Specificity and cross‐reactive idiotypes of anti‐glomerular basement membrane autoantibodies in HgCl₂‐induced autoimmune glomerulonephritis

Abstract

Mercury-induced autoimmune glomerulonephritis in the Brown-Norway (BN) rat is characterized by the successive appearance of linear and granular glomerular IgG deposits. Anti-laminin autoantibodies represent the major part of the anti-glomerular basement membrane (GBM) antibodies produced in this model. Fusions were performed in this model and four anti-GBM monoclonal antibodies (mAb) were obtained. Three of them were laminin specific. Using rabbit anti-idiotype antibodies, cross-reactive idiotypes (CRId) were characterized on anti-laminin antibodies. They were expressed on the three anti-laminin mAb, on kidney-eluted and circulating anti-laminin antibodies. CRId-bearing immunoglobulins were detected transiently in the circulation and paralleled the anti-laminin antibody activity. By immunofluorescence studies on kidney cryostat sections two different CRId were defined. One was localized close to the antigen-combining site since it was not revealed on kidney-bound antibodies, in contrast with the second CRId. This latter CRId was also found deposited in a typical linear pattern in the early phase of the disease and in a granular pattern in the late phase, demonstrating that these CRId are components of immune deposits. Taken together, these results suggest that in this model of T-dependent polyclonal B cell activation, restricted sets of V genes encode for at least a part of the anti-GBM autoantibodies.

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

“…Addison's disease 17 alpha Hydroxylase [117] 21 Hydroxylase [118] Central nervous system Multiple sclerosis Myelin-associated protein [119] Neurofilament triplet M protein [120] Cerebellum Paraneoplastic cerebellar degeneration Cerebellar degeneration associated protein [121] Heart Coxsackie myocarditis Cardiac myosin heavy chain [122] Kidney Basement membrane disease Laminin beta 2 chain [123] Glomerulonephritis Myeloperoxidase [124] Liver Chronic active hepatitis Cytochrome P450 [125] Primary biliary cirrhosis Pyruvate dehydrogenase [126] NADH dehydroreductase [127] Dihydrolipoamide dehydrogenase [128] Lung and kidney Goodpasture's syndrome Laminin beta 2 chain [123] Neuromuscular junction Myasthenia gravis Acetylcholine receptor [129] Pancreas Diabetes insulin dependent Glutamic acid decarboxylase [130] Skin Pemphigoid Bullous pemphigoid antigen [131] Scleroderma KU autoimmune antigen [132] Synovial joints Rheumatoid arthritis Cytokeratin [118,133] Thyroid Hashimoto's thyroiditis Thyroglobulin [134] Various Systems Systemic lupus erythematosus DNA-binding protein [135] Hsp90 [136] Adapted from [2].…”

Resistance to Xenobiotic-Induced Autoimmunity Maps to Chromosome 1

“…Exposure to large doses results in acute renal tubular lesions and immunosuppression, whereas chronic administration of smaller doses can lead to the development of systemic autoimmunity (2)(3)(4). The characteristic features of mercury-induced autoimmunity (HgIA) 3 are very similar to many of the manifestations of systemic lupus erythematosus, and include lymphocyte proliferation (5), increased levels of class II MHC expression (6,7), hypergammaglobulinemia (8,9), polyclonal Abs to self Ags, including anti-nuclear Abs (8,10), immune complex glomerulonephritis (GN) (10), and necrotizing vasculitis (11). HgIA is also similar to lupus in that the disease process requires CD4 ϩ T cells (12,13), certain B and T cell costimulatory molecules (14), and IFN-␥ (15), which strongly supports the possibility of related or identical pathogenic mechanisms.…”

Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.

“…The ratio of RT6-to RT6+ cells did not usually vary in experimental animals versus controls, except for a modest increase (37%, p = 0.0186) observed in lymph node cells only on day 23. As shown in Figure 2, which compares values obtained from animals of different strains, there was no significant change in the RT6 ratio of LEW rats sacrificed on day 16.…”

“…Values for the spleen were more constant, with the only significant percentage changes noted on day 30, when there was a decrease of B-and Ia' cells. On the other hand, total cell numbers of almost all subsets were higher on days 12,16, and 23 of treatment, proportional to the moderate increase in total cell numbers. Data for experimental BN rats were obtained only on day 16, i.e., at a time when their autoimmune responses to renal antigens are at their peak (17).…”

“…On the other hand, total cell numbers of almost all subsets were higher on days 12,16, and 23 of treatment, proportional to the moderate increase in total cell numbers. Data for experimental BN rats were obtained only on day 16, i.e., at a time when their autoimmune responses to renal antigens are at their peak (17). B-cell percentages and numbers were both higher than in controls, whereas T-cell percentages de-creased and numbers increased.…”