Immune nephropathies

The last three years have expanded insight as to how lymphocytes respond to antigens or xenobiotics, and also the knowledge of the pathophysiology of renal diseases. This provides new clues on the mechanisms by which chemically induced immune responses trigger kidney lesions. First, we will discuss the general mechanisms that could be responsible for drug-induce immune nephropathies. The role of Thl and Th2 CD4+ T-cell subsets in the development of nephropathies will be also debated. Then, we will describe the types of immune nephropathy than can be induced by xenobiotics in patients. Finally, we will focus on experimental models of chemical-induced systemic... 

Pestka, J. J. Deoxynivalenol-induced IgA production and IgA nephropathy-aberrant mucosal immune response with systemic repercussions. Toxicol. Lett. 140-141, 287, 2003. 

Idiopathic membranous nephropathy is the commonest form of nephrotic syndrome in middle-aged and elderly patients. The glomerular capillary wall is thickened due to immune deposits (containing mosty immunoglobulin G, IgG)... 

Roccatello D, Picciotto G, Ropolo R, et al. Kinetics and fate of IgA-IgG aggregates as a model of naturally occurring immune complexes in IgA nephropathy. Lab Invest 1992 66(l) 86-95. 

Membranous nephropathy is rare and causes the nephrotic syndrome, usually with minimal-change glomerulopathy, with or without interstitial nephritis (SEDA-11, 85). A retrospective study provided more data on the frequency and clinical characteristics of membranous nephropathy associated with NSAIDs (158). It confirmed that it is rare (13 of 125 patients diagnosed during the last 20 years met the strict criteria for NSAID-associated membranous nephropathy), and the nephrotic syndrome is reversible after prompt withdrawal. The pathogenesis is unknown but seems to be immune-mediated, given the characteristic deposition of IgG and C3. 

An experimental model of metal-induced autoimmunity and nephropathy has been developed in the BN rat, which is genetically predisposed to develop Th2-type of immune response. In the BN rat, the injections of... 

These differences between BN and LEW rats in susceptibility to metal-induced autoimmunity and nephropathy are associated with intrinsic differences in the immune system of these two strains. Indeed, from an immunological point of view, the balance between "type 1" (Thl/Tcl) and "type 2" (Th2/Tc2) cells is opposite in BN and LEW rats. BN rats are susceptible to "type 2"-mediated immunological disorders, to which the LEW strain is resistant. Conversely, "type l"-mediated organ-specific autoimmune disease are easily induced in LEW, but not in BN rats [155]. These immunological features depend on inherent properties of T lymphocytes. In vitro and in vivo studies have shown an inherent bias in T lymphocytes (CD4 and CDS) from BN and from LEW rats to produce respectively "type 2" (IL-4, IL-5, IL-13) and "type 1" (IFN-y cytokines [156-158]. The difference in susceptibility to metal-induced autoimmunity and nephropathy of BN and LEW strains provides a unique tool to study their genetic control. 

In addition to penicillamine nephropathy, other side effects of the drug may be related to the widespread deposition of immune complexes (Figure 3). Dense, granular immunoglobuhn deposits have been identified at the epidermodermal junction in 4 rheumatoid arthritis patients who developed toxic reactions, such as severe rashes, thrombocytopenia, aplastic anemia, and proteinuria. Three of 4 penicillamine-induced systemic lupus erythematosus syndrome patients had similar findings on skin biopsy [161]. 

PalosuoT, Provast TT, Milgrom F. Gold nephropathy. Serologic data suggesting an immune complex disease. Clin Exp Immunol 1976 25 311-318. 

Ueda S, Wakashin Y, Yoshida H, Mori T, Mori Y, Azemoto R, Ogawa M, Kato I, Wakashin M. Gold nephropathy - effect of gold on immune response to renal tubular basement membrane (TBM) antigen in mice. In Nephrotoxicity./nv/fro to in vivo, animals to man. Bach BH, Lock EA, editors. Plenum, New York 1989 p. 139-145. 

The immunological studies have failed to indicate that immune disorders participate in the pathogenesis of Balkan nephropathy, with some of detected changes having been attributed to advanced renal failure [111]. 

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