Profile and clinical relevance of non-criteria antiphospholipid antibodies in patients diagnosed with or highly suspected of APS.

OBJECTIVE: This study investigates the positivity and relevance of non-criteria aPLs with clinical phenotypes in patients highly suspected of or diagnosed with APS. METHODS: Outpatient cases were included from a prospectively maintained database, and patients were grouped into APS (n = 168), seronegative APS (SNAPS, n = 9), those meeting the diagnostic criteria for clinical events without laboratory results (only-event, n = 15), those that had aPL positivity without clinical manifestations (asymptomatic APA, n = 39), and healthy controls (n = 88). Criteria aPL results and APS-related clinical features were extracted. Sixteen non-criteria aPLs were tested and analysed. RESULTS: LA, aCL and anti-ß2 glycoprotein-I were positive in 84.5%, 61.3% and 74.4% of APS patients, and 61.5%, 59.0% and 74.4% of asymptomatic APA patients, respectively. In patients negative for criteria serological tests, 23 out of 24 were positive for at least one non-criteria aPL. Triple-positive patients also had significantly higher tests of some aPLs in comparison with other groups. Stroke was associated with anti-phosphatidyl-inositol (aPI) IgG and anti-phosphatidyl-glycerol (aPG) IgG. Late embryonic loss correlated with aPI IgM, and premature birth/eclampsia was associated with aPI IgG and aPG IgG. There were also positive associations between heart valve lesions and anti-phosphatidylserine-prothrombin (aPS/PT) IgM, APS nephropathy and anti-phosphatidyl-choline IgG or aPS/PT IgG, and livedo reticularis and anti-phosphatidyl-ethanolamine IgM. CONCLUSION: The prevalence of non-criteria aPLs differed from diagnostic biomarkers in patients diagnosed with or suspected of APS. Detection of aPLs provided additive value in the evaluation of APS-related clinical manifestations.

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients.

Background: The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non-criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations. Methods: From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits. Results: The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aß2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391). Conclusion: Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.

The clinical value of indirect immunofluorescence for screening anti-rods and rings antibodies: A retrospective study of two centers in China.

Objective: To investigate the distribution and clinical significance of the rods and rings (RR) pattern in various diseases. Methods: A total of 169,891 patients in Peking Union Medical College Hospital (PUMCH) and 29,458 patients in Inner Mongolia People's Hospital (IMPH) from January 2018 to December 2020 were included, and the results of ANA (antinuclear antibodies) and special antibodies were analyzed retrospectively. Results: The positive rates of ANA and RR patterns were 34.84%, 0.16% in PUMCH, and 44.73%, 0.23% in IMPH. Anti-RR antibodies mainly appear in adults (≥ 41 years), mostly of low or medium fluorescence titers. Isolated RR patterns were mostly presented (60.30% and 69.12%, respectively), and the RR pattern mixed with the speckled pattern was most commonly observed among patients having two or more patterns. The RR pattern existed in a variety of diseases including hepatitis C, AIDs, pulmonary diseases, nephropathy diseases, and even healthy people. The highest prevalence of the RR pattern was observed in hepatic diseases, such as hepatic dysfunction (0.79%), hepatic cirrhosis (1.05%), PBC (0.85%), and AIH (0.65%), etc. The positive rate of specific antibodies in RR pattern cases was 31.25%, and anti-Ro52 (27, 20.61%) was the most common target antibody. Conclusion: The RR pattern had a low prevalence in ANAs test samples and varied in different nationalities and regions. Except for hepatitis C, it could be observed in AIDs, pulmonary diseases, nephropathy, other hepatic diseases, and even healthy people, but the positive rate was slightly higher in hepatic diseases. Its mechanism of action and clinical relevance still need clarification.

The Impact of Authentic Leadership on Innovative Work Behavior: Mediating Roles of Proactive Personality and Employee Engagement.

The purpose of the study is to investigate the impact of authentic leadership and proactive personality on innovative work behavior through dual mediation approach. This study applied a judgment sampling technique and data were gathered from 311 high-tech manufacturing industries of Shenzhen, China. The measurement model and structural model were tested using structural equation modeling technique through AMOS 24 software. The results indicate that authentic leadership has a positive and significant effect on proactive personality. Meanwhile, findings show that proactive personality has a significant impact on innovative work behavior. Moreover, findings show that proactive personality positively mediates the relationship between authentic leadership and innovative work behavior. Furthermore, findings illustrate that work engagement positively mediates the relationship between proactive personality and innovative work behavior. This study provides insightful and valuable implications to high-tech manufacturing industries executives and regulators interested in organizational productivity.

