Abstract：
OBJECTIVE: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.
METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
RESULTS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren\'s syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
CONCLUSIONS: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
RESULTS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren\'s syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
CONCLUSIONS: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
摘要：
目的：估计抗Ro52-kDa/SSA（TRIM21）自身抗体在系统性硬化症（SSc）中的全球患病率，并描述相关的临床表型，通过对我们法国队列的已发表报告和新数据进行系统评价和荟萃分析。
方法：在一项包括里尔大学医院300名患者的横断面研究中评估了抗TRIM21血清阳性和相关的SSc特征。在Pubmed和Embase中对文献进行了系统回顾，接下来是荟萃分析，使用患病率数据，SSc患者的临床/人口统计学/生物学特征以及用于检测抗TRIM21抗体的分析类型(PROSPEROn°CRD42021223719).
结果：在横断面研究中，抗TRIM21抗体患病率为26%[95CI:21;31]。抗着丝粒抗体是与抗TRIM21共存的最常见的SSc特异性自身抗体。具有抗TRIM21抗体的患者更常见为女性（91％vs77％，p=0.006),更有可能出现相关的干燥综合征(31%vs11%，p<0.001)，肺动脉高压（PAH）的发生率较高（21%vs9%，p=0.017）和更多的消化道并发症，如吞咽困难（20％比9％，p=0.038）或恶心/呕吐（18%vs5%，p=0.009）比抗TRIM21阴性患者。共11,751例SSc患者的35篇文章被纳入荟萃分析。在这个人群中,抗TRIM21抗体的总体血清阳性率为23%[95CI:21;27]，具有高度异质性(I2:93%Phet:<0.0001)，部分由检测方法解释。抗TRIM21血清阳性与女性呈正相关(OR:1.60[95CI:1.25,2.06]),有限的皮肤子集（OR：1.29[1.04，1.61]），关节表现（OR：1.33[1.05，1.68]），肺动脉高压（PH）（OR：1.82[1.42，2.33]），和间质性肺病（ILD）（OR：1.31[1.07，1.60]）。
结论：抗TRIM21抗体经常与通常的SSc抗体共存，但与心肺并发症的高风险独立相关。因此，在评估发生PH和ILD的风险时，应考虑这些自身抗体的存在。值得对患者进行适当的筛查和随访进一步研究。
方法：在一项包括里尔大学医院300名患者的横断面研究中评估了抗TRIM21血清阳性和相关的SSc特征。在Pubmed和Embase中对文献进行了系统回顾，接下来是荟萃分析，使用患病率数据，SSc患者的临床/人口统计学/生物学特征以及用于检测抗TRIM21抗体的分析类型(PROSPEROn°CRD42021223719).
结果：在横断面研究中，抗TRIM21抗体患病率为26%[95CI:21;31]。抗着丝粒抗体是与抗TRIM21共存的最常见的SSc特异性自身抗体。具有抗TRIM21抗体的患者更常见为女性（91％vs77％，p=0.006),更有可能出现相关的干燥综合征(31%vs11%，p<0.001)，肺动脉高压（PAH）的发生率较高（21%vs9%，p=0.017）和更多的消化道并发症，如吞咽困难（20％比9％，p=0.038）或恶心/呕吐（18%vs5%，p=0.009）比抗TRIM21阴性患者。共11,751例SSc患者的35篇文章被纳入荟萃分析。在这个人群中,抗TRIM21抗体的总体血清阳性率为23%[95CI:21;27]，具有高度异质性(I2:93%Phet:<0.0001)，部分由检测方法解释。抗TRIM21血清阳性与女性呈正相关(OR:1.60[95CI:1.25,2.06]),有限的皮肤子集（OR：1.29[1.04，1.61]），关节表现（OR：1.33[1.05，1.68]），肺动脉高压（PH）（OR：1.82[1.42，2.33]），和间质性肺病（ILD）（OR：1.31[1.07，1.60]）。
结论：抗TRIM21抗体经常与通常的SSc抗体共存，但与心肺并发症的高风险独立相关。因此，在评估发生PH和ILD的风险时，应考虑这些自身抗体的存在。值得对患者进行适当的筛查和随访进一步研究。
