المؤلفون: Xu-jie Zhou, Yuta Kochi, Guru P. Maiti, Joel M. Guthridge, Sang Cheol Bae, Mehdi Fazel-Najafabadi, Kek Heng Chua, Judith A. James, Loren L. Looger, Yukinori Okada, Swapan K. Nath, Chikashi Terao, Bhupinder Singh, Celi Sun, Hong Zhang, Matthew T. Weirauch, John B. Harley, Gaurav K. Varshney

المصدر: Arthritis & rheumatology (Hoboken, N.J.), vol 73, iss 12
Arthritis Rheumatol

مصطلحات موضوعية: 1.1 Normal biological development and functioning, Immunology, Lupus, Apoptosis, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Autoimmune Disease, Article, Promoter Regions, Genetic, Rheumatology, Underpinning research, Genetics, Lupus Erythematosus, Systemic, Humans, 2.1 Biological and endogenous factors, Immunology and Allergy, Genetic Predisposition to Disease, Epigenetics, Polymorphism, Aetiology, Promoter Regions, Genetic, Enhancer, Transcription factor, Alleles, Cell Proliferation, Lupus Erythematosus, Inflammatory and immune system, Systemic, Human Genome, Computational Biology, Promoter, Single Nucleotide, Chromatin, CTCF, H3K4me3, Generic health relevance, Cyclin-Dependent Kinase Inhibitor p27, Genome-Wide Association Study, Biotechnology

الوصف: ObjectiveIn a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.MethodsWe performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.ResultsWe replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.ConclusionCollectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad6c0b312b9c3b0c53b18637983f0941Test
https://doi.org/10.1002/art.41799Test

المؤلفون: Suxia Wang, Ping Hou, Ming-Hui Zhao, Fa-juan Cheng, Li Yang, Jennifer Martinez, Ya-li Ren, Xu-jie Zhou, Hong Zhang, Yuan-yuan Qi

المصدر: Annals of the Rheumatic Diseases. 77:1799-1809

مصطلحات موضوعية: 0301 basic medicine, Mice, Inbred MRL lpr, Immunology, Lupus nephritis, mTORC1, Article, General Biochemistry, Genetics and Molecular Biology, Podocyte, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, Autophagy, medicine, Animals, Humans, Immunology and Allergy, skin and connective tissue diseases, Autoantibodies, 030203 arthritis & rheumatology, Kidney, Systemic lupus erythematosus, biology, Podocytes, business.industry, Interferon-alpha, medicine.disease, Lupus Nephritis, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Cancer research, Podocin, biology.protein, Female, business

الوصف: ObjectiveMore recent studies suggested that defects in autophagy contribute to the pathogenesis of SLE, especially in adaptive immunity. Occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for an establishment on the role of autophagy in pathogenesis of LN and as a therapy target.MethodsSystemic and organ-specific aetiologies of autophagy were first evaluated by autophagy protein quantification in tissue homogenates in MRLlpr/lprlupus prone and female C57BL mice. Analysis of gene expression was also adopted in human blood and urine sediments. Then, some key mediators of the disease, including complement inactivated serum, IgG from patients with LN (IgG-LN) and interferon (IFN)-α were chosen to induce podocyte autophagy. Podocyte injuries including apoptosis, podocin derangement, albumin filtration and wound healing were monitored simultaneously with autophagy steady-state and flux.ResultsElevated LC3B in kidney homogenates and increased autophagosomes in podocyte from MRLlpr/lprwere observed. In humans, mRNA levels of some key autophagy genes were increased in blood and urinary sediments, and podocyte autophagosomes were observed in renal biopsies from patients with LN. Complement inactivated serum, IgG-LN and IFN-α could induce podocyte autophagy in a time-dependent and dosage-dependent manner, and by reactive oxygen species production and mTORC1 inhibition, respectively. Autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury.ConclusionPodocyte autophagy is activated in lupus-prone mice and patients with lupus nephritis. Increased autophagy is cytoprotective against antibody and interferon-α induced podocyte injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3902f68f6c3ac72a5021826279b55676Test
https://doi.org/10.1136/annrheumdis-2018-213028Test

المؤلفون: Hong Zhang, Ming-Hui Zhao, Yan Zhang, Yuan-yuan Qi, Fa-juan Cheng, Nan Shen, Wanling Yang, Hai-zhen Yang, Xu-jie Zhou, Swapan K. Nath, Jianyang Ma

