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High levels of circulating B1a lymphocytes expressing CD5 have been reported in some patients with non-organ-specific autoimmune diseases, such as systemic lupus erythematosus, primary Sjögren’s syndrome, and rheumatoid arthritis, although CD5+ B cells do not seem to be only agents of autoantibody production.1 Thus, B cells display a variety of characteristics other than antibody production—for example, in lymphoid architecture development, regulation of T cell subsets and antigen presenting cell function through cytokine production, and in activation of T cells.2,3 In addition, CD5+ B cells have a role in several organ-specific autoimmune diseases, such as chronic urticaria,4 insulin dependent diabetes mellitus,5 myasthenia gravis,6 and immune thrombocytopenic purpura, where the increased proportion of CD5+ B cells in spleen and peripheral blood, and their ability to produce antiplatelet antibodies, indicates that they are directly involved in the pathogenesis.7 Furthermore, Liversidge et al isolated CD5+ B lymphocytes and TCR γ-δ T lymphocytes from the vitreous humor of a patient with acute sympathetic ophthalmitis8; Sampalo et al found a correlation between CD5+ B cells and HIV disease progression9; and Printz et al discovered that a subset of patients with schizophrenia had raised levels of CD5+ B cells, which provides evidence suggestive of autoimmune manifestations in schizophrenia.10
Uveitis is a general term denoting any type of intraocular inflammatory disease, which may be of unknown origin or associated with many general diseases.11–14 Although immunological disturbances play a part in the pathogenesis of uveitis, it is still difficult to understand the mechanism by which tissue damage is mediated; further research is needed.15 Since 1989 the uveitis unit of our hospital has comprised an interdisciplinary team of internists and ophthalmologists studying the cause of uveitis in patients with uveitis of unknown origin. By 2000 we had prospectively studied 315 patients with uveitis, none of whom had been previously diagnosed with systemic diseases which might have been caused by uveitis. We aimed at evaluating the average level of CD5+ B cells in peripheral blood from 27 patients with idiopathic uveitis (20 with anterior uveitis, seven, with posterior uveitis) and 21 healthy subjects matched for age and sex who served as control group. Patients were consecutively enrolled between May 1999 and November 2000, and the control group was recruited from the hospital staff. Double labelling with CD5 and CD19 monoclonal antibodies (BD Oncomark CD5 FITC/CD10 PE/CD19 perCP-Cy5.5; Becton Dickinson, California, USA) was used for lymphocyte staining. The flow cytometry analysis was carried out with a FACScan cytometer. Statistical analysis was performed with a t test for independent continuous variables and Fisher’s exact test for categorical variables.
The mean (SD) level of CD5+ B cells in peripheral blood was found to be significantly higher in the 27 patients with uveitis (91 (76) cells×106/l; percentage 28 (20)) than in the control group (58 (34) cells×106/l; percentage 18 (5)); p<0.05). Moreover, we also found increased levels of CD5+ B cells in various subgroups of uveitis—namely, anterior uveitis (94 (79) cells×106/l; percentage 29 (19)) and clinically severe cases of uveitis (108 (93) cells×106/l; percentage 34 (21)), which were significantly different from those in control subjects (p<0.05). However, no significant differences were found between anterior and posterior uveitis subgroups, or between unilateral and bilateral disease, or between single and repeated episodes of inflammation.
Thus, CD5 + B cells may lead to uveitis by acting as antigen presenting cells, stimulating CD4+ T cells with an unknown antigen. Patients with non-organ-specific and organ-specific autoimmune diseases, such as uveitis, may have increased levels for CD5+ B cells, which indicates an immunoregulatory role of CD5+ B cells in autoimmunity, and suggests that effective ways of testing and controlling the immune response in patients with uveitis might be devised.
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