Ma Tiantian, Wang Hui, Su Tao, Wang Suxia
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
Front Med (Lausanne). 2022 Feb 10;9:813439. doi: 10.3389/fmed.2022.813439. eCollection 2022.
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 IgMκ; however, the cryoprecipitate contained monoclonal IgMκ and polyclonal IgG, as well as immunoglobulins κ and λ. 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 IgMκ, 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 IgMκ were not detected. This is a special presentation of CLL/SLL with monoclonal IgMκ, 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.
慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）是一种产生肾毒性单克隆免疫球蛋白（MIg）的单克隆B细胞淋巴细胞增多症。然而，MIg在CLL中的作用及其如何影响CLL患者的生存仍不清楚。在此，我们报告一例与CLL相关的具有肾脏意义的单克隆免疫球蛋白血症（MGRS）病例。一名59岁的中国女性因腹痛、皮肤紫癜和典型的酱油色尿入院检查。实验室检查显示她患有微血管病性溶血性贫血、血小板减少、急性肾损伤（AKI）和补体减少。她还报告两年前有冷球蛋白血症、血栓性微血管病（TMA）和AKI。当时的外周血涂片显示4%的裂体细胞、库姆斯试验阴性和乳酸脱氢酶（LDH）升高。基于补体介导的TMA诊断，患者接受了血浆置换治疗并实现了临床疾病缓解。然而，血清补体4降低和冷球蛋白血症持续存在。进一步检查显示B淋巴细胞升高和单克隆血清IgMκ；然而，冷沉淀物包含单克隆IgMκ和多克隆IgG，以及免疫球蛋白κ和λ。血浆置换后，她的LDH、血小板和补体3（C3）水平恢复正常。骨髓活检和肿大的锁骨下淋巴结活检显示为CLL/SLL。肾脏病理结果显示小动脉内皮细胞有明显的黏液样水肿和肾小球内皮细胞肿胀，然而未观察到血栓形成、冷球蛋白形成和血管炎。我们还发现轻度系膜增生性C3肾小球肾炎和肾间质CLL细胞浸润。总体而言，这些临床和病理表现归因于单克隆IgMκ，其触发了C3激活。最终确诊为与CLL相关的MGRS。给予了六个周期的利妥昔单抗、环磷酰胺、长春新碱和地塞米松治疗，之后她接受了伊布替尼治疗。患者病情缓解，血清C4水平恢复正常。未检测到冷球蛋白和IgMκ。这是CLL/SLL伴有单克隆IgMκ的一种特殊表现，属于MGRS的一种类型。MIg激活补体系统导致了伴有C3肾小球肾炎的TMA。应及时启动针对TMA和CLL/SLL的治疗以改善患者预后。
