Cryofibrinogen-associated glomerulonephritis with paraproteinemia
IntroductionCryofibrinogen-associated glomerulonephritis (CF-GN) is a rare disease that lacks comprehensive research and requires further investigation to improve our understanding of its pathophysiology.MethodsBased on the morphological findings from a kidney biopsy and blood tests, an elderly pati...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576917/full |
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| author | Xuanli Tang Mengya Jiang Huaqin Zhang Peng Bi Jun Wang Tian Ye Jie Zheng Mengli Tong Xingyu Zhu Xiaotao Hou Shuhua Bao Yi Lin Xue Jiang Hongyu Chen Feng Wan Haichun Yang |
| author_facet | Xuanli Tang Mengya Jiang Huaqin Zhang Peng Bi Jun Wang Tian Ye Jie Zheng Mengli Tong Xingyu Zhu Xiaotao Hou Shuhua Bao Yi Lin Xue Jiang Hongyu Chen Feng Wan Haichun Yang |
| author_sort | Xuanli Tang |
| collection | DOAJ |
| description | IntroductionCryofibrinogen-associated glomerulonephritis (CF-GN) is a rare disease that lacks comprehensive research and requires further investigation to improve our understanding of its pathophysiology.MethodsBased on the morphological findings from a kidney biopsy and blood tests, an elderly patient was diagnosed with CF-GN. Biological materials obtained from peripheral blood were utilized to treat cultured mesangial cells and mice.ResultsThe patient presented with nephrotic syndrome and chronic kidney failure. The biopsy revealed a membranoproliferative glomerulonephritis pattern with distinct substructures and positive fibrinogen staining. Cryofibrinogen was detectable under cold conditions, and monoclonal immunoglobulin (MIg) was exclusively identified within cryoprecipitates. Genetic analysis uncovered an intronic mutation. The patient partially responded to immunosuppressive therapy, but later relapsed with paraproteinemia, and the MIg was detected to have cryoactivity. To investigate the pathophysiology of CF-GN further, its cryoactivity was detected when mixing the serum (with or without MIg) with healthy control plasma. When exposed to the patient’s cryoprecipitates, cultured mesangial cells showed significant proliferation, phagocytosis of fibrinogen, and lysosomal degeneration. Injection of these cryoprecipitates into mice induced proliferative glomerulonephritis and other organ damage.ConclusionThis study provides valuable insights into the diagnosis, treatment, and pathophysiology of CF-GN with paraproteinemia. The identification of the complex of cryofibrinogen and MIg as a potential mechanism of glomerular damage shed light on the pathogenesis of this rare disease. |
| format | Article |
| id | doaj-art-99f5fed7d92746bdac9b9e135a61347d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-99f5fed7d92746bdac9b9e135a61347d2025-08-20T02:39:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15769171576917Cryofibrinogen-associated glomerulonephritis with paraproteinemiaXuanli Tang0Mengya Jiang1Huaqin Zhang2Peng Bi3Jun Wang4Tian Ye5Jie Zheng6Mengli Tong7Xingyu Zhu8Xiaotao Hou9Shuhua Bao10Yi Lin11Xue Jiang12Hongyu Chen13Feng Wan14Haichun Yang15Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Renal Pathology, King Medical Diagnostics Center, Guangzhou, ChinaDepartment of Laboratory, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United StatesIntroductionCryofibrinogen-associated glomerulonephritis (CF-GN) is a rare disease that lacks comprehensive research and requires further investigation to improve our understanding of its pathophysiology.MethodsBased on the morphological findings from a kidney biopsy and blood tests, an elderly patient was diagnosed with CF-GN. Biological materials obtained from peripheral blood were utilized to treat cultured mesangial cells and mice.ResultsThe patient presented with nephrotic syndrome and chronic kidney failure. The biopsy revealed a membranoproliferative glomerulonephritis pattern with distinct substructures and positive fibrinogen staining. Cryofibrinogen was detectable under cold conditions, and monoclonal immunoglobulin (MIg) was exclusively identified within cryoprecipitates. Genetic analysis uncovered an intronic mutation. The patient partially responded to immunosuppressive therapy, but later relapsed with paraproteinemia, and the MIg was detected to have cryoactivity. To investigate the pathophysiology of CF-GN further, its cryoactivity was detected when mixing the serum (with or without MIg) with healthy control plasma. When exposed to the patient’s cryoprecipitates, cultured mesangial cells showed significant proliferation, phagocytosis of fibrinogen, and lysosomal degeneration. Injection of these cryoprecipitates into mice induced proliferative glomerulonephritis and other organ damage.ConclusionThis study provides valuable insights into the diagnosis, treatment, and pathophysiology of CF-GN with paraproteinemia. The identification of the complex of cryofibrinogen and MIg as a potential mechanism of glomerular damage shed light on the pathogenesis of this rare disease.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576917/fullcryofibrinogen-associated glomerulonephritismembranoproliferative glomerulonephritismonoclonal gammopathy of renal significanceanimal modelcell culture |
| spellingShingle | Xuanli Tang Mengya Jiang Huaqin Zhang Peng Bi Jun Wang Tian Ye Jie Zheng Mengli Tong Xingyu Zhu Xiaotao Hou Shuhua Bao Yi Lin Xue Jiang Hongyu Chen Feng Wan Haichun Yang Cryofibrinogen-associated glomerulonephritis with paraproteinemia Frontiers in Immunology cryofibrinogen-associated glomerulonephritis membranoproliferative glomerulonephritis monoclonal gammopathy of renal significance animal model cell culture |
| title | Cryofibrinogen-associated glomerulonephritis with paraproteinemia |
| title_full | Cryofibrinogen-associated glomerulonephritis with paraproteinemia |
| title_fullStr | Cryofibrinogen-associated glomerulonephritis with paraproteinemia |
| title_full_unstemmed | Cryofibrinogen-associated glomerulonephritis with paraproteinemia |
| title_short | Cryofibrinogen-associated glomerulonephritis with paraproteinemia |
| title_sort | cryofibrinogen associated glomerulonephritis with paraproteinemia |
| topic | cryofibrinogen-associated glomerulonephritis membranoproliferative glomerulonephritis monoclonal gammopathy of renal significance animal model cell culture |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1576917/full |
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