[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Recommendations for diagnosis and treatment of systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

[Clinical characteristics of 37 antiphospholipid syndrome patients complicated by autoimmune hemolytic anemia].

Objective: We sought to investigate the clinical characteristics and risk factors of antiphospholipid syndrome (APS) complicated by autoimmune hemolytic anemia (AIHA). Methods: Retrospective anaysis.Three hundred fifteen consecutive patients with APS were enrolled at the Department of Rheumatology of Peking Union Medical College Hospital between May 2017 to May 2021, and their clinical manifestations[including initial symptoms, time interval between APS onset and diagnosis, systemic lupus erythematosus(SLE), thrombotic events, obstetric morbidity, and extra-criteria manifestations] and laboratory test results[including blood routine, antiphospholipid antibodies(aPLs), blood lipid profile, homocysteine, anti-nuclear antibody profile, immunoglobulin levels, and complement levels] were collected. Then, univariate and multivariate logistic regression analyses were performed. Clinical features and risk factors were analyzed using univariable and multivariable logistic regression analysis. Results: Among 315 APS patients, 37 cases (11.7%) were complicated by AIHA, and AIHA was the first manifestation or co-occurrence. The median time interval between APS onset and diagnosis was 12 months. The proportion of SLE in APS patients combined with AIHA was higher than that in APS patients without AIHA[62.2%(23/37) vs. 19.4%(54/278), P<0.001]. There was no significant difference in the proportions of thrombosis and pregnancy morbidity between the two groups. In terms of extra-criteria manifestations, APS patients with AIHA had a significantly (P<0.05) greater risk of thrombocytopenia (OR=6.19, 95%CI 2.81-13.65) and higher proportions of hypocomplementemia, a positive lupus anticoagulant (LA) result, double aPLs positivity[i.e., any two of the following antibodies were positive: LA, anticardilolipin antibody(aCL), and anti-ß2 glycoprotein Ⅰ(ß2GPⅠ)], and triple aPLs positivity (i.e., LA, aCL, and anti-ß2GPⅠ antibodies were all positive). Multivariate logistic regression analysis showed that SLE (OR=3.46,95%CI 1.60-7.48), thrombocytopenia (OR=2.56,95%CI 1.15-5.67), and hypocomplementemia (OR=4.29,95%CI 2.03-9.04) were independent risk factors for the complication of APS. In the primary APS subgroup, multivariate logistic regression analysis showed that livedo reticularis (OR=10.51,95%CI 1.06-103.78), thrombocytopenia (OR=3.77, 95%CI 1.23-11.57), and hypocomplementemia (OR=5.92,95%CI 1.95-17.95) were independent risk factors for the complication of APS. Conclusions: AIHA is not rare in APS patients; moreover, it occurs more frequently in APS secondary to SLE and is more likely to present with a variety of extra-criteria manifestations. Patients with AIHA should be promptly tested for antiphospholipid antibody profiles and alerted to the possibility of thrombotic events.

[Analysis of differentially expressed microRNA and protein expression profiles carried by exosomes in the plasma of patients with Takayasu's arteritis].

