Detection of humoral and cell-mediated immunity to kidney basement membranes in human renal diseases

Abstract

The presence of antiglomerular basement membrane and antitubular basement membrane antibodies was tested by passive hemagglutination in the serum of 194 patients with renal disease and in the serum of thirty-nine control subjects. Seven per cent of the patients with renal disease had circulating antibodies to both glomerular and tubular basement membranes (titers 1:16 to 1:64); results were always negative in the control subjects. The patients with positive results had focal glomerulonephritis, diffuse proliferative glomerulonephritis or nephropathies with major vascular lesions, i.e., polyarteritis nodosa,thrombotic microangiopathy and cortical necrosis. Using immunofluorescent microscopy, linear deposits of immunoglobulin G (IgG) and complement 3 (C′3) were found in one patient with focal glomerulonephritis and in one patient with diffuse proliferative glomerulonephritis. In these two patients only, hemagglutinating antiglomerular basement membrane antibodies exhibited a high affinity for the glomerular basement membrane. Cell-mediated immunity was evaluated in eighty-three of the patients with renal disease and sixteen of'the control subjects. Fourteen patients with renal disease, 50 per cent of whom were seronegative by passive hemagglutination, exhibited a positive leukocyte migration test; results were negative in all control subjects. The patients with a positive leukocyte migration test belonged only to the same pathologic groups already given. The rosette test, performed in twenty cases, was positive in all patients with circulating antiglomerular basement membrane antibodies and negative in the others. It is suggested that both cell-mediated and humoral immunity can be the consequence of severe proliferative glomerulonephritis or nephropathies with major vascular lesions, but only the high affinity antiglomerular basement membrane antibodies, such as those found in focal glomerulonephritis with linear deposits, play a role in the pathogenesis of glomerulonephritis.