ALTERED IMMUNITY IN CIRCULATION OF PATIENTS WITH IGA NEPHROPATHY

Several abnormalities of the immune system are assumed to be involved in the development of IgA nephropathy (IgAN). The roles of cytokines a nd other soluble factors, which may interact. mutually in peripheral c irculation, have been studied by many investigators who believed that analysis of the source and function of such factors might provide a si gnificant clue in order to disclose the mechanisms of development of I gAN. Changes in B cell immunity such as enhanced production of IgA or IgE have been reported in IgAN. B cells in IgAN also showed enhanced e xpression of CD23 (Fc epsilon RII) on their surface. Th2 cell derived pleiotropic cytokine, interleukin (IL)-4 is known as potent inducer fo r CD23, IgE and IgA. In IgAN, synthesis of IL-4 is enhanced both in vi vo and in vitro. Th-1 derived cytokine, interferon (IFN)-gamma is a an tagonist to Th-2 derived cytokines. Although, in vitro synthesis of th e cytokine is unexpectedly increased in IgAN, its suppressive effects against IL-4 are, at least partially, impeded in IgAN. Under this cond ition, relatively enhanced Th-2 like cell activity may help to keep B cell activation in IgAN. Increased numbers of human leukocyte antigen (HLA)-DR bearing natural killer (NK) cells are observed in IgAN. These HLA positive NK cells simultaneously express high IFN-gamma genes. Th ese NK cells are possibly the source of increased IFN-gamma in IgAN an d play a compensatory roles for suppressed Th-1-like cells. Interferon -gamma production by NK cells in IgAN is probably regulated by IL-12. Although the source of IL-12 in circulation has not been determined, c haracteristically activated B cells in IgAN, other than macrophages, m ay have some relation to this IL-12-NK-IFN-gamma cascade. The HLA-bear ing rate of NK cells in IgAN showed a positive relation to rapidity of progression of renal dysfunction in a long-term follow-up study. Thes e findings suggested that IgA specific changes in peripheral cell inte raction involving Th-2-like cells, B cells, macrophages and NK cells m ay be able to induce local inflammatory events in the kidneys.