SLE patients and their spouses are associated both with the increased apoptosis and increased spontaneous production of IL-10, thus providing support for the notion that both environmental and genetic factors influencing apoptosis are of importance for the development of SLE.
Department of Internal Medicine, Division of Rheumatology and Center for Rheumatology Research, Landspitalinn, Reykjavik, Iceland. gerdurgr@landspitali.is
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Gröndal
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Traustadottir
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Kristjansdottir
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Lundberg
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Klareskog
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Erlendsson
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Steinsson
D000974:Antibodies, Antinuclear / Q000097:blood; D000961:Antilymphocyte Serum / Q000097:blood; D017209:Apoptosis; D005192:Family Health; D005260:Female; D006801:Humans; D007055:Iceland; D016753:Interleukin-10 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D000974:Antibodies, Antinuclear; D000961:Antilymphocyte Serum; D016753:Interleukin-10