Different modes of action of high-dose immunoglobulins in rheumatoid arthritis.
Several clinical trials have demonstrated that in patients with rheumatoid arthritis, high doses intravenous immunoglobulins (i.v.i.g.) are frequently leading to an improvement of the morning stiffness and the extra articular symptoms, as well as to a steroid-sparing effect. This i.v.i.g. therapy seems furthermore to have immunomodulatory activities in rheumatoid arthritis, since the clinical benefit is concomitant with a reduction in the number of CD4+ T-lymphocytes, with a significant dtop in the level of circulating immune complexes (CIC), and with an inhibition of the early phases of the B-lymphocytes activation. Due to the heterogeneic aspects of the rheumatoid arthritis pathogeny, it is to be expected that i.v.i.g. may interfere in different ways with many of the sequential processes in operation in the development of this disease. 1. IgGs may facilitate the reticulo endothelial clearance of inflammatory CICs by increasing their size as a consequence of the addition of exogeneous antibodies (Ab) which offers more IgG-Fc fragments as ligands for the monocytes/macrophages Fc-gamma III receptors. 2. i.v.i.g are known to down regulate the activation of B-lymphocytes and their differentiation in specialized Abs-secreting plasma-cells, and this process could affect the clones of B-cells producing anti-collagen II auto-antibodies and Abs with rheumatoid factor activity. 3. Some experimental data allow to suspect the responsibility of a super-Ag in certain forms of rheumatoid arthritis. I.v.i.g. preparations contain specific Abs which bind some of these super Ags, and impair their adequate presentation to T helper-cells. 4. Cytokines and specially the interleukin I (IL-1) which stimulates the collagenase activity, are pivotal elements in the perpetuation of the inflammatory connective tissue damages in rheumatoid arthritis. I.v.i.g. preparations contain soluble cytokine-receptors, as well as anti-IL-1 and IL-6 specific Abs which both act as cytokines agonists and sustain the effective antiinflammatory action of high-dose polyclonal IgGs. Although more clinical data are still needed to sustain the routine use of i.v.i.g. in rheumatoid arthritis, the efficacy of this therapy is not disputable any more in other pathologies with similar immunological disorders.
Delire
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Clinical research Immunology, Behringwerke AG, Marburg, Germany.
D000328:Adult; D001171:Arthritis, Juvenile / Q000276:immunology / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D012157:Mononuclear Phagocyte System / Q000276:immunology; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D018089:Superantigens