Tubular Lesions Produced by Autoantibodies to Tubular Basement Membrane in Human Renal Allografts

Abstract

In two patients with chronic glomerulonephritis who received renal allografts, transplant failure was associated with binding of transplantation antibodies to the graft and with glomerular and vascular changes frequently seen in chronic rejection. Lesions of renal tubules were characterized by basement membrane thickening, splitting or disruption, with adjacent extensive mononuclear cell infiltrates. Direct immunofluorescence showed linear staining pattern for IgG, IgA and C3 along the tubular basement membranes of the two allografts and linear staining for IgG in the tubular basement membranes of the own kidneys of one patient who had not been nephrectomized prior to renal transplantation. Indirect immunofluorescence and passive transfer studies demonstrated that theimmunoglobulins eluted from the grafts reacted with the tubular basement membranes of all human and monkey kidneys tested. Since antibodies with similar reactivity would also be eluted from the recipient’s own kidneys, they can be classified as autoantibodies. The presented data, however, do not indicate whether the autoimmune response was induced by the graft or whether the lesion just recurred in the graft.

Specificities of Antibodies Eluted from Human Cadaveric Renal Allografts

“…Additionally, the eluates contained a variety of structurally-specific antibodies. Although TBM antibodies have been reported before in renal allografts recipients (20,22,34), in the present series 22% of the eluates with antitissue antibodies contained TBM antibodies alone or in association with other structural specificities -a surprising frequency. Antibodies with apparent specificity for smooth muscle were detected in seven eluates, although no vascular Ig was detected by direct IF examination of the same kidneys.…”

“…All eluates tested had cytotoxic reactivity toward one or more cell populations. In general, those eluates (eluates 4,5,12,14,20,27) that contained antibodies reactive with T cells also were cytotoxic to B cells, but seldom with a predominantly monocyte-enriched cell population (Table IV), K and tended to be more reactive. In contrast, those eluates essentially unreactive with T cells tended to be as reactive with monocytes as with B cell preparations.…”

“…Nevertheless, results have not been consistently positive for evidence of antibodies bound to grafts, and no studies of specificities of these eluates toward intrarenal structures have been reported. Antiglomerular basement membrane (GBM)1 anti-bodies have been eluted from allografts placed into patients with circulating GBM antibodies (19) (20)(21)(22). The frequency of anti-TBM antibodies has not been studied, and there has been no systematic investigation searching for other structurally-specific antibodies in a group of rejecting (rejected) renal allografts.…”

Passive transfer of autoimmune disease with isologous IgG1 and IgG2 antibodies to the tubular basement membrane in strain XIII guinea pigs: loss of self-tolerance induced by autoantibodies.

“…In such cases it is postulated that the autoantibodies are formed as the result of basement membrane damage that results in the exposure or release of basement membrane antigens or by the formation of neoantigens through the binding of a haptenic group, such as the penicilloyl group to the basement membrane. Other examples of anti-TBM formation in man have followed renal damage of various types (2) such as immune complex glomerulonephritis (26), allograft rejection (27). Toxic damage with mercuric chloride in rats also results in anti-TBM antibody production (28).…”

Isolation of the target antigen of human anti-tubular basement membrane antibody-associated interstitial nephritis.

“…This current study provides new immunologic information on human interstitial nephritis associated with aTBM-Ab. Such an entity has been described in association with drugs (9), after renal transplantion (10), and in idiopathic form (11). The target antigen of the human autoimmune response has not been formally identified and the relationship of this human response to the model ofexperimental aTBM disease is not entirely clear.…”