[Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome].

OBJECTIVE: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome. METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis. RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%. CONCLUSION: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

[Anti-endothelial cell antibodies in predicting early miscarriage].

OBJECTIVE: To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage. METHODS: A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women. RESULTS: (1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035). CONCLUSION: Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: A case-control study.

To determine the prevalence of pulmonary complications in primary Sjögren syndrome (pSS), and to identify the risk factors and the prognosis associated with pulmonary involvement in pSS patients.A total of 1341 hospitalized patients (853 with pSS and 488 with secondary Sjögren syndrome [sSS]) were retrospectively reviewed. Of these, 165 hospitalized patients with pSS-associated interstitial lung disease (ILD) were analyzed and recruited as a study group. Eighty-four pSS patients without organ damage were included as a control group.One hundred and sixty-five patients (19.34%) from the pSS group and 126 patients (25.82%) from the sSS group presented with lung involvement. Of the 165 pSS patients with lung complications, 151 (91.5%) were women. The mean age was 61.25 ±â€Š9.79 years, and the median disease duration was 84 (24-156) months. Non-specific interstitial pneumonia (NSIP; 39.1%) was the predominant pattern on high-resolution computed tomography (HRCT). The total HRCT score was 9.71 ±â€Š4.77. Impairment in diffusion capacity was the most common (74.3%) and severe complication (predicted value of TLCO was 57.5 ±â€Š21.2%). The 5-year survival rate for all patients with pSS-ILD was 88.5%. Age, disease duration, rheumatoid factor (RF), and C-reactive protein (CRP) were significantly higher than in controls, whereas anti-SSA was less common. Age, RF, and CRP were independent predictors of ILD after adjustment for confounders.Lung involvement is a common and severe complication of Sjögren syndrome. Age and disease activity are correlated with pulmonary involvement in pSS patients.

Antilymphocyte antibodies in systemic lupus erythematosus: association with disease activity and lymphopenia.

PURPOSE: We analyzed the prevalence, clinical correlation, and the functional significance of ALA in patients with systemic lupus erythematosus (SLE). METHODS: ALA IgG was detected by indirect immunofluorescence in the serum of 130 SLE patients, 75 patients with various rheumatic diseases, and 45 healthy controls (HC). RESULTS: The sensitivity and specificity of ALA IgG in SLE were 42.3% and 96.7%, respectively. ALA was observed in 55.6% (50/90) of patients with lymphopenia, which was significantly higher than in patients with normal lymphocytes (5/40, 12.5%; P<0.001). Patients with active SLE showed higher ALA positivity (60.9%) than those with inactive disease (24.2%; χ2=17.925; P<0.001). ALA correlated significantly with hypocomplementemia, anti-dsDNA antibodies, and higher SLEDAI scores. The incidences of ALA in SLE patients who were seronegative for anti-dsDNA, anti-Sm, or both antibodies were 32.9% (26/79), 41.0% (43/105), and 32.4% (22/68), respectively. The ALA-positive group also had higher incidences of neuropsychiatric SLE (NPSLE) and lupus nephritis (LN). In multivariate analyses, ALA was independently associated with lymphopenia, higher SLEDAI scores, and increased risk for LN. ALA titers significantly decreased as clinical disease was ameliorated following treatment. CONCLUSIONS: ALA occurred more frequently in patients with active SLE and was independently associated with lymphopenia, disease activity, and LN.

[Significance of anti-citrullinated human papilloma virus-47 E2(345-362) peptide antibodies in diagnosis of early-stage rheumatoid arthritis].

