IgG4-Related Disease Is Not Associated with Antibody to the Phospholipase A2 Receptor

Patients with IgG4-related disease (IgG4-RD) share histopathological characteristics that are similar across affected organs. The finding of infiltration with IgG4+ plasma cells in the proper clinical and histopathological contexts connects a large number of clinical entities that were viewed previously as separate conditions. The renal involvement in IgG4-RD is usually characterized by tubulointerstitial nephritis, but membranous nephropathy has also been reported to be one of the renal complications of IgG4-RD. The recent discovery that a high proportion of patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies to the M-type phospholipase A2 receptor (PLA2R) in the circulation and glomerular immune deposits, together with the profound IgG4 hypergammaglobulinemia and occasional reports of membranous nephropathy in IgG4-RD, raised the question of a common antigen. To assess the presence of anti-PLA2R antibody in patients with IgG4-RD, we screened sera from 28 IgG4-RD patients by immunoblot. None of the patients in this cohort had detectable circulating anti-PLA2R antibodies. This study suggests that despite some clinical and serological overlaps between IgG4-RD and IMN,anti-PLA2R antibodies do not play a role in the pathogenesis of IgG4-RD. Additional studies of IgG4-RD with evidence of membranous nephropathy are important to exclude any definite relationship.

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PLA2R-Negative Membranous Nephropathy Presenting as a Prodrome of IgG4-Related Autoimmune Pancreatitis

Case Reports in Nephrology and Dialysis ◽

10.1159/000501260 ◽

2019 ◽

Vol 9 (2) ◽

pp. 85-91

Author(s):

Magdalini Velegraki ◽

Kostas G. Stylianou ◽

Dimitrios Xydakis ◽

Hariklia Gakiopoulou ◽

Evangelos Voudoukis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Autoimmune Pancreatitis ◽

Membranous Nephropathy ◽

Tubulointerstitial Nephritis ◽

Pathological Feature ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Phospholipase A2 Receptor ◽

History Of

Membranous nephropathy (MN) with tubulointerstitial nephritis (TIN) is an established manifestation of immunoglobulin G4 (IgG4)-related disease (IgG4-RD). A pathological feature aiming to distinguish between primary and secondary MN is the presence or absence of glomerular staining for phospholipase A2 receptor (PLA2R), respectively. Isolated MN without TIN has been rarely reported in the context of IgG4-RD. This case report describes a patient with a history of MN successfully treated with steroids and cyclophosphamide, who, 3 years later, presented with unexplained exacerbation of diabetes mellitus due to IgG4-related autoimmune pancreatitis. Pancreatitis was treated, and diabetes improved after treatment with steroids. Based on the presence of isolated IgG4 glomerular capillary deposits along with negative staining for PLA2R and the metachronous appearance of autoimmune pancreatitis, MN was retrospectively classified as secondary to IgG4-RD. Isolated IgG4-positive/PLA2R-negative MN without TIN can be a prodrome of IgG4-RD, reminiscent of MN secondary to neoplasms.

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Phospholipase A2 receptor–associated membranous nephropathy in a patient with IgG4-related disease

Medicine ◽

10.1097/md.0000000000015616 ◽

2019 ◽

Vol 98 (20) ◽

pp. e15616 ◽

Cited By ~ 1

Author(s):

Saif A. Muhsin ◽

Ricard Masia ◽

Rex N. Smith ◽

Zachary S. Wallace ◽

Cory A. Perugino ◽

...

Keyword(s):

Phospholipase A2 ◽

Membranous Nephropathy ◽

Related Disease ◽

Igg4 Related Disease ◽

Phospholipase A2 Receptor

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Renal Involvement in IgG4-Related Disease: From Sunlight to Twilight

Frontiers in Medicine ◽

10.3389/fmed.2021.635706 ◽

2021 ◽

Vol 8 ◽

Author(s):

Riccardo Capecchi ◽

Domenico Giannese ◽

Diego Moriconi ◽

Angelo G. Bonadio ◽

Federico Pratesi ◽

...

Keyword(s):

Kidney Disease ◽

Plasma Cells ◽

Retroperitoneal Fibrosis ◽

Tubulointerstitial Nephritis ◽

Renal Involvement ◽

Organ Damage ◽

Related Disease ◽

Igg4 Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Storiform Fibrosis

IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern (dense lymphoplasmacytic infiltrate with prevalent IgG4+ plasma cells and storiform fibrosis), which may involve the kidney both directly (IgG4-related kidney disease, IgG4-RKD) or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease.

