TH17在结缔组织病相关性间质性肺病中的意义

目的探讨外周血Th17及IL-17在结缔组织病相关性间质性肺疾病的表达及意义。方法收集23例正常对照组及28例病理类型为非特异性间质性肺炎(NSIP)的结缔组织病相关性间质性肺疾病(CTD-ILD)患者的外周血单个核细胞及血浆,分别检测PBMC中Th17的比例及血浆中IL-17的表达情况,并收集入组患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)数据。结果与正常对照组相比,CTD-ILD患者组Th17比例明显增加,差别具有统计学意义(P0.05),CTD-ILD患者IL-17细胞因子的浓度较正常对照组的血浆浓度明显增加(P0.01)。但CTD-ILD患者外周血Th17及IL-17与患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)之间均无显著相关性。结论在CTD-ILD患者体内Th17及其细胞因子IL-17明显升高,可能参与疾病的发生。     

KL-6和Th1/Th2细胞因子在结缔组织病相关性间质性肺炎中的表达及临床意义

目的探讨涎液化糖链抗原(KL-6)与1型辅助性T细胞/2型辅助性T细胞(Th1/Th2)细胞因子在结缔组织病相关性间质性肺炎(CTD-IP)中的表达及临床意义。 方法选择2017.01至2019.01间收治的77例CTD-IP患者纳为CTD-IP组,60例无肺间质病变CTD者纳为CTD组,50例健康体检合格者为健康组,比较三组血清涎液化糖链抗原(KL-6)、Th1细胞因子γ干扰素(IFN-γ)、Th2细胞因子白介素-4(IL-4)及Th1/Th2(IFN-γ/IL-4)水平,并根据CTD-IP患者肺通气障碍、肺弥散功能障碍严重程度及影像学表现,对CTD-IP组患者进行分组,统计CTD-IP患者血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4表达水平,并分析以上血清物质在评估CTD-IP患者病情中的效果。 结果健康对照组、CTD组及CTD-IP组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者肺通气轻度障碍组、中度障碍组及重度障碍组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者肺弥散轻度障碍组、中度障碍组及重度障碍组中,血清KL-6及IL-4水平呈依次上升趋势,IFN-γ及IFN-γ/IL-4水平呈依次下降趋势,组间差异均显著(P<0.05);CTD-IP患者HRCT表现活动性组血清KL-6、IFN-γ、IFN-γ/IL-4水平明显高于非活动性组(P<0.05),IL-4水平显著低于非活动性组(P<0.05)。 结论血清KL-6、IFN-γ、IL-6及IFN-γ/IL-6水平在反映CTD-IP患者肺通气功能障碍、肺弥散功能障碍、疾病活动期中具有良好应用价值,可作为反映CTD-IP患者病情的可靠血清参考物质。     

结缔组织病所致间质性肺疾病的研究进展

结缔组织病（CTD）包括许多种疾病,如红斑狼疮、硬皮病、类风湿关节炎、干燥综合征、皮肌炎/多发性肌炎及血管炎等。间质性肺病多发生于CTD中,其中早期表现为肺泡炎,而晚期则表现为弥漫性肺间质纤维化,病程终末期可出现呼吸衰竭,因为其发生率和病死率较高,目前已成为研究热点。该病病因和发病机制复杂,预后及治疗方法和效果取决于组织病理类型、风湿病的基础情况及相关的肺动脉高压。本文就CTD所致间质性肺病的现代认识进行综述。     

关注结缔组织病相关间质性肺疾病

结缔组织病（connective tissues disease,CTD）是风湿性疾病中的一大类,常累及全身多个系统,表现为慢性炎症性自身免疫病,当侵犯呼吸系统时,可出现间质性肺疾病（interstitial lung disease,ILD）、胸膜炎和肺动脉高压等,见表1。CTD与ILD同时存在时,常称为结缔组织病相关间质性肺     

