{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:21:00Z","timestamp":1761218460261,"version":"3.41.2"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL) is a monoclonal B cell lymphocytosis that produces nephrotoxic monoclonal immunoglobulin (MIg). However, the role of MIg in CLL and how it affects CLL patient survival are still unknown. Here, we report a case of MIg with renal significance (MGRS) associated with CLL. A 59-year-old Chinese woman complaining of abdominal pain, skin purpura, and typical soy-colored urine was admitted to the hospital for investigation. Laboratory tests revealed that she had microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury (AKI), and hypocomplementemia. She also reported cryoglobulinemia, thrombotic microangiopathy (TMA), and AKI 2 years previously. Peripheral blood smears at that time showed 4% schistocytes, a negative Coombs' test, and elevated lactate dehydrogenase (LDH). Based on a diagnosis of complement-mediated TMA, the patient was treated by plasmapheresis and achieved clinical disease remission. However, the serum hypocomplement 4 and cryoglobulinemia persisted. Further investigation showed elevated B lymphocytes and monoclonal serum IgM\u03ba; however, the cryoprecipitate contained monoclonal IgM\u03ba and polyclonal IgG, as well as immunoglobulins \u03ba and \u03bb. After plasmapheresis, her LDH, platelets, and complement 3 (C3) levels returned to normal. Biopsies of the bone marrow and an enlarged subclavicular lymph node revealed CLL\/SLL. Renal pathological findings indicated significant arteriolar endothelial cells myxoid edema and glomerular endothelial cells swelling, however no thromboli, cryoglobulin formation and vasculitis were observed. We also found mild mesangial proliferative C3 glomerulonephritis and renal interstitial CLL cells infiltration. Collectively, these clinical and pathological manifestations were attributed to monoclonal IgM\u03ba, which triggered C3 activation. MGRS associated with CLL was finally confirmed. Six cycles of rituximab, cyclophosphamide, verodoxin, and dexamethasone therapy were administered, after which she received ibrutinib. The patient experienced disease remission, and her serum C4 level returned to normal. Cryoglobulin and IgM\u03ba were not detected. This is a special presentation of CLL\/SLL with monoclonal IgM\u03ba, which is a type of MGRS. Activation of the complement system by MIg led to TMA with C3 glomerulonephritis. Treatment for TMA and CLL\/SLL should be initiated in a timely manner to improve patient prognosis.<\/jats:p>","DOI":"10.3389\/fmed.2022.813439","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T07:24:45Z","timestamp":1644477885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis"],"prefix":"10.3389","volume":"9","author":[{"given":"Tiantian","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.blre.2014.12.001","article-title":"The mystery of chronic lymphocytic leukemia (CLL): why is it absent in Asians and what does this tell us about etiology, pathogenesis and biology?","volume":"29","author":"Yang","year":"2015","journal-title":"Blood Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/ckj\/sfy026","article-title":"Renal involvement in chronic lymphocytic leukemia","volume":"11","author":"Wanchoo","year":"2018","journal-title":"Clin Kidney J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.3324\/haematol.2015.128793","article-title":"Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience","volume":"100","author":"Strati","year":"2015","journal-title":"Haematologica."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5302","DOI":"10.1182\/blood.V122.21.5302.5302","article-title":"Renal disease in patients with chronic lymphocytic leukemia (CLL)","volume":"122","author":"Shanafelt","year":"2013","journal-title":"Blood."},{"key":"B5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41581-018-0077-4","article-title":"The evaluation of monoclonal gammopathy of renal significance: a consensus report of the international kidney and monoclonal gammopathy research group","volume":"15","author":"Leung","year":"2019","journal-title":"Nat Rev Nephrol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13000-021-01120-4","article-title":"The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia\/small lymphocytic lymphoma from a large single Chinese center","volume":"16","author":"Wang","year":"2021","journal-title":"Diagn Pathol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.leukres.2010.12.005","article-title":"Prognostic significance of serum immunoglobulin paraprotein in patients with chronic lymphocytic leukemia","volume":"35","author":"Xu","year":"2011","journal-title":"Leuk Res."},{"key":"B8","first-page":"795","article-title":"Prognostic significance of serum immunoglobulin paraprotein in chronic lymphocytic leukemia","volume":"33","author":"Yang","year":"2012","journal-title":"Zhonghua Xue Ye Xue Za Zhi."},{"key":"B9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.trsl.2006.11.001","article-title":"Serum-free light chain-a new biomarker for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia","volume":"149","author":"Martin","year":"2007","journal-title":"Transl Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1111\/bjh.16975","article-title":"Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia","volume":"190","author":"Corbingi","year":"2020","journal-title":"Br J Haematol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1309\/2A0FL1HM5PN2510P","article-title":"Lymphoid neoplasms associated with IgM paraprotein: a study of 382 patients","volume":"123","author":"Lin","year":"2005","journal-title":"Am J Clin Pathol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.1182\/blood-2006-02-005488","article-title":"Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma","volume":"108","author":"Chng","year":"2006","journal-title":"Blood."},{"key":"B13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/leu.2014.198","article-title":"IgM peak independently predicts treatment-free survival in chronic lymphocytic leukemia and correlates with accumulation of adverse oncogenetic events","volume":"29","author":"Rizzo","year":"2015","journal-title":"Leukemia."},{"key":"B14","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1136\/jmg.2006.045328","article-title":"Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome","volume":"44","author":"Servais","year":"2007","journal-title":"J Med Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/ki.2012.212","article-title":"C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up","volume":"82","author":"Sethi","year":"2012","journal-title":"Kidney Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.kint.2018.01.037","article-title":"C3 Glomerulopathy-associated with a Monoclonal Ig is a distinct subtype","volume":"94","author":"Ravindran","year":"2018","journal-title":"Kidney Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.2215\/CJN.06180710","article-title":"Fre'meaux-Bacchi V. Glomerulonephritis with isolated C3 deposits and monoclonal gammopathy: a fortuitous association?","volume":"6","author":"Bridoux","year":"2011","journal-title":"Clin J Am Soc Nephrol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1053\/j.ajkd.2013.02.370","article-title":"C3 Glomerulonephritis associated with Monoclonal Gammopathy","volume":"62","author":"Zand","year":"2013","journal-title":"Am J Kidney Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1084\/jem.175.4.939","article-title":"Activation of the alternative pathway of complement by monoclonal lambda light chains in membranoproliferative glomerulonephritis","volume":"175","author":"Meri","year":"1992","journal-title":"J Exp Med."},{"key":"B20","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.4049\/jimmunol.163.8.4590","article-title":"Nephritogenic lambda light chain dimer: a unique human miniautoantibody against complement factor H","volume":"163","author":"Jokiranta","year":"1999","journal-title":"J Immunol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.813439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T13:10:14Z","timestamp":1674738614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.813439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":20,"alternative-id":["10.3389\/fmed.2022.813439"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.813439","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,2,10]]},"article-number":"813439"}}