T-cell activity in HLA-associated autoimmune diseases.

BACKGROUND: The existence of T-helper-1 (Th1) and T-helper-2 (Th2) subsets has been implicated in the regulation of several immune responses, and alterations in the Th1/Th2 balance have been involved in autoimmunity. The present study investigates the relative influence of Th1 and Th2 patterns in autoimmune responses in patients with HLA-associated autoimmune diseases. METHODS: This study concerns 849 patients of both sexes, suffering from several autoimmune diseases. Tissue typing for HLA antigens of Class I (A, B, C) and Class II (DR, DQ) was carried out in all patients by conventional serologic methods, comparing results with frequencies detected in a normal population. Many immunological tests were also done. In particular, lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg + B cells) were detected with monoclonal antibodies by a fluorescent cytometer. The changes in frequencies of T cell subsets were used to calculate the possible incidence of two effector phenotypes (TE-1; TE-2). RESULTS: The results of the immunogenetic analysis confirmed the significant HLA-associations in several diseases. The essential T-cell changes were also exposed, thus defining the incidence of T-cell phenotypes (TE-1 = 56.3%; TE-2 = 34.8%). This finding suggested a major impact of cell-mediated immunity, as compared with that of antibody-mediated immunity. CONCLUSIONS: The anomalies of Th1/Th2 balance can impact autoimmune disease, and in many cases a Th2 response can prevent Th1-mediated autoimmunity, which is the most evident phenomenon in several HLA-associated diseases.

Cytotoxic effector function in HLA-associated autoimmune diseases.

BACKGROUND: The mechanisms by which cytotoxic-T-lymphocytes (CTLs) and natural killer (NK) cells recognize and kill target cells are the subject of intense research. Previous observations in patients with HLA-associated autoimmune diseases show a major impact of cell-mediated immunity as compared to antibody-mediated immunity. This study analyzes the possible co-operation of NK cells in the autoimmune process, comparing their increase to that of cytotoxic-T-lymphocytes. METHODS: This research examines the incidence of CD8+ T cells and NK cells increases in 1065 patients with various autoimmune diseases. Tissue typing for HLA antigens was carried out in all patients by conventional serologic methods. Lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg+ B cells) were detected with monoclonal antibodies by a fluorescent cytometer. Results were statistically compared to normal control values by the Student's "t"-test. RESULTS: The analysis of results shows the incidence of CTLs and NK cell increases in patients with different autoimmune syndromes. In some diseases (uveitis, multiple sclerosis, and other neurological autoimmune disorders) raised frequencies of NK cell increase are most evident. These results suggest some possible relationships between CTLs and NK cells in the pathogenesis of the autoimmune process. CONCLUSIONS: The present results show that CTLs and NK cells are implicated in immune dysregulation, which characterizes the complex pathogenesis of autoimmune diseases.

Immunogenetics of inflammatory bowel disease.

BACKGROUND: This study investigates the association of HLA antigens to inflammatory bowel disease (IBD), which is reminiscent of the simultaneous or subsequent presence of ulcerative colitis (UC) and Crohn's disease (CD) found in these patients, showing also the concomitant association of other autoimmune conditions. The aim of this study is to confirm the autoimmune origin of IBD and the immunogenetic basis of the disease. METHODS: The study concerns 18 consecutive patients of both sexes, aged 20 to 62 years, sharing the clinical criteria of IBD indicated by previous authors. Tissue typing for HLA antigens of Class I (A; B; C); and Class II (DR; DQ) was carried out by conventional serologic methods, comparing alleles frequencies with those of normal controls random selected by the chi-square test. The main immune functions and other laboratory tests were also done in all patients, to define the concomitant autoimmune condition. RESULTS: Immunogenetic analysis shows the significant increase in two HLA antigens: HLA-DR2 (50.0% vs 25.5% of controls); HLA-DR7 (44.4% vs 21.1% of controls). In particular, the association of HLA-DR7 to IBD is reminiscent of that found in a personal series of 54 patients with primary celiac disease (55.5% vs 21.1% of controls). The findings on immune functions show the high frequency of anomalies of cell-mediated immunity (62.5%) and humoral immunity (88.8%), associated with decrease in complement and increase in immune-complexes. These alterations were always correlated with the presence of HLA-DR2 and/or HLA-DR7. CONCLUSIONS: This study on immunogenetics of ibd does not separate UC and CD on genetic grounds, thus suggesting that common HLA Class II genes may predispose to an altered regulation of immunologic mechanisms in these disorders.