Objective: To detect the microRNAs (miRNAs) and proteins carried by exosomes in the plasma of patients with newly diagnosed Takayasu's arteritis (TAK) and analyze their possible roles in the pathogenesis of TAK. Methods: Ten patients with newly diagnosed TAK from the Department of Rheumatology and Immunology, Peking Union Medical College Hospital were selected during June-November 2020. Five healthy controls were matched with five patients by age and sex. RNA sequencing and protein mass spectrometry were used to detect miRNAs and proteins, respectively, carried by exosomes in the plasma. Differentially expressed miRNAs (DE-miRNAs) and proteins (DEPs) were screened. Thereafter, hierarchical cluster analysis, function, signal pathway, and protein domain enrichment analysis of DE-miRNAs and DEPs were performed. Finally, miRNAs and proteins related to vasculitis and autoimmunity were identified. The possible roles of the miRNAs and proteins in the pathogenesis of TAK were explored. Enumeration data were compared using Fisher's exact probability test or Chi-square test, and a P-value<0.05 was considered significant. Results: Compared with the healthy controls, patients with TAK had 29 DE-miRNAs on their plasma exosomes. Among these DE-miRNAs, miR-101-3p, miR-122-5p, miR-143-3p, miR-185-3p, miR-192-5p, miR-194-5p, miR-19a-3p, miR-19b-3p, miR-20b-5p, miR-21-5p, miR-22-3p, miR-335-5p, miR-34a-5p, miR-3613-5p, miR-548ad-5p, miR-590-3p, and miR-7-5p were upregulated; whereas miR-1249-3p, miR-141-3p, miR-199a-5p, miR-199b-5p, miR-200a-3p, miR-200c-3p, miR-204-5p, miR-29c-5p, miR-335-3p, miR-381-3p, miR-4433b-5p, and miR-584-5p were downregulated. Finally, miR-34a-5p, miR-200c-3p, miR-143-3p, miR-22-3p, and miR-21-5p were identified. Among the 357 DEPs screened, 236 DEPs were upregulated, whereas 121 DEPs were downregulated. Finally, kallikrein B1 (KLKB1), kininogen 1 (KNG1), desmoplakin (DSP) were identified. Conclusion: MiR-34a-5p, miR-200c-3p, miR-143-3p, miR-22-3p, miR-21-5p, KLKB1, KNG1, and DSP carried by exosomes in plasma might participate in the pathogenesis of TAK by regulating vascular physiology, inflammation, autoimmunity, and other processes. They may be biomarkers and therapeutic targets of TAK.

[The analysis to data from Chinese Rheumatism Data Center external quality assurance program for autoantibodies in 2021].

To evaluate the data obtained from the external quality assurance program initiated by Chinese Rheumatism Data Center (CRDC-QAP) for autoantibodies detection in 2021, so as to assess the consensus and differences in cross-laboratory testing to autoantibodies in China. This is a retrospective study. After collecting data from the first half year (from May 15th to July 10th) and the second half year (from August 15th to November 19th) of CRDC-QAP program for autoantibody detection in 2021, it firstly analyzed the qualitative consensus of the cross-laboratory results. Secondly, it compared the positivity grade of numeric results according to the Sample to cut-off ratio (S/CO ratio) calculation. Finally, the mean and coefficient variation (CV) of numeric results from three major manufacturers were calculated. A total of 303 and 332 clinical labs voluntarily participated in the first half year and the second half year of CRDC-QAP program for autoantibody detection in 2021, respectively. Except for anti-ß2 glycoprotein type I (aß2-GPI) IgM, the cross-laboratory consensus of qualitative results for the other autoantibodies is greater than 96%. As for anti-cyclic citrullinated peptide antibody (anti-CCP) and anti mitochondrial antibody-M2 (AMA-M2), the numeric results from more than 90% laboratories showed the same positivity grade. More than 50% of laboratories used chemiluminescence immunoassay (CLIA) for quantitative evaluation of autoantibody. The CV of numeric results from different manufacturers showed certain differences(P<0.01) with the range from 0 to 238%. Although high consensus can be observed in term of qualitative result for autoantibody detection in cross-laboratory, there are still certain differences in numeric results in term of positivity grade and manufacturer-based CV.

[Recommendations for the diagnosis and treatment of connective tissue disease associated pulmonary arterial hypertension in China].

Pulmonary arterial hypertension (PAH) is a clinicopathological syndrome caused by the increase of pulmonary artery, and it is the most serious complication of connective tissue disease (CTD). In recent years, a lot of progress has been made in the diagnosis, treatment and evaluation of PAH. Chinese Rheumatology Association formulated this recommendation on the basis of current experience and guidelines, in order to promote early screening, early diagnosis and early intervention of CTD-PAH, as well as patient follow-up and management, to improve the prognosis of CTD-PAH patients.

[The 498th case: rash, fever and hematuria].

A 50-year-old man was admitted to the Department of Rheumatology at Peking Union Medical College Hospital with rash for 6 months, and fever and hematuria for 5 months. The main clinical manifestations included fever, fatigue, purpura, hematuria and thrombocytopenia. He was positive for antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and rheumatoid factor (RF), and had low complement levels. Initial blood culture, echocardiography and chest CT showed no signs of infection. Diagnosis of connective tissue disease was made initially. His disease improved under treatment with glucocorticoids and immunosuppressive agents, but relapsed when glucocorticoids were tapered. After admission, the diagnosis was reconsidered, and infective endocarditis was finally diagnosed with repeated positive blood cultures and vegetations detected by transesophageal echocardiography. Amoxicillin and clavulanate potassium were initiated, and surgery was performed. His symptoms finally recovered gradually.

