Feghali-Bostwick Carol, Medsger Thomas A, Wright Timothy M
Division of Pulmonary, Allergy, and Critical Care Medicine and Simmons Center for Interstitial Lung Disease, University of Pittsburgh, 628 NW Montefiore, Pittsburgh, PA 15261, USA.
Arthritis Rheum. 2003 Jul;48(7):1956-63. doi: 10.1002/art.11173.
To examine concordance for systemic sclerosis (SSc) in monozygotic (MZ) and dizygotic (DZ) twins.
MZ and DZ twins were recruited nationwide. Zygosity was confirmed by DNA fingerprint analysis. The presence of antinuclear antibodies (ANAs) was determined using indirect immunofluorescence with HEp-2 cells as substrate. Identification of SSc-associated serum autoantibodies was performed by immunoprecipitation and double immunodiffusion. Major histocompatibility complex class II alleles were identified by polymerase chain reaction-restriction fragment length polymorphism analysis.
Concordance for SSc was found to be similar in MZ and DZ twins. Overall concordance for SSc was low in the twins (4.7%). Concordance for the presence of ANAs was significantly higher in MZ twins compared with DZ twins. SSc-associated serum autoantibodies occurred exclusively in patients with SSc. The distribution of SSc-associated serum autoantibodies was similar to that observed in our large database of SSc patients. Increased HLA allele sharing was detected in DZ twins, irrespective of disease concordance.
These results indicate that inherited genetic factors are not sufficient to explain the development of SSc. Rather, these data indicate that inheritance may play a role in the development of serum autoantibodies in the "healthy" twin sibling of an SSc patient.
研究单卵双胎（MZ）和双卵双胎（DZ）中系统性硬化症（SSc）的一致性。
在全国范围内招募MZ和DZ双胞胎。通过DNA指纹分析确认合子性。以人喉癌上皮细胞（HEp-2细胞）为底物，采用间接免疫荧光法测定抗核抗体（ANA）的存在情况。通过免疫沉淀和双向免疫扩散鉴定与SSc相关的血清自身抗体。通过聚合酶链反应-限制性片段长度多态性分析鉴定主要组织相容性复合体II类等位基因。
发现MZ和DZ双胞胎中SSc的一致性相似。双胞胎中SSc的总体一致性较低（4.7%）。与DZ双胞胎相比，MZ双胞胎中ANA存在的一致性显著更高。与SSc相关的血清自身抗体仅出现在SSc患者中。与SSc相关的血清自身抗体的分布与我们在大型SSc患者数据库中观察到的相似。在DZ双胞胎中检测到HLA等位基因共享增加，与疾病一致性无关。
这些结果表明，遗传因素不足以解释SSc的发病机制。相反，这些数据表明，遗传可能在SSc患者的“健康”双胞胎同胞血清自身抗体的产生中起作用。