结缔组织病合并间质性肺疾病的研究进展

间质性肺疾病普遍发生于结缔组织病中，因为它的发生率和病死率较高，目前已成为研究的热点。近几年，在病理分型方法、诊断和治疗方面，结缔组织病合并间质性肺疾病有了一些新的进展．在此作一综述。     

结缔组织病相关间质性肺疾病的临床研究进展

结缔组织病（CTD）是一组累及全身多系统的慢性炎症性自身免疫病,其共同病理变化为淋巴细胞致敏产生免疫损伤,导致血管壁、间质的纤维素样坏死性炎症及随后引起多脏器的胶原纤维增生。由于肺间质、肺血管、支气管及胸膜均富含疏松结缔组织和血液供应,CTD常累及肺和胸膜,引起间质性肺疾病（ILD）、肺血管炎和胸膜炎等。     

结缔组织病相关性间质性肺疾病的诊治进展

结缔组织病（CTD）是一组累及全身多系统的自身免疫病,合并间质性肺疾病（ILD）较为常见,导致肺功能障碍、低氧血症,严重影响患者的生活质量和预后。不同CTD显示出异质性的ILD类型。CTD-ILD常见的影像学和组织病理学类型是非特异性间质性肺炎、机化性肺炎和普通型间质性肺炎。大部分CTD-ILD表现为缓慢进展的肺损伤,少数患者短期内急剧进展且预后不良。CTD-ILD目前主要应用糖皮质激素和／或免疫抑制剂治疗,生物制剂显示出临床疗效,尚需随机临床试验证实。部分ILD患者具有自身免疫病的特征,不足以诊断为某种特定的CTD,应予以密切随访。     

结缔组织病相关间质性肺病与自身抗体的相关性研究进展

间质性肺疾病(ILD)是结缔组织病(CTD)的重要并发症之一,结缔组织病相关间质性肺病(CTD-ILD)的发病率和病死率较高,并且早期确诊有一定困难,CTD-ILD与自身抗体相关性的研究对其预防、早期确诊、指导治疗及预后极为重要.为了便于临床能正确诊断和及时治疗CTD-ILD,现将常见于CTD的自身抗体及CTD患者发生ILD的临床特点进行综述.     

028 Th1/Th2反应与人类肺部疾病

Th1/Th2平衡消长是机体免疫反应调节的基本方式,并已成为近年来的研究热点之一.本文综述了主要肺部疾病中Th1/Th2反应的研究进展,有助于深入了解其免疫学致病机理和探索新的治疗方法.     

以肺部结缔组织病变为首发的间质性肺病1例及文献复习

特发性间质性肺炎（idiopathic interstitial pneumonia,IIP）是一组以肺间质和肺泡腔具有不同形式和程度的炎症和纤维化为主要病理特征的疾病。     

超声在结缔组织病相关肺间质病变中的应用

肺是结缔组织病(connective tissue disease,CTD)的重要靶器官,可出现肺动脉高压(pulmonary hypertension,PAH)、肺泡出血、肺间质病变(interstitial lung disease,ILD)等多种表现,其中ILD是一类以炎症和不同程度纤维化为主要表现的弥漫性肺损伤。目前有多种方式来评估ILD的类型、范围及严重程度。     

305例结缔组织病相关间质性肺病临床特点分析

目的分析结缔组织病相关间质性肺病(Connective tissue disease associated interstitial lung disease,CTD-ILD)临床特征。方法回顾性分析305例西京医院临床免疫科CTD-ILD的临床特征及类风湿关节炎间质性肺病(Rheumatoid arthritis associated interstitial lung disease,RA-ILD)和干燥综合征间质性肺病(Sjogren's syndrome associated interstitial lung disease,p SS-ILD)患者胸部高分辨CT特点。结果 CTD患者ILD的发病率为11.78%,其中多发性肌炎相关ILD的发病率最高(53.13%),其次为抗中性粒细胞胞浆抗体相关性血管炎(40.74%)、混合结缔组织病(35.14%)和硬皮病(29.73%)。p SS-ILD和RA-ILD在CTD-ILD中所占比例最大,分别为24.92%和23.61%,两者约占所有CTD-ILD的一半。结论 CTD患者ILD的发病率高,RA-ILD和p SS-ILD是CTD-ILD的主要疾病,加强对CTD-ILD的早期筛查和早期治疗非常重要。     