المصدر: Arthritis & Rheumatology. 66:2842-2848

مصطلحات موضوعية: business.industry, Genetic heterogeneity, Immunology, Lupus nephritis, Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, medicine.disease, Nephropathy, Rheumatology, Genetic predisposition, Immunology and Allergy, Medicine, skin and connective tissue diseases, business, Nephritis

الوصف: Objective Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome-wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis. Methods In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results In addition to associations with HLA gene polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19–2.19], P = 2.07 × 10−3) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, P = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower MTMR3 transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients. Conclusion Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0c258ca81131f65b6ec651b1819697ceTest
https://doi.org/10.1002/art.38749Test

المؤلفون: Rong Mu, Zhanguo Li, Xu-jie Zhou, Yue-miao Zhang, Chun Li, Swapan K. Nath, Yuan-yuan Qi, Hong Zhang, Ming-Hui Zhao

المصدر: Arthritis & Rheumatology. 67:3091-3093

مصطلحات موضوعية: Rheumatology, business.industry, Association (object-oriented programming), Immunology, Lupus nephritis, medicine, Immunology and Allergy, C-C chemokine receptor type 6, medicine.disease, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0a2e441c03903b73eff163afea658ed4Test
https://doi.org/10.1002/art.39268Test

المؤلفون: Yi Zhang, H Zhang, Fa-juan Cheng, Ping Hou, Yuan-yuan Qi, Xu-jie Zhou, M.-H. Zhao

مصطلحات موضوعية: 0301 basic medicine, Untranslated region, Adult, Male, Immunology, Lupus nephritis, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Severity of Illness Index, 03 medical and health sciences, Ikaros Transcription Factor, 0302 clinical medicine, Rheumatology, Asian People, Polymorphism (computer science), medicine, Odds Ratio, Immunology and Allergy, SNP, Humans, Genetic Predisposition to Disease, Genetic association, 030203 arthritis & rheumatology, Genetics, General Medicine, Middle Aged, Protective Factors, medicine.disease, Phenotype, Lupus Nephritis, 030104 developmental biology, Logistic Models, Case-Control Studies, Expression quantitative trait loci, Female, 5' Untranslated Regions

الوصف: Objectives: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. Method: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. Results: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 × 10−3 and p = 3.00 × 10−2) and reinforced in combination (p = 1.36 × 10−3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. Conclusions: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fafc1b60284d5743e773295b8305ebcfTest

المؤلفون: Jicheng Lv, Xiaolan Lu, Swapan K. Nath, Nan Shen, Xu-jie Zhou, Zhanguo Li, Yin Su, Hai-zhen Yang, Sai-Nan Zhu, Lian-xiang Qin, Hong Zhang, Ming-Hui Zhao

المصدر: Arthritis & Rheumatism. 64:222-231

مصطلحات موضوعية: Adult, Male, Genotype, Immunology, OX40 Ligand, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, TNFAIP3, Article, Asian People, Rheumatology, Gene interaction, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Genetic Predisposition to Disease, Pharmacology (medical), skin and connective tissue diseases, Tumor Necrosis Factor alpha-Induced Protein 3, B cell, Genetic association, Genetics, Lupus erythematosus, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Epistasis, Genetic, medicine.disease, TNF Receptor-Associated Factor 1, Proto-Oncogene Proteins c-rel, DNA-Binding Proteins, src-Family Kinases, medicine.anatomical_structure, Female, Genome-Wide Association Study, Signal Transduction

الوصف: Although the number of convincingly established genetic associations with systemic lupus erythematosus (SLE) has increased sharply over the last few years, refinement of these associations is required, and their potential roles in gene-gene interactions need to be further investigated. Recent genome-wide association studies (GWAS) in SLE have produced renewed interest in B cell/T cell responses and the NF-κB signaling pathway. The aim of this study was to search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs), in using an approach based on the role of signaling pathways.The SNPs in BLK, TNFSF4, TRAF1, TNFAIP3, and REL were replicated in order to evaluate genetic associations with SLE. TaqMan genotyping was conducted in 804 Chinese patients with SLE and 722 matched control subjects. A multiple logistic regression model was used to estimate the multiplicative interaction effect of the SNPs, and additive interactions were analyzed by 2×2 factorial designs. Data from a previously published GWAS conducted by the International Consortium on the Genetics of Systemic Lupus Erythematosus were derived for comparison and validation.Single-marker analysis validated the association of BLK rs2736340 (P=4.25×10(-6)) as well as TNFSF4 rs2205960 (P=2.82×10(-5)) and TNFAIP3 rs5029939 (P=1.92×10(-3)) with SLE susceptibility in Chinese. Multiplicative interaction analysis indicated that BLK had an interactive effect with TNFSF4 in Chinese patients with SLE (P=6.57×10(-4)). Additive interaction analysis revealed interactions between TRAF1 and TNFAIP3 in both Chinese (P=2.18×10(-3)) and Caucasians (P=2.86×10(-4)). In addition, multiple tendencies toward interactions were observed, and an additive effect was observed as the number of risk genotypes increased.The results of this study provide evidence of the possible gene-gene interactions of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in SLE, which may represent a synergic effect of T cells and B cells through the NF-κB pathway in determining immunologic aberration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1794d473049ae361aa84875d93d81f8aTest
https://doi.org/10.1002/art.33318Test

