Biomarkers of lymphoma in Sjogren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: Results of a multicenter study
Biomarkers of lymphoma in Sjogren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: Results of a multicenter study
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DOI：
10.1016/j.jaut.2013.10.002
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发表时间：
2014-06-01
影响因子：
12.8
通讯作者：
De Vita, Salvatore
中科院分区：
文献类型：
--
作者：
Quartuccio, Luca;Isola, Miriam;De Vita, Salvatore
目的：通过区分涎腺肿胀和冷球蛋白血小球性血管炎(CV)这两种最常见的非恶性淋巴瘤前疾病，确定与原发性干燥综合征(PSS)淋巴组织增殖相关的生物标志物。患者符合以下标准：(1)PSS的AEG标准阳性，(2)血清冷球蛋白检测，(3)无丙型肝炎病毒感染。对B细胞性非霍奇金淋巴瘤(B细胞性非霍奇金淋巴瘤)、无淋巴瘤的慢性非霍奇金淋巴瘤(CV)、无非霍奇金淋巴瘤的涎腺肿大(SW)、无非霍奇金淋巴瘤或淋巴瘤前病变的PSS患者进行多项式分析。结果：共研究661例PSS患者。第1组NHL患者40例(6.1%)，第2组CV17/661例(2.6%)，第3组SW180/661例(27.2%)，第4组PSS对照组424例(64.1%)。低C4[相对风险比(RRR)8.3]、冷球蛋白(RRR 6.8)、抗La抗体(RRR 5.2)和白细胞减少(RRR 3.3)是区分第1组/NHL与第4组/对照组的变量。至于淋巴瘤前疾病患者的亚群，这些生物标志物的缺失为涎腺肿胀患者中98%的淋巴瘤提供了阴性预测值(组3/西南)。对系统性红斑狼疮患者的其他随访研究证实，当至少2/4的生物标志物呈阳性时，淋巴瘤的风险很高。结论：通过解剖PSS相关淋巴瘤前病变的队列，在一系列特征良好的PSS患者中定义了与淋巴瘤相关的生物标志物。值得注意的是，首次证明在有唾液肿胀的PSS患者中，只有那些生物标记物阳性的患者才会增加淋巴瘤演变的风险。(C)2013爱思唯尔有限公司。保留所有权利。
Objectives: To define the biomarkers associated with lymphoproliferation in primary Sjogren's syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV).Methods: A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions.Results: Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive.Conclusions: Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution. (C) 2013 Elsevier Ltd. All rights reserved.