Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females

Klimenta, Biljana; Nefic, Hilada; Prodanović, Nenad; Jadrić, Radivoj; Hukic, Fatima

doi:10.1007/s00296-019-04429-y

Cited by 26 publications

(19 citation statements)

References 23 publications

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“…Accumulating studies have revealed that HLA-DRB1 is closely associated with RA. A previous study from Biljana et al demonstrated the presence of HLA-DRB1 gene-speci c variation possibly contribute to the increased risk of RA [30].…”

Section: Discussionmentioning

confidence: 97%

Identification of Potential Biomarkers in Synovial Tissue of Rheumatoid Arthritis via Integrated Microarray Analysis. Identification of Biomarkers of Rheumatoid Arthritis

Xiong

2021

Preprint

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Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis and subsequent destruction of cartilage and bone. This study aimed to explore RA-related gene markers and the underlying molecular mechanism.Material and Methods: The expression profiles of GSE77298, GSE55235 and GSE12021 were obtained from the Gene Expression Omnibus database. Then, the differential gene expression analysis was conducted between GSE77298 and GSE55235 datasets. Limma package and a Venn diagram were utilized to screen the overlapping differentially expressed genes (DEGs), and Functional enrichment and pathway analysis were performed by using DAVID database. Subsequently, a protein-protein interaction (PPI) network was established, and candidate hub genes were recognized by using STRING and Cytoscape software. Finally, another dataset (GSE12021) was used for the validation of diagnostic value of the candidate hub genes and to identify real hub genes by using receiver operating characteristic (ROC) curves.Results: A total of 385 DEGs were detected, which include 19 downregulated genes and 366 upregulated genes. GO and KEGG pathway analysis showed that DEGs was mainly enriched in various immune and inflammatory response-related functions and pathways. The PPI network was composed of 374 nodes and 767 edges. A total of 8 real hub genes (HLA-DRA, HLA-DRB1, LCK, VAV1, HLA-DPA1, HLA-DPB1, C3AR1 and CD3D) which displayed an excellent diagnostic value for RA were identified.Conclusion: these findings may provide novel and reliable biomarkers for RA, which have some interesting implications for early diagnosis, prognosis and targeted therapy.

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Section: Discussionmentioning

confidence: 97%

Identification of Potential Biomarkers in Synovial Tissue of Rheumatoid Arthritis via Integrated Microarray Analysis. Identification of Biomarkers of Rheumatoid Arthritis

Xiong

2021

Preprint

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“…Platelets adhere and aggregate around bacteria, typically utilizing their GP2b/3a, FcγRIIa, and IgG receptors in conjunction with fibrinogen or fibronectin (34). Various researchers have further documented significant correlations between HLA-DRB and CRP in patients with rheumatoid arthritis, and these genes are even involved in the immune process of myocarditis (35,36). In this study, we established a STEMI rat model in vivo, and assessed the expression patterns of the AMIrelated genes FCGR2B and HLA-DRB4 in the SAI pathway using RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Study on the interaction mechanism between C-reactive protein and platelets in the development of acute myocardial infarction

et al. 2021

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Background: Myocardial infarction (MI) is the single most critical event in coronary disease. Platelets are involved in the processes of acute MI (AMI). They lack nuclear DNA but retain megakaryocyte mRNAs, hence, their transcriptome could provide information preceding coronary events. However, their mechanisms are not clear. In this study, we obtained a gene expression atlas of platelets from patients after their very first AMI, and our purpose was to clarify the mechanisms of platelet involvement in the occurrence of AMI through bioinformatics analyses and animal models of AMI in vivo.Methods: We obtained a gene expression atlas of platelets from patients after their very first AMI from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were retrieved using R language.Weighted gene co-expression network analysis (WGCNA) was implemented in order to construct a gene coexpression correlation network among DEGs. Animal models of AMI in vivo were constructed to confirm the results of the bioinformatics analysis.Results: Gene integration analysis yielded 2,852 DEGs (P<0.05, |log2FC| >1). Bioinformatics analysis demonstrated a significant association between C-reactive protein (CRP) and Staphylococcus aureus infection (SAI) (P=0.015). Data from in vivo experiments showed that CRP increased significantly in AMI rats (P<0.001), and the expression of FCGR2B mRNA and HLA-DRB4 mRNA was elevated in response to the increase of CRP (P<0.001). Conclusions:From the results of this study, we speculate that in the development of AMI, the increase in CRP activates platelets and induces platelets to play an anti-inflammatory role.

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“…When regarding, direct association between RA with IL-6, CRP, sIL-6R, IL-1RA and cellular phosphorylation at Jak/STAT pathway: no association is described with IL-6 levels; a positive association is retrieved with CRP (OR = 1.02; CI95: 1.01–1.03); a lower plasma level of sIL6R is protective for RA (OR = 0.95; CI95: 0.93–0.98) and informative for tocilizumab response [ 21 , [87] , [88] , [89] ]; a higher level of IL-1RA protects from RA (OR = 0.97; IC95: 0.95–0.99) [ 86 ]; and association exists with a negative regulator of the Jak/STAT pathway: SH2B adapter protein 3 (SH2B3) also known as lymphocyte adapter protein (LNK), which is highly express in FLS [ 20 ]. Regarding the association between RA and CRP, discordances are retrieved in the literature and related to the inclusion or not of the HLA locus as instrumental variable (Kawai et al, 2020a) [ 19 , 22 , [90] , [91] , [92] ]. Such assertion is further supported by the observation that the valine 11 at HLA-DRB1 represents the strongest genetic factor able to control CRP level and disease activity at swollen levels (not in tender) in a case report study [ 92 ].…”

Section: Il6/crp/sil6r/il1ra Pathway To Drive Chronic Inflammationmentioning

confidence: 99%

Causal risk and protective factors in rheumatoid arthritis: A genetic update

Arleevskaya

Takha

Petrov

et al. 2021

Journal of Translational Autoimmunity

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The characterization of risk and protective factors in complex diseases such as rheumatoid arthritis (RA) has evolved from epidemiological studies, which test association, to the use of Mendelian randomization approaches, which test direct relationships. Indeed, direct associations with the mucosal origin of RA are retrieved with periodontal disease ( Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans predominantly), interstitial lung involvement, tobacco smoking and air pollutants. Next, factors directly associated with an acquired immune response include genetic factors (HLA DRB1, PTPN22), capacity to produce anti-modified protein antibodies (AMPA), and relatives with a history of autoimmune diseases. Finally, factors can be also classified according to their direct capacity to interfere with the IL-6/CRP/sIL-IL6R proinflammatory pathway as risk factor (body fat, cardiometabolic factors, type 2 diabetes, depressive syndrome) or either as protective factors by controlling of sIL-6R levels (higher education level, and intelligence). Although some co-founders have been characterized (e.g. vitamin D, physical activity, cancer) the direct association with sex-discrepancy, pregnancy, and infections among other factors remains to be better explored.

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Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females

Cited by 26 publications

References 23 publications

Identification of Potential Biomarkers in Synovial Tissue of Rheumatoid Arthritis via Integrated Microarray Analysis. Identification of Biomarkers of Rheumatoid Arthritis

Identification of Potential Biomarkers in Synovial Tissue of Rheumatoid Arthritis via Integrated Microarray Analysis. Identification of Biomarkers of Rheumatoid Arthritis

Study on the interaction mechanism between C-reactive protein and platelets in the development of acute myocardial infarction

Causal risk and protective factors in rheumatoid arthritis: A genetic update

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