المؤلفون: Xia Liu, Zhanguo Li, Hong Zhang, Xu Liu, Ru Li, Ping Zhu, Jing He, Xinyu Wu, Yi Zhao, Baoli Zhu, Xu-jie Zhou, Xiaolan Lu, Xiangyuan Liu, Jianhua Xu, Jianping Guo

المصدر: Annals of the Rheumatic Diseases. 70:1648-1651

مصطلحات موضوعية: Adult, Male, China, Linkage disequilibrium, Immunology, Single-nucleotide polymorphism, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Linkage Disequilibrium, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, Young Adult, Chinese han population, Asian People, Gene Frequency, Rheumatology, Cornified Envelope Proline-Rich Proteins, Psoriasis, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Genetic Predisposition to Disease, In patient, Allele, Aged, business.industry, Middle Aged, medicine.disease, Connective tissue disease, Case-Control Studies, Rheumatoid arthritis, Female, business, Gene Deletion

الوصف: Objectives The deletion of LCE3C_LCE3B confers susceptibility to psoriasis and rheumatoid arthritis (RA) in Caucasians. The aim of this study was to investigate the variant involvement in RA in the Chinese Han population and to further explore its potential role in the susceptibility to systemic lupus erythematosus (SLE). Methods LCE3C_LCE3B - del was genotyped in 898 patients with RA and 681 healthy controls. Two single nucleotide polymorphisms (SNPs, rs4112788 and rs4085613) in strong linkage disequilibrium with LCE3C_LCE3B - del were then genotyped in patients with RA (n=1222), SLE (n=870) and healthy controls (n=1031). Results The deletion of LCE3C_LCE3B and SNPs rs4112788 and rs4085613 showed an association with RA (allele analysis: p=7.72×10 −4 , OR 1.28, 95% CI 1.11 to 1.47; p=6.39×10 −4 , OR 1.23, 95% CI 1.09 to 1.38; and p=5.38×10 −4 , OR 1.23, 95% CI 1.10 to 1.39, respectively). The two SNPs were also significantly associated with SLE (allele analysis: p=7.68×10 −3 , OR 1.19, 95% CI 1.05 to 1.36 and p=5.30×10 −3 , OR 1.20, 95% CI 1.06 to 1.37). Conclusions This study provides evidence for an association between LCE3C_LCE3B - del and RA in non-Caucasian populations, and SNPs rs4112788 and rs4085613 tagging LCE3C_LCE3B - del were novel susceptibility factors for SLE.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef567001a0c7933e204a54c4c732036fTest
https://doi.org/10.1136/ard.2010.148072Test

المؤلفون: Zhanguo Li, Xiaolan Lu, Ming-Hui Zhao, Jicheng Lv, Lian-xiang Qin, Hai-zhen Yang, Yin Su, Xu-jie Zhou, Hong Zhang

المصدر: Annals of the Rheumatic Diseases. 70:1330-1337

مصطلحات موضوعية: Adult, Male, Candidate gene, Genotype, T-Lymphocytes, Immunology, Locus (genetics), Single-nucleotide polymorphism, Biology, Lymphocyte Activation, Polymorphism, Single Nucleotide, Linkage Disequilibrium, General Biochemistry, Genetics and Molecular Biology, Autophagy-Related Protein 5, Young Adult, Asian People, Rheumatology, PRDM1, Autophagy, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Genetic Predisposition to Disease, RNA, Messenger, Gene, Genotyping, Cells, Cultured, Genetic association, Genetics, B-Lymphocytes, Middle Aged, Repressor Proteins, Gene Expression Regulation, Case-Control Studies, IRGM, Female, Positive Regulatory Domain I-Binding Factor 1, Microtubule-Associated Proteins

