Burdt M A, Hoffman R W, Deutscher S L, Wang G S, Johnson J C, Sharp G C
University of Missouri, Columbia, USA.
Arthritis Rheum. 1999 May;42(5):899-909. doi: 10.1002/1529-0131(199905)42:5<899::AID-ANR8>3.0.CO;2-L.
To determine the long-term clinical and immunologic outcomes in a well-characterized cohort of 47 patients with mixed connective tissue disease (MCTD), including reactivity with U small nuclear RNP (snRNP) polypeptides.
Patients were followed up over a period of 3-29 years with immunogenetic and systematic clinical and serologic analysis. Sera were analyzed for reactivity with snRNP polypeptides U1-70 kd, A, C, B/B', and D, for anti-U1 RNA, and for anticardiolipin antibodies (aCL).
The typical core clinical features of MCTD tended to develop over time; features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension, pulmonary dysfunction, and central nervous system disease persisted, following treatment. A favorable outcome was observed in 62% of patients; 38% had continued active disease or had died, with death associated with pulmonary hypertension and aCL. All patients had autoantibodies to the U1-70 kd polypeptide of snRNP, and most were positive for anti-U1 RNA. An orderly progression of intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, as was the novel finding of "epitope contraction" followed by disappearance of anti-snRNP autoantibodies during prolonged remission.
These patients demonstrated the typical immunogenetic, clinical, and serologic findings of MCTD, and the condition rarely evolved into systemic lupus erythematosus or systemic sclerosis. The majority of patients had favorable outcomes, with pulmonary hypertension being the most frequent disease-associated cause of death. Intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, followed by "epitope contraction" and ultimate disappearance of anti-snRNP autoantibodies during prolonged disease remission.
确定47例特征明确的混合性结缔组织病（MCTD）患者的长期临床和免疫学结局，包括与U小核糖核蛋白（snRNP）多肽的反应性。
对患者进行了3至29年的随访，进行免疫遗传学以及系统的临床和血清学分析。分析血清与snRNP多肽U1-70kd、A、C、B/B'和D的反应性、抗U1 RNA以及抗心磷脂抗体（aCL）。
MCTD的典型核心临床特征往往随时间发展；炎症特征以及雷诺现象和食管动力不足有所减轻，而治疗后肺动脉高压、肺功能障碍和中枢神经系统疾病持续存在。62%的患者预后良好；38%的患者疾病持续活动或死亡，死亡与肺动脉高压和aCL相关。所有患者均有针对snRNP的U1-70kd多肽的自身抗体，大多数抗U1 RNA呈阳性。观察到自身抗体对snRNP多肽反应性的分子内扩散有序进展，以及在长期缓解期间出现“表位收缩”并随后抗snRNP自身抗体消失这一新发现。
这些患者表现出MCTD典型的免疫遗传学、临床和血清学表现，且该病很少演变为系统性红斑狼疮或系统性硬化症。大多数患者预后良好，肺动脉高压是最常见的与疾病相关的死亡原因。观察到自身抗体对snRNP多肽反应性的分子内扩散，随后在疾病长期缓解期间出现“表位收缩”以及抗snRNP自身抗体最终消失。