[The clinical characteristics of nuclear dense fine speckled pattern in 95 289 patients].

To investigate the distribution and clinical significance of nuclear dense fine speckled (DFS) pattern in various diseases. A total of 95 289 patients who received DFS tests at Peking Union Medical College Hospital from January 2019 to December 2020 were included in this study. The results of indirect immunofluorescence assay (IIF) for detection of antinuclear antibody (ANA) were evaluated. The positive rates of ANA and DFS were 39.60% (37 733/95 289) and 1.19% (1 139/95 289) respectively. The positive rate of DFS in ANA-positive patients was 3.02% (1 139/37 733). DFS and ANA positivity were significantly different among different age groups rather than gender. The positivity rate of DFS reached the peak (55.57%, 633/1 139) in young patients between 21-40 years, while positive ANA with negative DFS was mainly observed in patients between 41-60 years (37.26%, 13 636/36 594). Additionally, single ANA-positivity were mainly detected in rheumatology department (59.23%, 18 402/31 066), whereas positive DFS was more common in obstetrics and gynecology department (3.08%, 49/1 593). There were 82.88% (944/1 139) patients with positive DFS diagnosed with non-autoimmune disease (non-AID), and 19.49%(222/1 139) with dermatosis. Positive DFS with higher titer (≥1∶320) was detected more frequently in autoimmune disease (AID) patients (5.13%, 10/195) than in non-AID patients (1.69%, 16/944) (P<0.05). The DFS pattern is rare in ANA positive patients, which is mainly observed in women between 21-49 years. High titer of DFS is prevalent in AID patients, but positive DFS is detected more in non-AID patients, especially those with dermatosis.

[Association of skin lesion severity with clinical features of psoriatic arthritis].

Objective: To investigate the relationship between psoriasis severity and clinical features in psoriatic arthritis (PsA). Methods: Patients were recruited from the Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021, and data were collected including the baseline demographic characteristics, various clinical manifestations (including arthritis, nail disease, comorbidities), laboratory tests[including erythrocyte sedimentation rate(ESR), C-reactive protein (CRP)], health assessment questionnaire (HAQ). Body surface area (BSA) and psoriasis area and severity index (PASI) were selected for the tools of assessment of cutaneous psoriasis. Patients were divided to two groups, including the severe psoriasis group (BSA>10%) and the non-severe psoriasis group (BSA≤10%). Disease assessment included ankylosing spondylitis disease activity score (ASDAS), disease activity score 28 (DAS28) and disease activity in psoriatic arthritis (DAPSA). Results: 1 074 eligible patients with PsA were recruited, and 106 (9.9%) had severe psoriasis. Compared with non-severe psoriasis group, the severe psoriasis group had more peripheral joint involvement (including patients with ever or current peripheral arthritis, 94.3% vs. 85.6%), more polyarticular joint involvement (including patients with current peripheral arthritis, 74.0% vs. 58.2%), more axial joint involvement (51.4% vs. 39.9%), more nail disease (72.6% vs. 61.4%), more frequency of smoking (20.2% vs. 18.7%), and higher proportion of hypertension (23.4% vs. 14.4%). In addition, the severe psoriasis group had higher level of ESR [33(10, 70) mm/1h vs. 20(9, 38) mm/1h] and CRP [18.6(5.0, 60.8) mg/L vs. 7.0(2.4, 18.1) mg/L], higher values of DAS28-ESR (4.5±1.7 vs. 3.7±1.5), DAS28-CRP (4.2±1.5 vs. 3.4±1.4), ASDAS-ESR (3.5±1.4 vs. 2.6±1.2), and ASDAS-CRP(3.4±1.6 vs. 2.5±1.2), higher scores of HAQ [0.6(0.1, 1.0) vs. 0.3(0.0, 0.8)]. Conclusion: Patients with PsA with severe psoriasis bore a heavier disease burden. Therefore, clinicians were supposed to pay more attention to them. In addition to skin lesions, they should also focus on examination of other clinical manifestations, such as joints and nails.