Clinics in Immunology and Allergy最新文献

Lupus nephritis is composed of a continuum of clinical and morphological features. The World Health Organization classification delineates categories of lupus nephritis which have some unique characteristics. However, its utility for assessing prognosis and indications for treatment can be enhanced by supplementary description of activity and chronicity features of the renal pathology.

The prognosis of all forms of lupus nephritis has improved over the past several decades as a result of improved ancillary medical therapies and more effective immunosuppressive regimens. Some patients with active lupus nephritis may respond dramatically and completely to high-dose prednisone. More commonly, such therapy achieves incomplete responses and disposes patients to a high probability of progressive renal scarring and a substantial risk of end-stage renal failure. Conventional cytotoxic drug therapy with azathioprine or cyclophosphamide reduces the likelihood of unfavourable renal outcomes, but this advantage is offset by a number of potentially serious side-effects. Intermittent pulse cyclophosphamide treatment produces the lowest risk of renal failure and appears to have a substantially reduced rate of toxicity.

The expression of class II, and even of class I, MHC products in many sites in normal kidney may be low enough to be rate-limiting for antibody-mediated or T cell-mediated injury involving these structures (e.g. rejection). In certain human diseases and in experimental animal models, renal expression of class I and II MHC antigens is capable of large quantitative changes accompanied by shifts in sites of expression. These alterations may be induced by local or systemic processes, and can at times be controlled or reversed by pharmacological intervention (e.g. cyclosporin). The interferons, especially γ-interferon, are probably involved in these changes, but many other influences may also participate. The study of MHC induction may prove to be useful in the clinical and pathological assessment of renal disease, and in understanding the pathogenesis of some forms of renal injury, such as rejection and interstitial nephritis. At present, further studies are needed to unravel the significance of these changes.

There is good evidence that glomerular injury may be related to many infectious agents in both experimental animals and in man, generally through an immune complex mechanism. Whether these infectious agent antigens are ’planted’ or within a deposited, previously circulating, immune complex is not known. The two mechanisms are not mutually exclusive. New concepts of a dynamic and constantly fluctuating involvement of immune reactants in the production of glomerular inflammation have received considerable emphasis.

Ideally, to manage postinfectious glomerulonephritis, one should eradicate the involved antigen(s) or inhibit production of specific antibody. A rapid and complete healing is usually observed in acute postinfectious glomerulonephritis characterized by proliferation and humps. Recovery after treatment is also possible in a few other situations, i.e. glomerulonephritis secondary to infective endocarditis or to infection of a ventriculoatrial shunt and glomerulonephritis associated with congenital and secondary syphilis.

Unfortunately, in most varieties of glomerulonephritis, as yet unexplained immune mechanisms of glomerular injury interfere so that spontaneous recovery of the infection does not always result in clinical improvement and resolution of the immune deposition. Moreover, the treatment of patients by specific therapy as well as with combinations of steroids and immunosuppressive agents does not appear to change the course of the disease. It seems that, once the clinical picture is manifested, mechanisms of glomerular damage are triggered and continue independent of the infective organism. The introduction of appropriate vaccines should reduce the frequency of postinfectious glomerulonephritis.

IgA nephropathy (IgAN), also called mesangial IgA glomerulonephritis, occurs most frequently in three clinical conditions: as an idiopathic nephritis in Berger’s disease, and as a secondary disease in Henoch-Schönlein purpura (HSP) and liver cirrhosis. In this paper, clinical and biological facts related to these conditions are reviewed. Known animal models reproducing immunohistological lesions of IgAN are described. The numerous aspects of this syndrome still unclear are then evoked and discussed: clinical and biological puzzles as well as equivocal epidemiological or genetic features. Finally, the small arsenal of therapeutic weapons which can be used as a cure or as prevention is depicted.