Abstract：
OBJECTIVE: Non-Hodgkin\'s lymphoma (NHL) risk assessment is crucial in Sjögren\'s syndrome (SS). We studied the prevalence of clonal immunoglobulin gene rearrangements in minor salivary glands (MSG) and their correlations with lymphoma occurrence and with previously established NHL predictors.
METHODS: Molecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines.
RESULTS: Among 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively.
CONCLUSIONS: The detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors.
METHODS: Molecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines.
RESULTS: Among 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively.
CONCLUSIONS: The detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors.
摘要：
目的：非霍奇金淋巴瘤（NHL）风险评估在干燥综合征（SS）中至关重要。我们研究了小唾液腺（MSG）中克隆性免疫球蛋白基因重排的患病率及其与淋巴瘤发生和先前建立的NHL预测因子的相关性。
方法：对207例疑似SS或SS期间疑似淋巴瘤患者的新鲜冰冻MSG进行了分子B细胞扩增研究，使用标准化的多重PCR分析结合通过微毛细管电泳进行的异源双链分析。克隆病例的分配是基于EuroClonality联盟指南。
结果：在207名研究患者中，31(15%)有MSG单克隆B细胞浸润。与无SS的患者相比，有SS的患者（28/123，22.8%）的单克隆明显更频繁（3/84，3.6%，P<0.001)。SS患者MSG中的单克隆B细胞浸润与正在进行的唾液腺NHL显着相关，唾液腺肿胀，CD4+T淋巴细胞减少,类风湿因子（RF）活性，低补体水平和2型混合型冷球蛋白血症。生物危险因素的积累与较高的MSGB细胞单克隆率相关，因为只有RF阳性的患者没有MSGB细胞单克隆的可能性。具有1或2个其他危险因素的RF阳性患者MSGB细胞单克隆的概率分别为25.0％和85.7％，分别。
结论：通过这种易于执行的分子测定法检测MSG单克隆B细胞扩增是有用的，在诊断时和SS过程中。单克隆B细胞扩增与表现出正在进行的淋巴瘤或其他已确定的淋巴瘤预测因素的SS患者子集相关。
方法：对207例疑似SS或SS期间疑似淋巴瘤患者的新鲜冰冻MSG进行了分子B细胞扩增研究，使用标准化的多重PCR分析结合通过微毛细管电泳进行的异源双链分析。克隆病例的分配是基于EuroClonality联盟指南。
结果：在207名研究患者中，31(15%)有MSG单克隆B细胞浸润。与无SS的患者相比，有SS的患者（28/123，22.8%）的单克隆明显更频繁（3/84，3.6%，P<0.001)。SS患者MSG中的单克隆B细胞浸润与正在进行的唾液腺NHL显着相关，唾液腺肿胀，CD4+T淋巴细胞减少,类风湿因子（RF）活性，低补体水平和2型混合型冷球蛋白血症。生物危险因素的积累与较高的MSGB细胞单克隆率相关，因为只有RF阳性的患者没有MSGB细胞单克隆的可能性。具有1或2个其他危险因素的RF阳性患者MSGB细胞单克隆的概率分别为25.0％和85.7％，分别。
结论：通过这种易于执行的分子测定法检测MSG单克隆B细胞扩增是有用的，在诊断时和SS过程中。单克隆B细胞扩增与表现出正在进行的淋巴瘤或其他已确定的淋巴瘤预测因素的SS患者子集相关。