Applications of Protein Microarrays in Biomarker Discovery for Autoimmune Diseases.

Dysregulated autoantibodies and cytokines were deemed to provide important cues for potential illnesses, such as various carcinomas and autoimmune diseases. Increasing biotechnological approaches have been applied to screen and identify the specific alterations of these biomolecules as distinctive biomarkers in diseases, especially autoimmune diseases. As a versatile and robust platform, protein microarray technology allows researchers to easily profile dysregulated autoantibodies and cytokines associated with autoimmune diseases using various biological specimens, mainly serum samples. Here, we summarize the applications of protein microarrays in biomarker discovery for autoimmune diseases. In addition, the key issues in the process of using this approach are presented for improving future studies.

HLA-DPB1 variant rs3117242 is associated with anti-neutrophil cytoplasmic antibody-associated vasculitides in a Han Chinese population.

AIM: The vasculitis diseases granulomatosis with polyangiitis (GPA) and microscopic polyangitis (MPA) are the two major forms of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). A recent genome-wide association study has shown that the genes HLA-DPB1 and HLA-DQ conferred susceptibility to GPA and MPA, respectively. We investigated the linkage between putative AAV-related genes (HLA-DPB1, ARHGAP18, CD226, CTLA-4, MOSPD2 and PRTN3) and AAV in a Han Chinese population. METHOD: A Sequenom MassAarray system (iPLEX assay, Sequenom, San Diego, CA, USA) was used to genotype single nucleotide polymorphisms (SNPs) in 176 Han Chinese patients with AAV (100 with GPA, 76 with MPA) and 485 ethnically matched healthy controls. RESULT: The frequency of the rs3117242 variant T allele (HLA-DPB1) was significantly higher in GPA patients than in the controls (68.0% compared with 50.4%, OR = 2.09, 95% CI: 1.51-2.88, Bonferroni corrected P-value [Pc] = 6.24E-5), but was not significantly different between MPA patients and controls (Pc = 0.14). The same results were obtained via genotype distribution and logistic regression analysis based on three genetic models. The allele and genotype distributions of the other polymorphisms were not significantly associated with AAV patients as a whole or GPA or MPA patients considered separately. CONCLUSION: The rs3117242 of HLA-DPB1 could be considered a genetic risk factor for GPA in Chinese Han people. These findings provide further insights and clues into the etiology of GPA and MPA.

Evaluation of the Clinical Performance of a Novel Chemiluminescent Immunoassay for Detection of Anticardiolipin and Anti-Beta2-Glycoprotein 1 Antibodies in the Diagnosis of Antiphospholipid Syndrome.

Detection of antiphospholipid antibodies represents the first-line approach for diagnosis of antiphospholipid syndrome (APS). In this study, we evaluated the clinical performance of a novel chemiluminescence assay (CIA) in detection of IgG/IgM/IgA anti-cardiolipin (aCL) and IgG/IgM/IgA anti-ß2 glycoprotein 1 (aß2GP1) antibodies and to compare it with commercial enzyme-linked immunosorbent assay (ELISA) kits from the same manufacturer.A total of 227 sera were tested in this study, including 84 samples from patients with APS, 104 samples from patients with non-APS diseases as disease controls, and 39 healthy controls. Serum IgG/IgM/IgA aCL and IgG/IgM/IgA aß2GP1 were determined by both ELISA (QUANTA Lite™ ELISA) and CIA (QUANTA Flash®assays).Significant quantitative correlations were identified between ELISA and CIA in IgG/IgM/IgA aCL and IgG/IgM/IgA aß2GP1 autoantibodies detection (P < 0.001), with the rho value ranging from 0.51 to 0.87. In addition, ELISA and CIA demonstrated good qualitative agreements in IgG/IgM/IgA aCL and IgM/IgA aß2GP1 autoantibodies determination with kappa coefficient ranged from 0.52 to 0.77. In contrast, ELISA and CIA showed a moderate qualitative agreement in IgG aß2GP1 detection with a kappa value of 0.2. Notably, significantly higher IgG aß2GP1 positive sera were detected by CIA, compared to those detected by ELISA in both primary APS (52.9% vs. 8.8%) and APS associated to other diseases sera (70.0% vs. 8.0%). For diagnosis of APS, IgG aß2GP1 detection by CIA (IgG aß2GP1 CIA) demonstrated the highest sensitivity (63.1%), followed by IgG aCL CIA (48.8%). More importantly, IgG aß2GP1 CIA demonstrated the highest ability to predict the thrombotic events in patients with APS, with an OR of 3 (95% CI: 1.1-7.9).Our data suggest that this novel CIA assay had good performance in detecting aCL and aß2GP1 antibodies, especially in the detection of IgG aß2GP1 antibodies. Our findings could shed insight on the application of CIA in the laboratory diagnosis of APS in China.

