Stathopoulou E A, Routsias J G, Stea E A, Moutsopoulos H M, Tzioufas A G
Department of Pathophysiology, School of Medicine, University of Athens, Greece.
Clin Exp Immunol. 2005 Jul;141(1):148-54. doi: 10.1111/j.1365-2249.2005.02812.x.
Coxsackie virus RNA has recently been detected in biopsy specimens of minor salivary glands from patients with primary Sjögren's Syndrome (pSS). A peptide derived from Coxsackie virus 2B protein (pepCoxs) presents 87% sequence homology with the 222-229 region of the major linear B-cell epitope of Ro60 kD autoantigen (pep216-232). Synthetic peptides corresponding to pep216-232: (216)KALSVETEKLLKYLEAV(232) and pepCoxs: (31)MVTSTITEKL LKNLVKI(47), were prepared. Sera from 42 patients with pSS and 43 patients with systemic lupus erythematosus (SLE) as well as sera from 27 healthy individuals (normal controls) and sera from 30 patients with rheumatoid arthritis (disease controls) were tested against the two homologous peptides. Twenty-five percent of SLE sera and 33.3% of pSS sera reacted against pep216-232, whereas 28% of SLE sera and 37% of pSS sera recognized the pepCoxs. The sera reacting with pep216-232 were apparently the same as those reacting with pepCoxs. Normal sera and disease control sera presented only a limited reactivity against both peptides (ranging from 3.7% to 10%). Both peptides reacted more prominently with anti-Ro/La (+) sera from pSS patients. Thus, pep216-232 was recognized by 17% of the anti-Ro (+) sera and by 42% of the anti-Ro/La (+) sera, whereas pepCoxs was recognized by 28.5% and 38% of the a-Ro(+) and a-Ro/La(+) sera, respectively. Purified anti-pep216-232 antibodies readily reacted with both peptides while inhibition experiments revealed the specificity of this reaction. These results suggest a possible cross-reaction between antibodies to the major linear B-cell epitope of Ro60 kD autoantigen and the homologous pepCoxs in pSS patients. This cross-reaction might potentially play a role in autoantibody formation and the perpetuation of the autoimmune response against Ro/SSA and La/SSB.
最近在原发性干燥综合征(pSS)患者的小唾液腺活检标本中检测到柯萨奇病毒RNA。一种源自柯萨奇病毒2B蛋白的肽(pepCoxs)与Ro60 kD自身抗原主要线性B细胞表位(pep216 - 232)的222 - 229区域具有87%的序列同源性。制备了与pep216 - 232相对应的合成肽:(216)KALSVETEKLLKYLEAV(232)和pepCoxs:(31)MVTSTITEKL LKNLVKI(47)。对42例pSS患者、43例系统性红斑狼疮(SLE)患者的血清以及27名健康个体(正常对照)和30例类风湿关节炎患者(疾病对照)的血清进行了这两种同源肽的检测。25%的SLE血清和33.3%的pSS血清与pep216 - 232发生反应,而28%的SLE血清和37%的pSS血清识别pepCoxs。与pep216 - 232发生反应的血清显然与与pepCoxs发生反应的血清相同。正常血清和疾病对照血清对这两种肽的反应都很有限(范围为3.7%至10%)。两种肽与pSS患者的抗Ro/La(+)血清反应更明显。因此,pep216 - 232被17%的抗Ro(+)血清和42%的抗Ro/La(+)血清识别,而pepCoxs分别被28.5%和38%的抗Ro(+)和抗Ro/La(+)血清识别。纯化的抗pep216 - 232抗体很容易与这两种肽发生反应,而抑制实验揭示了这种反应的特异性。这些结果表明,pSS患者中针对Ro60 kD自身抗原主要线性B细胞表位的抗体与同源的pepCoxs之间可能存在交叉反应。这种交叉反应可能在自身抗体形成以及针对Ro/SSA和La/SSB的自身免疫反应持续存在中发挥作用。