Performance of the St George’s Respiratory Questionnaire in patients with connective tissue disease‐associated interstitial lung disease

Background and objective

The St George’s Respiratory Questionnaire (SGRQ) is a self‐administered questionnaire used to assess health‐related quality of life (HRQoL) in various chronic respiratory diseases. Few studies have assessed the performance of the SGRQ in patients with connective tissue disease‐associated interstitial lung disease (CTD‐ILD). We aimed to examine the SGRQ’s performance characteristics and generate data to support its reliability and validity in patients with CTD‐ILD.

Methods

We used data from 193 CTD‐ILD patients evaluated at Tosei General Hospital from May 2007 to July 2016 to assess the cross‐sectional and longitudinal validity of the SGRQ.

Results

The mean age of the patients was 64.2 years and 122 (63.2%) were women. There were no significant differences in SGRQ scores between any of the CTD groups. Internal consistency (Cronbach’s α = 0.905) and repeatability (intraclass correlation coefficient (ICC) = 0.873) for the SGRQ total score were excellent. At baseline, SGRQ total score was significantly associated with clinically meaningful measures of physiological function, exercise capacity and dyspnoea. Change in SGRQ total score over 6 months was also associated with change in other measures. Cox proportional hazards models showed that higher baseline SGRQ total score was a significant predictor of mortality. The estimated minimal clinically important difference of SGRQ total score was 4–13 points.

Conclusion

These data support the validity and reliability of SGRQ as a sensitive measure for capturing HRQoL in patients with CTD‐ILD.

     

Increased serum concentration of BAFF/APRIL and IgA2 subclass in patients with mixed connective tissue disease complicated by interstitial lung disease

Abstract

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD?). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD? patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF–APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD? patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD? patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD.     

Anti-MDA5 antibody dermatomyositis-associated rapidly progressive interstitial lung disease patient complicated with mixed connective tissue disease: A case report

Anti-MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP-ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71-year-old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti-Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti-MDA5⁺DM-RP-ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite “triple therapy” for RP-ILD. This case illustrates that patients with coexisting anti-MDA5⁺DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti-Ro52 antibodies.     

Idiopathic interstitial pneumonias with connective tissue diseases features: A review

A systematic approach is recommended to search for clinical and biological features of connective tissue disease (CTD) in any patient with interstitial lung disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be considered particularly in women and subjects younger than 50 years, and in those with an imaging and/or pathological pattern of non‐specific interstitial pneumonia. However, the diagnosis of CTD may be difficult when ILD is the presenting or the dominant manifestation of CTD. A proportion of patients with ILD present symptoms that belong to the spectrum of CTD and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some imaging and histopathological patterns may also suggest the presence of an underlying CTD. Although studies published to date used heterogeneous definitions and terminology for this condition, evidence is accumulating that even limited CTD features are relevant regarding symptoms, imaging features, pathological pattern and possibly evolution to overt CTD, whereas the impact on prognosis needs confirmation. Conversely, autoantibodies alone do not seem to impact the prognosis or management in patients with otherwise typical idiopathic pulmonary fibrosis and no extra‐pulmonary manifestation. A collective international multidisciplinary effort has proposed a uniform definition and criteria for ‘interstitial pneumonia with autoimmune features’, a condition characterized by limited CTD features occurring in the setting of ILD, with the aim of fostering future clinical studies. Referral of ILD patients suspect to have CTD to a rheumatologist and possibly multidisciplinary discussion may contribute to a better management.