Nakken Britt, Bodolay Edit, Szodoray Peter
Institute of Immunology, Rikshospitalet, Oslo University Hospital, Sognsvannsveien 20, Oslo, Norway, N-0027.
Department of Clinical Immunology, Institute of Medicine, University of Debrecen Medical and Health Science Centre, Debrecen, Hungary.
Clin Rev Allergy Immunol. 2015 Oct;49(2):152-62. doi: 10.1007/s12016-014-8452-9.
Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions, a quantitative and qualitative impairment of regulatory T cells has been shown previously, and in parallel, a relative dominance of pro-inflammatory Th17 cells has been introduced. Moreover, the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of interleukin (IL)-6, IL-12, IL-17, IL-23, and interferon (IFN)-γ were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression toward serious systemic autoimmune diseases. Moreover, the early targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.
未分化结缔组织病（UCTD）是一种独特的临床实体，是公认的系统性自身免疫性/风湿性疾病的潜在先兆。UCTD的特征是存在各种临床症状以及多种自身抗体，类似于系统性自身免疫性疾病。由于这些患者中约有三分之一最终会转变为典型的系统性自身免疫性/风湿性疾病，因此评估导致这种进展的致病因素至关重要。鉴于UCTD和系统性自身免疫性疾病的血清学和临床特征非常相似，推测类似的致病因素使这两种疾病持续存在。在系统性自身免疫性疾病中，先前已显示调节性T细胞存在定量和定性损伤，同时，促炎性Th17细胞相对占优势。此外，调节性T细胞和Th17细胞之间的失衡在UCTD的发生和发展中起关键作用。此外，我们描述了一种细胞因子失衡，这种失衡导致从UCTD阶段到完全发展的系统性自身免疫性疾病阶段的T细胞内环境稳态出现偏差。白细胞介素（IL）-6、IL-12、IL-17、IL-23和干扰素（IFN）-γ水平病理性升高，同时IL-10水平降低。我们认为，评估Th17/Treg细胞比值以及同时定量细胞因子可能为UCTD早期阶段提供一种有用的诊断工具，以识别有更高几率连续进展为严重系统性自身免疫性疾病的患者。此外，在这些患者中进行早期靶向免疫调节治疗可能会在出现伴有器官损伤的严重自身免疫性疾病之前减缓甚至阻止这种进展。