الوصف: Objective Recent genome-wide association studies suggested the PRDM1-ATG5 gene region as a systemic lupus erythematosus (SLE)-associated locus both in Caucasian and Chinese populations; however, the candidate gene was still obscure and the possible functional significance needed to be determined. Methods In this study, by a multistage integrative strategy, the authors first performed a case–control association study involving 1745 individuals in the Chinese population by genotyping nine single nucleotide polymorphisms within this region, and a meta-analysis was conducted. Correlation between associated genotypes and expression levels of messenger RNA in B-cell lines from 210 unrelated HapMap data was examined, and was validated in vitro. To determine the biological significance, a genetic association study was also checked in a pathway-based manner and the significant associations were validated in a second 844 Chinese cohort. Results A peak of association was found in the intergenic region (p=0.036–3.26×10 −4 ). Meta-analysis consolidated the association between rs548234 and SLE (OR 1.254, p=1.28×10 −16 ). Significant positive correlations with ATG5 expression were identified, suggesting ATG5 as a candidate gene in the region. Epstein–Barr virus B-cell-based downstream gene expression analysis supported a functional effect of rs548234 and rs6937876, and in-vitro experiments confirmed the regulatory effect of rs6937876 in B-cell populations. Finally, an autophagy pathway-based genetic association study identified ATG7 (p=1.12×10 −4 ) and IRGM (p=0.015) as novel candidate genes, and gene–gene interactions were observed between ATG5 , ATG7 and IRGM . Conclusion These data may demonstrate that autophagy is involved in the pathogenesis of SLE and imply a common biological pathway in autoimmunity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d0b935f1c1635ddb3ed15c4b8361db1Test
https://doi.org/10.1136/ard.2010.140111Test

المؤلفون: Fa-Juan Cheng, Hong Zhang, Xu-jie Zhou, Yuan-yuan Qi

المصدر: The Journal of rheumatology. 40(10)

مصطلحات موضوعية: Male, Immunology, Disease, Rheumatology, Asian People, Missing heritability problem, Immunology and Allergy, Medicine, Humans, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, B cell, Genetic Association Studies, Adaptor Proteins, Signal Transducing, Genetics, Autoimmune disease, Systemic lupus erythematosus, business.industry, Genetic heterogeneity, Membrane Proteins, Epistasis, Genetic, medicine.disease, White (mutation), medicine.anatomical_structure, src-Family Kinases, Epistasis, Female, business

الوصف: To the Editor: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic components, with over 40 susceptibility loci identified at present. These SLE susceptibility loci are predominantly common variants that have been confirmed among multiple ancestries, suggesting shared mechanisms in disease etiology1. However, genetic heterogeneity was also suggested, as some genetic polymorphisms are restricted to specific ethnic populations. Recent descriptions of gene–gene interactions, or epistasis, may explain some of the genetic heterogeneity and missing heritability in SLE. We previously reported potential epistasis between BLK and TNFSF4 in both Chinese and white populations, suggesting that unbalanced functions of B cell and T cell signaling may be involved synergistically in the pathogenesis of SLE2. Another large-scale association study confirmed the genetic interactions between BANK1 and BLK in Europeans, indicating B cell activity and a B cell-specific pathway were crucial in lupus pathogenesis3. No further replications were conducted in Chinese subjects or other populations with independent sets of cases … Address correspondence to Prof. H. Zhang, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China. E-mail: hongzh{at}bjmu.edu.cn

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a79e4e2b4ad8101d0f267487113dfb57Test
https://pubmed.ncbi.nlm.nih.gov/24085759Test

المؤلفون: Hong Zhang, Ming-Hui Zhao, Ji-Cheng Lv, Xu-jie Zhou

المصدر: The Journal of Rheumatology. 37:1359-1360

مصطلحات موضوعية: Chinese han population, Immune system, Rheumatology, business.industry, Immunology, Lupus nephritis, medicine, Etiology, Immunology and Allergy, medicine.disease, business, Gene

الوصف: To the Editor: Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) and is an important predictor of poor outcome1. Susceptibility to LN is the end result of complex interactions between polymorphic genetic factors involved in the regulation of immune responses. However, to date, a clear etiology is still obscure. Recently, it was reported that kallikrein genes, especially KLK1 gene, were associated with LN in mice and in Caucasians. However, such an association was not shown in all the investigated populations2,3. This implies that different genetic influences exist in different ethnic groups2–5, and it was decided to further validate the association of KLK1 gene polymorphisms with LN in a Chinese Han population. A case-control association study was performed on 306 LN patients (age 32.2 ± 11.1 yrs, 84.2% female) and 338 matched healthy controls (age 31.7 ± 9.1 yrs, 55.8% female). …

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::70f615db4f326b3e2edced482ed8dad5Test
https://doi.org/10.3899/jrheum.091316Test