Anti-contactin 1 Antibody-associated Membranous Nephropathy in Chronic Inflammatory Demyelinating Polyneuropathy with Several Autoantibodies.

A 50-year-old man diagnosed with anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was referred to our department for the evaluation of proteinuria. A kidney biopsy revealed membranous nephropathy (MN). Immunohistochemistry for CNTN1 revealed positive granular staining along the glomerular basement membrane, confirming anti-CNTN1 antibody-associated MN. Immunofluorescence showed a full-house pattern, and several autoantibodies, such as anti-nuclear antibody, anti-double-strand DNA antibody, and anti-cardiolipin antibody, were detected in the patient's serum. Although limited autoantibodies have been investigated in some of the reported cases, a variety of autoantibodies might be produced in anti-CNTN1 antibody-associated CIDP, accompanied by MN.

A Case of M-Type Phospholipase A2 Receptor-Associated Membranous Nephropathy With IgG4-Positive Cells Infiltration in the Interstitium.

A 70-year-old man was referred to our department for evaluation of nephrotic syndrome. Renal biopsy revealed membranous nephropathy (MN). Immunohistochemical analysis demonstrated IgG4-positive staining in the glomeruli and interstitial cells. The presence of serum anti-phospholipase A2 receptor (PLA2R) antibody and enhanced staining of PLA2R in the glomeruli was noted. Computed tomography unidentified the extrarenal lesions of IgG4-related disease. He was diagnosed with PLA2R-associated MN possibly complicated with IgG4 related kidney disease (IgG4-RKD). Storiform fibrosis, a typical manifestation of IgG4-RKD, was not apparent. We herein describe a case of serologically and histologically confirmed PLA2R-associated MN with IgG4+ cell infiltration into the interstitium without any signs of IgG4-RD.

Prevalence of neural epidermal growth factor-like 1- and exostosin 1/exostosin 2-associated membranous nephropathy: a single-center retrospective study in Japan.

Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. We previously reported that the prevalence of phospholipase A2 receptor (PLA2R)- and thrombospondin type 1 domain containing 7A (THSD7A)-associated MN patients in Japan is 52.7% and 9.1%, respectively. In addition to PLA2R and THSD7A, we assessed the presence of newly discovered target antigens, neural epidermal growth factor-like 1 (NELL-1), semaphorin 3B (SEMA3B), and exostosin 1/exostosin 2 (Ext1/Ext2), in renal specimens from patients with primary and secondary MN by immunohistochemistry. We found enhanced glomerular staining of PLA2R, THSD7A, NELL-1, and Ext1/Ext2 in 53.6%, 8.7%, 1.5%, and 13.0% of the renal samples, respectively, in patients with primary MN. None of the patient specimens showed enhanced staining of SEMA3B. Enhanced glomerular staining of PLA2R, NELL-1, and Ext1/Ext2 was detected in 5.7%, 8.6%, and 22.9% of the patients with secondary MN, respectively. Based on our findings, we recommend the assessment of PLA2R, THSD7A and NELL-1 in addition to clinical information and IgG4 staining to differentiate between primary and secondary MN. This would aid in distinguishing secondary MN patients from primary MN patients who coincidentally have some secondary characteristics.

Primary Membranous Nephropathy With Enhanced Staining of Exostosin 1/Exostosin 2 in the Glomeruli: A Report of 2 Cases.

Technological advances have allowed the discovery of 6 subtypes of membranous nephropathy based on target antigens: M-type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), neural epidermal growth factor-like 1 protein, semaphorin 3B, exostosin 1 (EXT1), and EXT2. EXT1/EXT2 are thought to be associated with secondary (autoimmune) membranous nephropathy. Although it has been reported that PLA2R- and THSD7A-associated membranous nephropathy have rarely been detected concomitantly, there have been no previous reports demonstrating PLA2R- or THSD7A-associated membranous nephropathy with enhanced glomerular staining of EXT1/EXT2. We describe 2 cases of primary membranous nephropathy with enhanced glomerular staining of EXT1/EXT2. Patient 1 was diagnosed with PLA2R-associated primary membranous nephropathy, and patient 2 was diagnosed with THSD7A-associated primary membranous nephropathy. Both patients achieved clinical remission in response to immunosuppressive therapy. Neither patient demonstrated signs of autoimmune diseases, and antinuclear antibodies were absent in their sera. Based on these 2 cases, enhanced staining of EXT1/EXT2 in glomeruli, although rare, can be detected in primary membranous nephropathy without autoimmune diseases.