Gottenberg Jacques-Eric, Busson Marc, Loiseau Pascale, Cohen-Solal Julien, Lepage Virginia, Charron Dominique, Sibilia Jean, Mariette Xavier
Service de Rhumatologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM EMI 0109, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
Arthritis Rheum. 2003 Aug;48(8):2240-5. doi: 10.1002/art.11103.
To reevaluate, in a large series of patients with Sjögren's syndrome (SS) recruited from 2 French centers, the question of whether HLA is associated with SS itself or with a pattern of secretion of autoantibodies.
One hundred forty-nine white patients fulfilling the American-European Consensus Group criteria for SS were divided into 3 subgroups, according to their anti-Ro/SSA and anti-La/SSB status, as follows: group 1 (n = 53), no antibody; group 2 (n = 46), anti-SSA only; group 3 (n = 50), both anti-SSA and anti-SSB. Patients were compared with 222 unrelated healthy subjects representative of the white population in France.
Comparisons between the 149 SS patients and 222 controls confirmed the association of SS with DRB103 (the frequency was 25% in patients versus 10% in controls) and DQB102 (32% versus 22%). The association between HLA and SS was restricted to patients with anti-SSA and/or anti-SSB; no association with HLA was observed in patients in group 1 (no antibody). The frequency of HLA-DRB115 was highest in group 2 (24%), compared with 11% in group 1 and 11% in controls, whereas the frequency of HLA-DRB103 was highest in group 3 (44%), compared with 12% in group 1, 19% in group 2, and 10% in controls. Group 2 and group 3 had more clinical and biologic markers of activity than did group 1 but were not clinically different. HLA alleles were not associated with clinical features of the disease, and were associated with only some biologic features: rheumatoid factor positivity, increased serum IgG, and thrombocytopenia were associated with HLA-DRB103, and neutropenia was associated with DQB101.
HLA class II markers confer genetic susceptibility to Sjögren's syndrome. The association between HLA and SS is restricted to patients with anti-SSA and/or anti-SSB antibodies; HLA is not associated with SS in patients without these autoantibodies. The absence of a difference in disease severity between groups 2 and 3, as well as the restricted association of HLA-DRB1*03 in group 3, strongly suggest that HLA alleles predispose to autoantibody secretion, without being associated with clinical outcome. HLA class II phenotype might support epitope spreading: HLA-DR15 favors anti-SSA synthesis, whereas HLA-DR3 is associated with both anti-SSA and anti-SSB production.
在从法国两个中心招募的一大系列干燥综合征（SS）患者中，重新评估HLA是与SS本身相关还是与自身抗体分泌模式相关的问题。
149例符合美国 - 欧洲共识小组SS标准的白人患者，根据其抗Ro/SSA和抗La/SSB状态分为3个亚组，如下：第1组（n = 53），无抗体；第2组（n = 46），仅抗SSA；第3组（n = 50），抗SSA和抗SSB均阳性。将患者与222名代表法国白人人群的无关健康受试者进行比较。
149例SS患者与222名对照之间的比较证实了SS与DRB103（患者中的频率为25%，对照中为10%）和DQB102（32%对22%）相关。HLA与SS的关联仅限于抗SSA和/或抗SSB的患者；第1组（无抗体）患者中未观察到与HLA的关联。HLA - DRB115的频率在第2组中最高（24%），而第1组中为11%，对照组中为11%；HLA - DRB103的频率在第3组中最高（44%），第1组中为12%，第2组中为19%，对照组中为10%。第2组和第3组比第1组有更多的临床和生物学活动标志物，但在临床上无差异。HLA等位基因与疾病的临床特征无关，仅与一些生物学特征相关：类风湿因子阳性、血清IgG升高和血小板减少与HLA - DRB103相关，而中性粒细胞减少与DQB101相关。
HLA II类标志物赋予干燥综合征遗传易感性。HLA与SS的关联仅限于抗SSA和/或抗SSB抗体的患者；无这些自身抗体的患者中HLA与SS无关。第2组和第3组在疾病严重程度上无差异，以及第3组中HLA - DRB1*03的有限关联，强烈表明HLA等位基因易导致自身抗体分泌，而与临床结局无关。HLA II类表型可能支持表位扩展：HLA - DR15有利于抗SSA合成，而HLA - DR3与抗SSA和抗SSB产生均相关。
