IGG SUBCLASS DEPOSITS IN GLOMERULI OF LUPUS AND NONLUPUS MEMBRANOUS NEPHROPATHIES

Membranous nephropathy (MN) accounts for approximately 10% of all renal lesions of systemic lupus erythematosus (SLE). These membranous lesions often have a clinical presentation similar to that of idiopathic MN and may present before SLE is apparent clinically. However, unlike proliferative lesions of lupus nephritis (LN), membranous LN often does not show a “full-house” pattern of glomerular immunoglobulin and complement (C) deposits by immunofluorescence (IF); only nine of 14 such lesions that we examined stained for all of the following: IgG, IgA, IgM, C3, and C1q. Iskandar et al reported in 1992 that most cases of diffuse proliferative LN showed IgG3 as the major IgG subclass present in glomerular deposits; by contrast, IgG4 predominated in six of seven cases of MN of unspecified etiology. If IgG subclass deposition is similar in membranous and proliferative lesions of LN, then IF staining for IgG3 and IgG4 may be helpful in distinguishing lupus from nonlupus lesions in patients with MN who are lacking a firm diagnosis of SLE. We therefore stained cryostat sections of renal biopsies from 14 patients with SLE and MN (without a proliferative component; World Health Organization [WHO] classes Va and Vb) and 28 non-SLE patients with MN for IgG subclasses by direct IF; the observer was blind to the diagnosis for each case until all were read. The intensity of glomerular staining was graded on a 0 to 4+ scale with increments of 0.5+. In seven of 14 cases of lupus MN, IgG3 staining intensity exceeded that of IgG4 by at least 1.0+ (IgG3>IgG4); in the remaining seven cases, IgG3 and IgG4 staining intensity did not differ by more than 0.5+ (IgG3 ≅ IgG4). In no case of lupus MN did IgG4 staining intensity exceed that of IgG3 by 1.0+ or more (IgG3 < IgG4). By contrast, 22 of 28 cases of nonlupus MN showed IgG3 < IgG4, with the remaining six showing IgG3 ≅ IgG4. In four SLE cases (but no non-SLE cases), staining for IgG3 but no other IgG subclass was noted prominently in the mesangium. Glomerular IgA and C1q deposition was also more prevalent in lupus MN than in nonlupus MN. The results suggest that IgG subclass staining may be useful in helping distinguish nonlupus from lupus MN in some cases where the diagnosis of SLE is equivocal, and may also help identify mesangial immune complex deposits in some cases of lupus MN. © 1994, National Kidney Foundation. All rights reserved. All rights reserved.