Shane A Bobart1, Shahrzad Tehranian2, Sanjeev Sethi3, Mariam P Alexander3, Samih H Nasr3, Casal Moura Marta4, Julie A Vrana3, Samar Said3, Callen D Giesen3, John C Lieske2, Fernando C Fervenza2, An S De Vriese5. 1. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Cleveland Clinic Florida, Weston. 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. 4. Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN. 5. Division of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge, Brugge, Belgium; Ghent University, Ghent, Belgium. Electronic address: an.devriese@azsintjan.be.
Abstract
OBJECTIVE: To describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase-A2-receptor (PLA2R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens. METHODS: A retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA2R-, THSD7A-, SEMA3B-, NELL-1-, PCDH7-, EXT1/EXT2-, NCAM-1-associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis. RESULTS: Patients with PLA2R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA2R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1-, PCDH7-, and NCAM-1-associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity. CONCLUSION: The widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.
OBJECTIVE: To describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase-A2-receptor (PLA2R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens. METHODS: A retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA2R-, THSD7A-, SEMA3B-, NELL-1-, PCDH7-, EXT1/EXT2-, NCAM-1-associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis. RESULTS:Patients with PLA2R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA2R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1-, PCDH7-, and NCAM-1-associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity. CONCLUSION: The widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.
Authors: Shane A Bobart; Heedeok Han; Shahrzad Tehranian; An S De Vriese; Juan Carlos Leon Roman; Sanjeev Sethi; Ladan Zand; Cristina Andrades Gomez; Callen D Giesen; Maria Jose Soler; Andrew S Bomback; Fernando C Fervenza Journal: Clin J Am Soc Nephrol Date: 2021-11-15 Impact factor: 8.237
Authors: Janina Müller-Deile; Nina Sopel; Alexandra Ohs; Victoria Rose; Marwin Gröner; Christoph Wrede; Jan Hegermann; Christoph Daniel; Kerstin Amann; Gunther Zahner; Mario Schiffer Journal: J Am Soc Nephrol Date: 2021-11 Impact factor: 10.121
Authors: Sanjeev Sethi; Benjamin Madden; Hanna Debiec; Johann Morelle; M Cristine Charlesworth; LouAnn Gross; Vivian Negron; David Buob; Sidharth Chaudhry; Michel Jadoul; Fernando C Fervenza; Pierre Ronco Journal: J Am Soc Nephrol Date: 2021-04-08 Impact factor: 10.121
Authors: Sanjeev Sethi; Benjamin Madden; Marta Casal Moura; Samih H Nasr; Nattawat Klomjit; LouAnn Gross; Vivian Negron; M Cristine Charlesworth; Mariam P Alexander; Nelson Leung; Ulrich Specks; Fernando C Fervenza; Mark Haas Journal: J Am Soc Nephrol Date: 2022-03-23 Impact factor: 14.978