Chun Li

探究合并胎儿心脏病变的抗干燥综合征相关抗原A(Sjögren’s-syndrome-related antigen A, SSA)抗体阳性孕妇的临床表现、实验室指征及药物特征。 在2013年1月至2023年7月于北京大学人民医院就诊且最终确诊自身免疫病的孕妇中, 选择抗SSA抗体阳性且超声确诊胎儿心脏病变的患者作为病变组, 抗SSA抗体阳性且超声检查无胎儿心脏病变的患者作为对照组, 收集两组患者的临床、实验室及用药信息, 比较组间基线数据无差异后对其临床指标进行统计学分析。 合并胎儿心脏病变的抗SSA抗体阳性患者共11例, 其中有先天性房室传导阻滞表现者共7例, 是最常见的胎儿心脏病变类型。病变组患者孕前确诊自身免疫病的比例显著低于对照组(P=0.032), 多因胎儿心脏病变首次进行相关免疫学检查。病变组患者孕期白细胞水平[(9.29±2.58)×10⁹/L vs. (7.10±1.90)×10⁹/L, t=3.052, P=0.004]、红细胞沉降率[49.50(48.00, 51.00) mm/h vs. 23.00(15.00, 30.25) mm/h, Z=-2.251, P=0.024]、IgA水平[3.46(2.30, 5.06) g/L vs. 2.13(1.77, 2.77) g/L, Z=-2.181, P=0.029]、抗核抗体(antinuclear antibody, ANA)滴度[1∶320(1∶160, 1∶320) vs. 1∶80(1∶40, 1∶160), Z=-3.022, P=0.003]显著高于对照组。组间孕期合并SSB抗体阳性的比例(37.5% vs. 7.7%, P=0.053)、羟氯喹使用剂量及起用时间差异均无统计学意义。病变组孕期使用激素的比例及剂量显著高于对照组(P＜0.05), 其中孕早期两组间差异无统计学意义, 而孕中期、孕晚期病变组激素使用剂量显著高于对照组。 胎儿心脏病变是一种罕见但与抗SSA抗体阳性高度相关的胎儿畸形, 孕期白细胞、红细胞沉降率、IgA水平及ANA滴度显著升高的患者胎儿心脏病变发生的风险更高。胎儿房室传导阻滞一旦发生便难以逆转, 因此, 预防和监测的重要性高于补救治疗。

Objective To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). Methods A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2 years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. Results The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud’s phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). Conclusions This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.

Objective: Infections have been implicated in rheumatoid arthritis (RA) development. However, the impact of premorbid infection on initiation and perpetuation of RA has not been well elucidated. Thus, we sought to conduct a large scale on-site survey to study whether premorbid infection may trigger RA and influence status of the disease. Methods: Premorbid infectious events were collected in cohort of 902 RA patients from December 2015 to June 2016. Type of infections prior to RA onset and its possible effects on disease status were analyzed. Result: Three hundred and thirty-four out of 902 patients (37.03%) experienced infections within one month preceding RA onset. The most frequent infections were respiratory (16.08%), intestinal (11.09%) and urinary tract (9.87%) infection, respectively. The infection was associated with increased disease activity. Early onset was found in patients with urinary infection. High disease activity risk was increased in patients who pre-exposure to urinary infection (OR=3.813, 95%CI=1.717-12.418) and upper respiratory infection (OR=2.475, 95%CI= 0.971-6.312). Conclusion: Pre-exposure infections are associated with development of RA. Severe disease status of RA and persistent of active disease status are related to preceding infections.

Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which T cells play a pivotal role in the pathogenesis. Knowledge in terms of the CD4 T-cell transcriptome in RA is limited. The aim of this study was to examine the whole-genome transcription profile of CD4 T cells in RA by comparing patients with RA to healthy controls. Methods: Peripheral blood CD4 T cells were isolated from 53 RA patients with active disease and 45 healthy individuals; 13 cases and 10 controls were enrolled in microarray analysis. The remaining 40 cases and 35 controls were recruited as an independent cohort for the validation study. Bioinformatics was performed on Gene Ontology (GO), gene-gene interaction networks, and pathway analysis. The gene modules, by combining the results from GO, gene networks, and pathway analysis, were selected for further validation. Results: The CD4 T cells showed 1,496 differentially expressed (DE) genes in RA patients relative to healthy individuals. GO analysis revealed that the DE genes were enriched in immune response, T-cell response, apoptosis process, and Wnt receptor signaling. Pathway analysis also identified that ‘Wnt signaling pathway’ was differentially regulated between two groups (P = 2.78 × 10⁻¹⁰). By gene-gene network analysis, we found that the DE genes were enriched in T-cell receptor (TCR), JAK-STAT signaling, and Wnt signaling pathway. By gene module analysis, we found that a number of DE genes overlapped in the three different analyses. In total, 23 genes were selected for further validation, and nine genes were confirmed. Of these, four genes (SOCS3, CBL, IFNAR1, and PIK3CA) were involved in STAT3 (signal transducer and activator of transcription 3) signaling, and three genes (CBL, KLF9, and CSNK2A1) were involved in the Wnt signaling pathway. Additionally, several zinc finger transcription factors (ZEB1, ZNF292, and ZNF644) were confirmed. Conclusions: We report here the first case–control study of the CD4 T-cell transcriptome profile in RA. Our data provide evidence that CD4 T cells from patients with RA have abnormal functional networks in STAT3 signaling and Wnt signaling. Our results also suggest that the aberrant expression of several zinc finger transcription factors (ZEB1, ZNF292, and ZNF644) may be potential pathogenic factors for RA.

Introduction: Interleukin (IL)-33 is a proinflammatory cytokine contributing to the pathogenesis of rheumatoid arthritis (RA). The gene encoding IL-33 may serve as a genetic factor and be associated with the risk of RA. To investigate the potential association between IL33 and RA, we performed a case–control study based on Chinese Han population. Methods: A three-stage case–control study was performed. Two tag single-nucleotide polymorphisms (SNPs) (rs7044343 and rs10975514), mapping to the IL33 gene, were first genotyped in the discovery population. We further genotyped rs7044343 and rs10975514 in the validation and replication population. The associations between the two tag SNPs and phenotypic subgroups of RA and levels of serum IL-33 were assessed with a logistic regression model. Results: In the discovery population, the CC genotype of rs7044343 was associated with RA patients (odds ratio (OR) = 0.777, 95% confidence interval (CI), 0.611 to 0.988; P = 0.040). After anti-citrullinated peptide antibody (ACPA) stratification, the CC genotype of rs7044343 was also shown to be a protective genotype in RA without ACPA (OR = 0.610; 95% CI, 0.379 to 0.982; P = 0.042). In the validation population and replication population, the association between rs7044343 and RA, especially ACPA-negative RA, was still significant. A meta-analysis of discovery, validation, and replication panels confirmed the association between CC genotype of rs7044343 and RA (P_combined = 0.0004; OR_combined = 0.77; 95% CI, 0.67 to 0.89). No evidence was found for heterogeneity between three sample sets (P _het = 0.99; I² = 0%). Similar results were also obtained in ACPA-negative RA (P_combined = 0.0002; OR_combined = 0.57; 95% CI, 0.43 to 0.77). No association was detected between rs10975514 polymorphism and RA susceptibility in the discovery and validation population. The serum levels of IL-33 were significantly lower in the patients with the rs7044343 CC genotype. Conclusion: The CC genotype of rs7044343 in IL33 is associated with RA patients and downregulates IL-33 expression in RA.