OBJECTIVE: To investigate the prevalence and the diagnostic values of antibodies to the citrullinated HPVP in early-stage rheumatoid arthritis. METHODS: Antibodies against HPVP and citrullinated HPVP were detected by ELISA in the sera of 101 patients with early-stage RA, 149 patients with other rheumatic diseases and 40 healthy controls. The prevalence and diagnostic values of these antibodies for early-stage RA were analyzed by statistical software. RESULTS: (1)The prevalence of IgG, IgM antibodies to citrullinated HPVP in early-stage RA were significantly higher than that in the patients with other rheumatic diseases as well as in the healthy individuals.(2)The diagnostic sensitivity of IgG and IgM citrullinated HPVP antibodies in early-stage RA were 62.4% and 66.3% respectively and the specificity value of the two antibody isotypes were 88.7% and 89.6%,similar to that of the anti-CCP antibody. (3)The positivity rates of IgG and IgM antibodies against citrullinated HPVP were 59.4% and 71.9% in IgM-RF negative early-stage RA patients, and 39.4% and 51.5% in anti-CCP antibody negative early-stage RA patients. (4) The DAS28 score [ IgG (6.3±1.0) vs. (5.6±0.9), P=0.002; IgM (6.2±1.1) vs. (5.6±0.8), P=0.008] , X-ray stages (IgG 56.1% vs. 21.2%, P=0.001;IgM 50.9% vs. 29.4%, P=0.036),anti-CCP antibodies(IgG 96.8% vs. 55.3%, P=0.001; IgM 89.6% vs. 64.7%, P=0.023) in citrullinated HPVPP positive patients were higher than those of citrullinated HPVP negative patients. Additionally, the levels of ESR[IgG(70.3±32.4)vs.(51.9±27.8), P=0.004; IgM (67.4±31.5)vs.(53.8±27.7), P=0.035] in citrullinated HPVP positive patients were higher than those of negative patients (P<0.05). CONCLUSION: IgG and IgM antibodies to citrullinated HPVP are highly sensitive and specific novel biomarkers for early-stage RA diagnosis, and are related to disease activity and joint damage.

Toll-like receptor 9 is correlated to disease activity in Chinese systemic lupus erythematosus population.

BACKGROUND: Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE. METHODS: mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA). RESULTS: TLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients. CONCLUSION: TLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.

[Screening for serum specific biomarkers in patients with primary Sjögren's syndrome and interstitial lung disease using proteomic fingerprint techniques].

OBJECTIVE: To detect the serum protein biomarkers and establish a diagnostic model for primary Sjögren's syndrome (pSS) with interstitial lung disease (ILD). METHODS: Serum samples from 69 patients with pSS were prepared with WCX magnetic beads, and analyzed on PBS II-C mass spectrometer reader. Biomarker Wizard software was used to detect protein peaks and potential difference between the patients with pSS-ILD and with non-ILD. The model was developed by Biomarker Patterns software. RESULTS: Totally 7 discriminative mass-to-charge (m/z) ratios were identified to be related with pSS-ILD (P<0.05). Among these, the m/z peaks at 3 778.3, 3 318.3 and 2 236.6 were used to construct a diagnostic model. The sensitivity and specificity of the model were 93.1% and 87.5%, respectively. In a testing set, the sensitivity and specificity of the model were 84.0% and 85.7%, respectively. CONCLUSION: The potential protein biomarkers for pSS-ILD are discovered in the serum by MALDI-TOF-MS combined with WCX magnetic beads. The diagnostic pattern combining 3 778.3, 3 318.3 and 2 236.6 m/z protein peaks can discriminate pSS-ILD and non-ILD.

Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population.

BACKGROUND: A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population. METHODS: We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data. RESULTS: No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population. CONCLUSIONS: Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.

Role of anti-nucleosome antibody in the diagnosis of systemic lupus erythematosus.

OBJECTIVE: To investigate the role of anti-nucleosome antibodies (AnuA) in systemic lupus erythematosus (SLE). METHODS: IgG anti-nucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in the sera of 233 SLE and 220 other rheumatic diseases' patients as well as 31 health controls. The patients were also evaluated for clinical and biological parameters. RESULTS: (1) Out of 233 SLE patients, 144 (61.8%) were seropositive for AnuA, which was significantly higher than that of patients with other rheumatic diseases [2.7% (6/220), P < 0.001]; the sensitivities and specificities of AnuA in SLE were 61.8% and 97.6%, respectively. (2) The positive rated of AnuA in SLE lacking of anti-DNP, anti-cmDNA, anti-Sm and anti-dsDNA antibodies were 57.1%, 55.9%, 62.4% and 51.2%, respectively. (3) The frequency of the fever, skin rash, and arthralgia were significantly higher in 144 positive AnuA SLE than those in AnuA negative SLE (P < 0.05). The frequency of leukopenia, elevations of ESR and CRP, lower C3/C4 levels and proteinuria in AnuA positive groups was significantly higher than that of AnuA negative groups (P < 0.05). (4) Level of AnuA was strongly correlated with the SLEDAI scores (r = 0.385, P < 0.001). Patients with active SLE showed significantly higher positive rate of AnuA (66.1%) than those with inactive disease (45.7%) (chi2 = 6.568, P = 0.010). CONCLUSIONS: AnuA is one of the most valuable markers in the diagnosis of SLE lacking of anti-dsDNA, anti-Sm, anti-DNP and anti-cmDNA antibodies. The level of AnuA is associated with the disease activity of SLE.