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Although the pathophysiology of systemic sclerosis (SSc) is not fully clarified, there are considerable data implicating abnormalities of microvascular changes, fibroblast activation and immune system abnormalities. Immune system activation may play a part as a stimulus in both fibrotic and vascular damage.1 To investigate the immune system abnormalities in the pathogenesis of SSc we evaluated lymphocyte phenotypes in patients with SSc and healthy controls by flow cytometry (Epics Profile II) for total T (CD3), T helper (CD4), T supressor (CD8), B lymphocyte cell surface marker (CD19), activation marker (CD25) and natural killer (NK) cell surface marker NKH-1 (CD56).
We studied 29 patients (27 women, two men) 16 limited, 12 diffuse and one overlap who fulfilled preliminary criteria for classification of SSc.2 Anti-nuclear antibody was positive in 25 (86.2%) and anti-Scl70 antibodies was positive in seven (24.1 %) patients. The age range of the patients was 20–63 years (mean (SEM) 40 (5)) and the mean (SEM) disease duration was 5.6 (5.5) years. Patients were receiving no medication nor had received any immunsupressive agent for at least three months. Controls were 12 age and sex matched healthy volunteers with an age range from 27–51 years.
Data were compared for significance for Student’s unpaired t test.
Table 1 summarises lymphocyte phenotypes in patients with SSc and healthy controls.
We found a higher expression of T cell activation marker CD25+ and NK cell main surface marker CD56+. In lymphocyte phenotypes there was not any difference among disease subsets and CD25+ and CD56+ were not correlated with the disease duration.
Immune system abnormalities have been suspected in the development of SSc because of the presence of autoantibodies, changed cytokine production and evidence of overlap with other autoimmune diseases. It was suggested that immune system changes play the major part in the development of vasculopathy and fibrosis.3 Previous reports on T lymphocyte subpopulations in SSc are partially conflicting. Melendro et al 4demonstrated that there was no significant difference in the levels of CD4+ and CD8+ among 22 SSc patients and control group but in rheumatoid arthritis (RA) CD3+ and CD8+, in Sjögren’s syndrome CD3+, CD4+ and CD8+ levels were significantly decreased compared with those of controls and they suggested that the abnormalities in immune regulatory T cell circuits leading to autoimmunity are different in each connective tissue disease.
Whiteside et al 5 and Barrett et al 6 by using the indirect immunoflourescence method, reported that CD8+ supressor/cytotoxic T cells are decreased in SSc group, our findings differ from those of Whiteside and Barrett; we and Degianniset al 7 have used the more sensitive flow cytometry method and could not find any difference between T lymphocyte subgroups of SSc patients whereas in the pathogenesis of SSc the role of CD4+ and CD8+ T lymphocytes is still obscure. Presence of autoantibodies and hypergammaglobulinaemia support the role of humoral immunity but B lymphocytes were rarely found in the skin biopsy specimens.8 CD19+ is a cell surface marker of B lymphocytes and we could not observe any difference in the levels of CD19+ thus we can say that B lymphocytes might play only a minor part in the pathogenesis of SSc. CD25+ is one of the subunits of high affinity IL2R and known as the alpha chain of IL2R. Brunset al 9 established a clear correlation between CD25+ and soluble IL2R in serum. T lymphocytes expressing CD25+ and T helper cell derived cytokines and growth factors stimulate matrix protein synthesis by fibroblasts, resulting in generalised fibrosis and sclerosis. In our study we found significant increases of CD25+ and this surface marker can be used in the follow up the inflammatory stage and activity of SSc. In further studies the investigation of CD25+ T cell subsets CD4 , CD8, TCR gamma–delta and other T cell activation markers HLA-DR, CD45RO/CD45RA will be useful to shed light on the pathogenesis of SSc. NK cell abnormalities have been described in a number of rheumatic diseases such as RA, Sjögren’s syndrome, systemic lupus erythematosus. NK cells are large granular lymphocytes easily identified morphologically by the presence of azurophil granules in their cytoplasm and they commonly express certain cell surface markers such as CD16+ and CD56+; CD56+ is a homofilic adhesion molecule that belongs to the immunglobulin superfamily. NK cells are the main cellular effectors of antibody dependent cell cytotoxicity, they mediate antigen presentation and secrete immune modulator cytokines like interferon, IL2, colony stimulating factor, these functions suggested the involvement of NK cells in the pathophysiology of SSc.6 10
We found the percentage of CD56+ significantly higher in SSc patients (mean (SD) 22 (9)) than controls (mean (SD) 14 (5)). Although this finding suggested the role of CD56+ cells in the pathogenesis of SSc, various results in different investigations pointed out that further investigations on CD56+ and CD16+ NK cell percentage and activity are needed.
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