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Case Review of lgG4-Related Disease Patient with Combined Tubulointerstitial Nephritis and Membranous Nephropathy Coexisting with Cholangiocarcinoma: Case Report

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.11.10685 ◽

2020 ◽

Vol 103 (11) ◽

pp. 1230-1235

Keyword(s):

Renal Failure ◽

Membranous Nephropathy ◽

Tubulointerstitial Nephritis ◽

Disease Patient ◽

Case Review ◽

Related Disease ◽

Phospholipase A2 Receptor ◽

Wide Range ◽

Serum Igg4 ◽

Secondary Membranous Nephropathy

Immunoglobulin G4-related disease (IgG4-RD) has recently been recognized as an autoimmune disorder involving multiple organs. The kidney is a represented organ with a wide range of renal manifestations. The authors report a case of an 83-year-old Thai male with combined IgG4 tubulointerstitial nephritis and membranous nephropathy coexisting with cholangiocarcinoma. The patient presented with proteinuria, acute renal failure, eosinophilia, hypocomplementemia, and high serum IgG4 concentration. The diagnosis was IgG 4-related tubulointerstitial nephritis and membranous nephropathy on renal biopsy, with negative immunohistochemistry for anti-phospholipase A2 receptor antibodies. Magnetic resonance imaging (MRI) abdomen showed two wedge shaped arterial enhancing lesions of liver. Liver biopsy revealed adenocarcinoma, compatible with cholangiocarcinoma. Proteinuria and renal failure were resolved with initial steroid treatment. Meanwhile, IgG4-related membranous nephropathy should be considered in the differential diagnosis for patients with proteinuria. Potentially, IgG4-RD may be rarely associated with carcinoma development. However, further studies are recommended to ratify and confirm the association between IgG4-RD and incidence of malignancies. Keywords: IgG4-related disease, Membranous nephropathy, Secondary membranous nephropathy, Tubulointerstitial nephritis, Cholangiocarcinoma

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Tubulointerstitial Nephritis and Other Renal Involvement by IgG4-Related Disease

Autoimmune (IgG4-related) Pancreatitis and Cholangitis ◽

10.1007/978-1-4419-6430-4_18 ◽

2013 ◽

pp. 189-197

Author(s):

Lynn D. Cornell ◽

Naoki Takahashi

Keyword(s):

Tubulointerstitial Nephritis ◽

Renal Involvement ◽

Related Disease ◽

Igg4 Related Disease

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Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement

Immunologic Research ◽

10.1007/s12026-020-09163-3 ◽

2020 ◽

Vol 68 (6) ◽

pp. 340-352

Author(s):

Giacomo Quattrocchio ◽

Antonella Barreca ◽

Andrea Demarchi ◽

Roberta Fenoglio ◽

Michela Ferro ◽

...

Keyword(s):

B Cells ◽

B Lymphocyte ◽

Plasma Cells ◽

Renal Involvement ◽

Elevated Serum ◽

Long Term Effects ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Storiform Fibrosis

AbstractIgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

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IgG4-Related Tubulointerstitial Nephritis Associated with Membranous Nephropathy in Two Patients: Remission after Administering a Combination of Steroid and Mizoribine

Case Reports in Nephrology ◽

10.1155/2014/678538 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Kana N. Miyata ◽

Hiromi Kihira ◽

Manabu Haneda ◽

Yasuhide Nishio

Keyword(s):

Renal Biopsy ◽

Membranous Nephropathy ◽

Plasma Cells ◽

Tubulointerstitial Nephritis ◽

High Serum ◽

Immunoglobulin G4 ◽

Japanese Men ◽

Renal Lesions ◽

Igg4 Related Disease ◽

Prednisolone Treatment

We report two cases of Japanese men who presented with proteinuria, eosinophilia, hypocomplementemia, and high serum immunoglobulin G4 (IgG4) concentration and were diagnosed with membranous nephropathy associated with IgG4-related tubulointerstitial nephritis on renal biopsy. The typical renal lesions of IgG4-related disease are tubulointerstitial nephritis, which improves remarkably with steroid therapy, and occasional glomerular changes. In our two cases, renal biopsy revealed IgG4-positive immune complex deposits in glomeruli in a pattern of membranous nephropathy and concurrent tubulointerstitial nephritis with IgG4 plasma cells. In both cases, proteinuria persisted with initial prednisolone treatment and was resolved only after the addition of mizoribine. We report the first two cases in which the combination of prednisolone and mizoribine was effective for treating membranous nephropathy associated with IgG4-related tubulointerstitial nephritis.

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