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Fig 2. Early segmental fibrinoid necrosis with early cellular crescent formation without endocapillary proliferation or evidence of immune complexes in the remaining glomerular tuft. This light microscopic finding is that of a pauci-immune necrotizing glomerulonephritis, with a specific diagnosis of anti-GBM antibody-mediated glomerulonephritis made by immunofluorescence (see Fig 3) (Jones silver stain; original magnification 3400).

The influence of HLA-linked genes on anti-GBM antibody-mediated nephritis. Thirty-nine Caucasian patients with glomerulonephritis caused by autoantibodies to glomerular basement membrane (GBM) were studied. They were segregated into three groups depending on presentation: Group 1 (19 patients) were anuric or oliguric, group 2 (13 patients) had rapidly deteriorating renal function but were not oliguric, and group 3 (seven patients) had stable renal function. The incidence of HLA-DR2 was greatly increased; it was present in 34 of 38 patients in whom DR antigens were identified compared to 43 of 154 controls (Pc = 0.63 × 10 -8 , relative risk 36, etiological fraction 0.86). The incidence of HLA-B7 was also increased; present in 23 of 39 patients and 43 of 193 controls (Pc = 0.26 × 10 -4 , relative risk 5.0, etiological fraction 0.43). These data were analyzed for a third order association between HLA-DR2, HLA-B7, and anti-GBM disease. Such an association was probable for patients in group 1 (P = 0.27 × 10 -6 ), likely for those in group 2 (P = 0.024) but unlikely for patients in group 3 (P = 0.62) suggesting HLA-B7-associated genes influence severity. Clinical results from a subset of the patients referred directly on presentation showed that patients who inherited HLA-B7 together with DR2 had significantly higher plasma creatinines, a greater proportion of glomeruli surrounded by crescents and a worse prognosis. Despite this there was little difference in severity of their lung disease. Influence des genes lies a HLA sur la severite de la nephrite mediee par un anticorps anti-GMB. Trente-neuf malades blancs atteints de glomerulonephrite due a des anticorps diriges contre la membrane basale glomerulaire (GBM) ont ete etudies. Ils ont ete divises en trois groupes en fonction du tableau: ceux du groupe 1 (19 malades) etaient anuriques ou oliguriques, ceux du groupe 2 (13 malades) avaient une fonction renale se deteriorant rapidement mais n'etaient pas oliguriques, et ceux du groupe 3 (sept malades) avaient une fonction renale stable. L'incidence de HLA-DR2 etait tres augmentee; il etait present chez 34 des 38 malades chez qui les antigenes DR avaient ete identifies, par rapport a 43 de 154 controles (Pc = 0,63 × 10 -8 , risque relatif 36, fraction etiologique 0,86). L'incidence de HLA-B7 etait egalement augmentee; il etait present chez 23 des 39 malades et 43 de 193 controles (Pc = 0,26 × 10 -4 , risque relatif 5,0, fraction etiologique 0,43). Ces donnees ont ete analysees pour une association du troisieme ordre entre HLA-DR2, HLA-B7, et la maladie anti-GBM. Une telle association etait probable pour les malades du groupe 1 (P = 0,27 × 10 -6 ), possible pour ceux du groupe 2 (P = 0,024), mais improbable pour ceux du groupe 3 (P = 0,62), suggerant que les genes associes a HLA-B7 influencent la severite. Les resultats cliniques d'un sous-groupe de malades adresses directement au debut ont montre que ceux qui avaient herite de HLA-B7 et de DR2 avaient des creatininemies significativement plus elvees, une plus grande proportion de glomerules entoures de croissants et un pronostic plus mauvais. Malgre cela, il y avait peu de difference de severite de leur maladie pulmonaire.