Diverse Clinical Presentations of C3 Dominant Glomerulonephritis
C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of “typical” C3 glomerulopathy (C3G). In both iMPGN and C3G, a f...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2020.00293/full |
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| author | Ramy M. Hanna Ramy M. Hanna Jean Hou Huma Hasnain Farid Arman Umut Selamet Umut Selamet James Wilson Samuel Olanrewaju Jonathan E. Zuckerman Marina Barsoum Julie M. Yabu Ira Kurtz Ira Kurtz |
| author_facet | Ramy M. Hanna Ramy M. Hanna Jean Hou Huma Hasnain Farid Arman Umut Selamet Umut Selamet James Wilson Samuel Olanrewaju Jonathan E. Zuckerman Marina Barsoum Julie M. Yabu Ira Kurtz Ira Kurtz |
| author_sort | Ramy M. Hanna |
| collection | DOAJ |
| description | C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of “typical” C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage. Dysregulation of the alternative complement pathway and mutations in certain regulatory factors are highly implicated in C3 glomerulopathy (which encompasses C3 glomerulonephritis, dense deposit disease, and cases of C3 dominant MPGN). We report three cases that demonstrate that an initial biopsy diagnosis of iMPGN does not exclude complement alterations similar to the ones observed in patients with a diagnosis of C3G. The first patient is a 39-year-old woman with iMPGN and C3 dominant staining, with persistently low C3 levels throughout her course. The second case is a 22-year-old woman with elevated anti-factor H antibodies and C3 dominant iMPGN findings on biopsy. The third case is a 25-year-old woman with C3 dominant iMPGN, dense deposit disease, and a crescentic glomerulonephritis on biopsy. We present the varied phenotypic variations of C3 dominant MPGN and review clinical course, complement profiles, genetic testing, treatment course, and peri-transplantation plans. Testing for complement involvement in iMPGN is important given emerging treatment options and transplant planning. |
| first_indexed | 2024-12-14T17:47:12Z |
| format | Article |
| id | doaj.art-f0068d104fdc41bb97ddf27fc7e68809 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-14T17:47:12Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-f0068d104fdc41bb97ddf27fc7e688092022-12-21T22:52:44ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-06-01710.3389/fmed.2020.00293520865Diverse Clinical Presentations of C3 Dominant GlomerulonephritisRamy M. Hanna0Ramy M. Hanna1Jean Hou2Huma Hasnain3Farid Arman4Umut Selamet5Umut Selamet6James Wilson7Samuel Olanrewaju8Jonathan E. Zuckerman9Marina Barsoum10Julie M. Yabu11Ira Kurtz12Ira Kurtz13Division of Nephrology, Department of Medicine, UCI School of Medicine, Irvine, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDavid Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesDepartment of Medicine, Division of Nephrology, David Geffen UCLA School of Medicine, Los Angeles, CA, United StatesUCLA Brain Research Institute, Los Angeles, CA, United StatesC3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of “typical” C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage. Dysregulation of the alternative complement pathway and mutations in certain regulatory factors are highly implicated in C3 glomerulopathy (which encompasses C3 glomerulonephritis, dense deposit disease, and cases of C3 dominant MPGN). We report three cases that demonstrate that an initial biopsy diagnosis of iMPGN does not exclude complement alterations similar to the ones observed in patients with a diagnosis of C3G. The first patient is a 39-year-old woman with iMPGN and C3 dominant staining, with persistently low C3 levels throughout her course. The second case is a 22-year-old woman with elevated anti-factor H antibodies and C3 dominant iMPGN findings on biopsy. The third case is a 25-year-old woman with C3 dominant iMPGN, dense deposit disease, and a crescentic glomerulonephritis on biopsy. We present the varied phenotypic variations of C3 dominant MPGN and review clinical course, complement profiles, genetic testing, treatment course, and peri-transplantation plans. Testing for complement involvement in iMPGN is important given emerging treatment options and transplant planning.https://www.frontiersin.org/article/10.3389/fmed.2020.00293/fullcomplement mutationsmembranoproliferative glomerulonephritisalternative pathwayC3 glomerulonephritisproteinuria |
| spellingShingle | Ramy M. Hanna Ramy M. Hanna Jean Hou Huma Hasnain Farid Arman Umut Selamet Umut Selamet James Wilson Samuel Olanrewaju Jonathan E. Zuckerman Marina Barsoum Julie M. Yabu Ira Kurtz Ira Kurtz Diverse Clinical Presentations of C3 Dominant Glomerulonephritis Frontiers in Medicine complement mutations membranoproliferative glomerulonephritis alternative pathway C3 glomerulonephritis proteinuria |
| title | Diverse Clinical Presentations of C3 Dominant Glomerulonephritis |
| title_full | Diverse Clinical Presentations of C3 Dominant Glomerulonephritis |
| title_fullStr | Diverse Clinical Presentations of C3 Dominant Glomerulonephritis |
| title_full_unstemmed | Diverse Clinical Presentations of C3 Dominant Glomerulonephritis |
| title_short | Diverse Clinical Presentations of C3 Dominant Glomerulonephritis |
| title_sort | diverse clinical presentations of c3 dominant glomerulonephritis |
| topic | complement mutations membranoproliferative glomerulonephritis alternative pathway C3 glomerulonephritis proteinuria |
| url | https://www.frontiersin.org/article/10.3389/fmed.2020.00293/full |
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