Clinics in rheumatic diseases最新文献

The prevalence of the inflammatory disorders of connective tissue in the older age group is quite likely underestimated at the present time; and, in most instances, age-related factors influencing clinical expression and autoreactivity have not been intensively studied. The array of connective tissue disease that usually targets the young adult emerges in the older age group as well; and, selectively in the elderly, GCA and PMR are found. The association of malignancy with PM/DM is increased with advanced age. In view of the therapeutic implications, early diagnosis is essential, but this can be especially difficult in the setting of problems related to the ageing process.

NK cells may be important in the elimination of cells infected by virus, in the regulation of antibody production, and in tissue destruction. The significance of NK cells in rheumatic disorders is unknown, but NK cells and NK-like cells have been found in the peripheral blood and synovial tissues of patients with autoimmune disease. In particular, defects in NK cell activity have been reported in SLE, RA, PSS and SS. Of these diseases, SLE appears to be the best characterized with obvious abnormalities in NK cell numbers, impaired cytotoxicity of individual NK cells, decreased release of cytotoxic factors, deranged IFN modulation of the NK cell, and associated abnormalities in the IL-2 system. The association of these abnormalities with the underlying disease process is currently under investigation.

Patients with systemic lupus erythematosus frequently develop antilymphocyte antibodies as measured by complement-dependent cytotoxicity and immunofluorescence assays. Highest titres of both of the major IgM and IgG classes occur during phases of active disease, and their presence is associated with essentially the entire spectrum of immune system functional abnormalities in this disorder. While the full range of antibody specificities requires further clarification, antibodies to many discrete lymphocyte populations have been described, including B cells, T cells, and T cell subsets. Antibodies to T cell subsets are of special interest because of their relationship with subset depletion in vivo, and their capacity to reproduce, through effects on normal cells in vitro, the same types of immunoregulatory abnormalities characteristic of lymphocytes isolated from patients with SLE. Suppressor/inducer and suppressor/effector T cells appear to be the main targets in this regard. Antibodies specific for activated T lymphocytes exist as well, and this type has the unusual property of interfering with events operant in production of/response to interleukin-2, a critical step controlling the expansion of specifically-reactive T cells and the induction of other lymphokines. In addition to complement-mediated lysis and antibody-dependent cell-mediated cytotoxicity, anti-lymphocyte antibodies have the potential to influence immune system function by several non-cytotoxic mechanisms, including surface antigen modulation and ligand/receptor triggering. Despite the large amount of data which has been accumulated concerning the cell type specificity and functional effects of anti-lymphocyte antibodies in SLE, little is known about the nature of the surface membrane molecules with which they react. Application of cell cloning and molecular biology technology should rectify this deficiency in the near future. Although it is likely that antilymphocyte antibodies are of relevance to immune system pathophysiology in SLE, it remains to be determined whether these interesting antibodies reflect secondary events, or have some more fundamental significance.