Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Department of Hematology, Peking University People's Hospital, Beijing, China.
Clin Rheumatol. 2018 Jul;37(7):1751-1762. doi: 10.1007/s10067-018-4064-8. Epub 2018 Mar 13.
To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551-197.435), P = 0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.
分析风湿性疾病患者单克隆丙种球蛋白血症（MG）的临床谱、实验室特征和转归。2010 年 1 月至 2017 年 7 月，对 872 例风湿性疾病住院患者进行了 MG 筛查。共纳入 41 例患者。描述了他们的临床和生物学特征以及结局。对于每例原发性干燥综合征（pSS）患者，选择 2 例年龄和性别匹配且无 MG 的 pSS 患者作为对照。评估了 MG 存在和恶性血液病的危险因素。SS、类风湿关节炎、系统性红斑狼疮、强直性脊柱炎、原发性胆汁性肝硬化、多发性肌炎、低肌病性皮肌炎、银屑病关节炎、ANCA 相关性血管炎、多发性大动脉炎和风湿性多肌痛患者均可出现 MG，其中 SS 最常见。37 例患者检测到血清 M 蛋白。血清中鉴定出的单克隆带为 16 个 IgG（5κ，11λ）、11 个 IgA（6κ，5λ）、6 个 IgM（5κ，1λ）和 4 个游离λ链。另外 4 例患者尿液中出现 M 成分。高 ESR、白蛋白/球蛋白倒置、类风湿因子阳性、高丙种球蛋白血症和低补体血症是常见特征，超过一半的 41 例患者存在这些特征。pSS 患者并发 MG 时，尿 NAG 异常发生率较高（71.4%比 15.8%，P=0.025），ESR[55.0（53.5）mm/h 比 21.0（31.8）mm/h，P=0.001]、ESSDAI[26.0（25.0）比 12.0（9.0），P=0.006]和 ClinESSDAI 评分[24.0（25.0）比 10.5（10.0），P=0.011]较高。多变量分析显示，疾病活动度（ESSDAI 调整比值比 1.127（95%CI 1.015-1.251），P=0.025；ClinESSDAI 调整比值比 1.121（95%CI 1.011-1.242），P=0.030）是 MG 存在的唯一独立危险因素。随访期间，2 例患者出现一过性血清 M 蛋白，2 例发生同种型转换，1 例进展为多发性骨髓瘤（MM），另有 2 例出现单克隆或多克隆浆细胞间质浸润导致的肾损伤。41 例 MG 患者中有 7 例（17.1%）出现血液系统肿瘤，4 例为 MM，2 例为冒烟型 MM，1 例为黏膜相关淋巴组织（MALT）型 B 细胞淋巴瘤。轻链 MG 与 MM 的发生相关（OR 17.5（95%CI 1.551-197.435），P=0.041），但与淋巴瘤或 SMM 的发生风险增加无关。MG 可见于各种风湿性疾病患者，以 SS 最常见。MG 存在可能与更高的疾病活动度相关。在此情况下可见包括 MM 和淋巴瘤在内的血液系统肿瘤的发生。因此，我们建议在需要时对风湿性疾病患者进行 MG 筛查和密切监测潜在恶性转化。
