Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy

Oda, Hiroshi; Wakui, Hideki; Komatsuda, Atsushi; Okuyama, Shin; Masai, Rie; Maki, Nobuki; Kigawa, Akihiro; Sawada, Kenichi; Imai, Hirokazu

doi:10.1093/ndt/gfg616

Cited by 180 publications

(121 citation statements)

References 17 publications

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“…To further investigate the pathogenesis of mercury-induced MN, the glomerular IgG subclass was observed. The deposits of both IgG1 and IgG4 (predominantly IgG1) were observed for mercury-induced MN, which differed from the feature of deposits of IgG4 in idiopathic MN (13) but was similar to the secondary MN due to malignancy (14). The distribution of IgG subclass varies because of the Th1 and Th2 predominant immune responses: IgG1 and IgG3 are involved in the Th1-type predominant immune response, whereas IgG4 is more active in the Th2-type predominant immune response (15).…”

Section: Discussionmentioning

confidence: 72%

Mercury-Induced Membranous Nephropathy

Zhang

Chen

et al. 2010

Clinical Journal of the American Society of Nephrology

116

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Results: A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q. IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached complete remission in follow-up after withdrawal from mercury exposure.Conclusions: Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible cause of membranous nephropathy.

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Section: Discussionmentioning

confidence: 72%

Mercury-Induced Membranous Nephropathy

Zhang

Chen

et al. 2010

Clinical Journal of the American Society of Nephrology

116

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“…IgG4-predominant staining is associated with primary membranous glomerulopathy, whereas IgG1, IgG2, and IgG3 predominate in the deposits of secondary membranous glomerulopathy. 3,[23][24][25][26] However, the sensitivity and specificity of various IgG subtype staining patterns for primary membranous glomerulopathy has not been well documented. We examined the IgG subtypes in cases of secondary membranous with positive PLA2R1 to determine whether they would follow the pattern of idiopathic membranous glomerulopathy with IgG4-predominant staining or that of secondary membranous glomerulopathy with IgG1 À 3 dominant staining.…”

Section: Discussionmentioning

confidence: 99%

Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies

et al. 2013

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Autoantibody formation directed against phospholipase A2 receptor (PLA2R)1 is the underlying etiology in most cases of primary membranous glomerulopathy. This new understanding of the pathogenesis of primary membranous is in the process of transforming the way the disease is diagnosed. We validated an indirect immunofluorescence assay to examine PLA2R1 in renal biopsies utilizing a commercially available antibody and standard indirect immunofluorescence. Using this assay, we examined a total of 165 cases of membranous glomerulopathy including 85 primary and 80 secondary. We found tissue staining for PLA2R1 to have a sensitivity of 75% (95% CI 65 À 84%) and a specificity of 83% (95% CI 72 À 90%) for primary membranous glomerulopathy. Hepatitis C virus was the secondary etiology with the most number of cases staining positive for PLA2R1 (7/11, 64%) followed by sarcoidosis (3/4, 75%) and neoplasm (3/12, 25%). Autoimmune etiologies showed rare PLA2R1-positive staining (1/46, 2%). All cases of secondary membranous glomerulopathy with positive PLA2R1 showed IgG4-predominant staining, which is typically associated with primary membranous glomerulopathy. This IgG4 predominance raises the possibility that these cases are more pathogenically related to primary membranous glomerulopathy than secondary. We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy utilizing a technique that is readily adoptable by most renal pathology laboratories.

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“…In contrast, several papers indicate that in secondary forms of membranous glomerulonephritis, the IgG subclass distribution is different from the primary form, and the deposits are frequently not IgG4 dominant. [9][10][11][12][13][14][15][16] However, even idiopathic membranous glomerulonephritis is a heterogeneous disease if we consider the morphological appearance of the glomeruli during disease progression. Membranous glomerulonephritis, by pathological criteria, is divided into four stages according to Ehrenreich and Churg.…”

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confidence: 99%

IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression

et al. 2013

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Recent breakthrough findings revealed that most patients with idiopathic (primary) membranous glomerulonephritis have IgG4 antibodies to the phospholipase A2 receptor (PLA2R). These IgG4 antibodies can be detected in the glomerular immune complexes and they colocalize with PLA2R. In secondary forms of membranous glomerulonephritis, such IgG4 antibodies are absent or less prevalent. There are no studies addressing the IgG subclass distribution across different stages of membranous glomerulonephritis. During a 25-month period, we identified 157 consecutive biopsies with membranous glomerulonephritis with adequate tissue for light, immunofluorescence and electron microscopy. Of the 157 membranous glomerulonephritis cases, 114 were primary membranous glomerulonephritis and 43 were secondary membranous glomerulonephritis. We compared the intensity of IgG subclass staining (on a semiquantitative scale of 0 to 3 þ ) and the IgG subclass dominance between primary and secondary membranous glomerulonephritis and between the different stages of membranous glomerulonephritis. In primary membranous glomerulonephritis most (76% of cases) were IgG4 dominant. In contrast, in secondary membranous glomerulonephritis IgG1 was dominant in 60% of biopsies (P ¼ 0.0018). Interestingly, in early stage (stage 1) primary membranous glomerulonephritis, IgG1 was the dominant IgG subclass (64% of cases); in all later stages IgG4 dominated (P ¼ 0.0493). It appears that there is an inverse relationship between the intensity of glomerular capillary IgG4 and C1q staining. In secondary forms of membranous glomerulonephritis (heterogeneous group with low case numbers), we did not find such associations. Our data indicate that in early stage membranous glomerulonephritis, antibody response is different from later stages, with IgG1 dominant deposits. It is possible that early on, antigens other than PLA2R have an important role, Alternately, there may be an IgG subclass switch in the antibody response with IgG4 taking over later as the dominant immunoglobulin.

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Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy

Abstract: Our findings suggest that the distribution patterns of glomerular IgG subclass deposits are different in idiopathic MN and M-MN. The strong IF intensity of glomerular IgG1 and IgG2 in M-MN may provide a possible predictor for this condition.

Cited by 180 publications

References 17 publications

Mercury-Induced Membranous Nephropathy

Mercury-Induced Membranous Nephropathy

Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies

IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression

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