Single nucleotide polymorphisms in the toll-like receptor 2 (TLR2) gene are associated with microscopic polyangiitis in the northern Han Chinese population.

OBJECTIVES: Our study was designed to evaluate the association of single nucleotide polymorphisms (SNPs) of the TLR2 gene with antineutrophil cytoplasmic autoantibodies (ANCAs)-associated vasculitides (AAV) in the northern Han Chinese population. METHODS: The TLR2 SNPs rs1898830, rs11938228, rs3804099, rs3804100, and rs7656411 were analyzed in 195 AAV patients [granulomatosis with polyangiitis (GPA), n = 100; microscopic polyangiitis (MPA), n = 76; eosinophilic granulomatosis with polyangiitis (EGPA), n = 19] and 501 ethnically and geographically matched healthy controls. Genetic association analysis was carried out using PLINK (version 1.07). For multiple comparisons, a Bonferroni adjustment was conducted (pc = p*n, where n was the number of tested SNPs). RESULTS: The overall frequencies of alleles and genotypes of TLR2 polymorphisms did not differ significantly between AAV patients and controls. The C allele of rs3804100 and the haplotype (C-C) formed by rs3804100 and rs3804099, however, were over-represented in the MPA patient group (pc = 0.018, pc = 0.016, respectively). Moreover, the frequencies of the C allele of both rs3804100 and rs3804099 were higher in the anti-MPO ANCA positive subgroup vs. healthy controls (pc = 0.003, pc = 0.013, respectively). CONCLUSIONS: We conclude that rs3804100 of TLR2 predisposes to MPA in northern Han Chinese. Future studies with larger sample sizes in the northern Han Chinese and other populations are required to extend and verify our current findings.

[Expression of SSA antigen epitopes in minor salivary glands from patients with primary Sjögren's syndrome].

OBJECTIVE: To investigate the correlation between the differential expression of 60 000 SSA epitopes in minor salivary glands (MSG) from patients with primary Sjögren's syndrome (pSS) and glandular inflammation. METHODS: The screening and soluble expression of single-chain fragment V monoclonal antibodies (Scfv McAb) against SSA antigen epitopes (P1: 480 - 494, P2: 310 - 323 and P3: 230 - 241) were performed by phagemid antibody expression system. The expression of epitopes was detected by immunohistochemical assay (IH) in minor salivary glands from these patients. The correlation between epitopes expression and glandular inflammation was analyzed quantitatively. RESULTS: Immunohistochemical assay of MSG with McAb against P1-P3 epitopes showed that the epithelial cells of glandular tubes and striated duct were stained in membrane and cytoplasm. The expression of P1 epitope was higher than the other two in grading score (chi(2) = 12.94, P < 0.01). And a positive correlation was found between the extent of glandular infiltration and the grade of P1 epitope expression (t = 2.27, P < 0.05) but not with P2 or P3 epitope. CONCLUSION: Aberrant redistribution of intracellular SSA antigen epitopes onto the cell membrane of involved cells may break the immune tolerance and thus induce the production of pathogenic autoantibodies involved in triggering and maintaining the tissue-specific autoimmune response in pSS MSG. A significantly high membranous expression of P1 and a positive correlation between P1 and the inflammation of MSG suggest that P1 may be the dominant determinant of the antigen-driven immune response in pSS.