Chatzis Loukas G, Pezoulas Vasilis, Voulgari Paraskevi V, Baldini Chiara, Exarchos Themis P, Fotiadis Dimitrios I, Mavragani Clio P, Skopouli Fotini N, Moutsopoulos Haralampos M, Tzioufas Athanasios G, Goules Andreas V
Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, and Institute for Autoimmune, Systemic and Neurological Diseases, Athens, Greece.
Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Greece.
Clin Exp Rheumatol. 2021 Nov-Dec;39 Suppl 133(6):80-84. doi: 10.55563/clinexprheumatol/47a4kr. Epub 2021 Oct 4.
To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity.
From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed.
One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients.
Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.
描述合并血清学阴性的干燥综合征（SS）患者的临床谱。
从符合2016年美国风湿病学会（ACR）-欧洲抗风湿病联盟（EULAR）分类标准的连续性SS患者的多中心研究人群中，回顾性识别出三联血清阴性[抗Ro/SSA（-）、抗La/SSB（-）、类风湿因子（RF）（-）和抗核抗体（ANA）（+）]和四联血清阴性[抗Ro/SSA（-）、抗La/SSB（-）、RF（-）和ANA（-）]的患者。这两组患者与2个不同的对照SS组按1:1比例匹配：i）经典抗Ro/SSA血清阳性患者[SS（+）]和ii）类风湿因子阴性的经典抗Ro/SSA血清阳性患者[SS（+）/RF（-）]，以探讨其对疾病表现的影响。比较临床、实验室和组织学特征。还对三联和四联血清阴性的SS患者进行了比较。
135例SS患者（8.6%）被确定为三联血清阴性患者，72例（4.5%）为四联血清阴性患者。与SS（+）对照组相比，三联血清阴性患者外周神经受累频率较低（0%对7.2%，p = 0.002），间质性肾病频率较低，口干患病率高于SS（+）/RF（-）对照组。与SS（+）对照组相比，四联血清阴性患者持续性淋巴结病（1.5%对16.9%，p = 0.004）和淋巴瘤（0%对9.8%，p = 0.006）的发生率较低，与SS（+）/RF（-）SS对照组相比，持续性淋巴结病的患病率较低（1.5%对15.3%，p = 0.008），干眼（98.6%对87.5%，p = 0.01）和自身免疫性甲状腺炎（44.1%对17.1%，p = 0.02）的发生率较高。研究组比较分析显示，与四联血清阴性患者相比，三联血清阴性患者持续性淋巴结病和淋巴瘤的发生率较高，灶性评分较高，SS诊断年龄较晚。
合并血清学阴性占SS总人群的近9%，并与较轻的临床表型相关，部分归因于类风湿因子的缺乏。
