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- Sabrina, MRNA, et al.
(författare)
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CHANGES OF RF ISOTYPE PROFILE IN PATIENTS WITH RHEUSMATOID ARTHRITIS: DATA FROM 10 YEARS FOLLOW-UP STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 459-460
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Presence of autoantibodies such as anti-cyclic citrullinated peptide (anti-CCP2) and rheumatoid factor (RF) is of considerable diagnostic and prognostic value in patients with rheumatoid arthritis (RA). Limited data are available for autoantibody profile changes over time in patients with RA.Objectives:Thus, we compared the presence of anti-CCP2 and different RF isotypes in individual RA patients at baseline and during 10 years follow-up.Methods:A total of 320 RA patients from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study was included in this study. The presence of anti-CCP2, IgM RF, IgG RF, and IgA RF at baseline and at later time point (±10 years) were determined using enzyme-linked immunosorbent assays, with identical techniques in paired samples. Seropositive RA is defined by the presence of at least one autoantibody, whilst seronegative RA is defined by the absence of all investigated autoantibodies.Results:The proportion of seropositive RA were higher for the follow-up samples (n=263, 82.2%) as compared to the baseline samples (n=251, 78.4%). Among the baseline samples, 105 (41.8%) were positive for anti-CCP2 and all RF isotypes. Of these individuals, 85 (81.0%) remained positive for all antibodies at the follow-up, while 20 (19.0%) lost one or more RF isotypes (4 IgM RF, 19 IgG RF and 13 IgA RF). Interestingly, 14 (5.6%) RA patients who were seropositive at baseline became totally seronegative after follow-up. Among the 69 patients seronegative at baseline, 26 (37.7%) acquired one or more autoantibodies at follow-up (14 IgM RF, 2 IgG RF, 9 IgA RF and 8 anti-CCP2) (Figure 1).Conclusion:Anti-CCP2 present at baseline usually remained at follow-up. Among Malaysian RA patients, changes in status were mainly found for RF of all isotypes.References:[1]Barra, Lillian et al. “Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated peptide in patients with early inflammatory arthritis: a systematic literature review.” Rheumatology (Oxford, England) vol. 50,2 (2011): 311-6.[2]van Delft, Myrthe A M, and Tom W J Huizinga. “An overview of autoantibodies in rheumatoid arthritis.” Journal of autoimmunity vol. 110 (2020): 102392.Figure 1.Comparison of serum autoantibody profile in rheumatoid arthritis patients during baseline enrolment and 10 years follow-up.Acknowledgements:The authors would like to thank the Director General of Health, Ministry of Health Malaysia for supporting this study. The authors are also indebted to participants for their kind participation. This study was financially supported by the Ministry of Health, Malaysia (JPP-IMR 08-012; 18-051).Disclosure of Interests:None declared
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- Sakaue, S, et al.
(författare)
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Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1569-
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Tidskriftsartikel (refereegranskat)abstract
- The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t-SNE, PCA-t-SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population (n = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS.
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- Selvaraja, M, et al.
(författare)
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Human leucocyte antigens profiling in Malay female patients with systemic lupus erythematosus: are we the same or different?
- 2022
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Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- SLE is a heterogeneous autoimmune disease, in terms of clinical presentation, incidence and severity across diverse ethnic populations. We investigated the human leucocyte antigens (HLA) profile (ie, HLA-A, HLA-B and HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1) in Malaysian Malay female patients with SLE and determined the generalisability of the published HLA risk factors across different ethnic populations globally including Malaysia.MethodsOne hundred Malay female patients with SLE were recruited between January 2016 and October 2017 from a nephrology clinic. All patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 alleles using PCR sequence-specific oligonucleotides method on Luminex platform. A total of 951 HLA genotyped population-based Malay control subjects was used for association testing by means of OR with 95% CIs.ResultsOur findings convincingly validated common associations between HLA−A*11 (OR=1.65, p=3.36×10−3, corrected P (Pc)=4.03×10−2) and DQB1*05:01 (OR=1.56, p=2.02×10−2, Pc=non−significant) and SLE susceptibility in the Malay population. In contrast, DQB1*03:01 (OR=0.51, p=4.06×10−4, Pc=6.50×10−3) were associated with decreased risk of SLE in Malay population. Additionally, we also detected novel associations of susceptibility HLA genes (ie, HLA-B*38:02, DPA1*02:02, DPB1*14:01) and protective HLA genes (ie, DPA1*01:03). When comparing the current data with data from previously published studies from Caucasian, African and Asian populations, DRB1*15 alleles, DQB1*03:01 and DQA1*01:02 were corroborated as universal susceptibility and protective genes.ConclusionsThis study reveals multiple HLA alleles associated with susceptibility and protection against risk of developing SLE in Malay female population with renal disorders. In addition, the published data from different ethnic populations together with our study further support the notion that the genetic effects from association with DRB1*15:01/02, DQB1*03:01 and DQA1*01:02 alleles are generalised to multiple ethnic populations of Caucasian, African and Asian descents.
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- Tan, LK, et al.
(författare)
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EXPOSURE TO DENGUE INFECTION DO NOT RAISE RISK OF RHEUMATOID ARTHRITIS: FINDINGS FROM THE MALAYSIAN EPIDEMIOLOGICAL INVESTIGATION OF RHEUMATOID ARTHRITIS (MYEIRA) CASE-CONTROL STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 53-53
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Dengue infection is associated with joints pain mimicking disease onset symptom of rheumatoid arthritis (RA). However, there is lack of epidemiological studies on exposure to dengue infection and risk of future RA.Objectives:We investigated the relationship between exposure to dengue infection and risk of developing different subsets of RA, defined by the presence of anti-citrullinated peptide antibody (ACPA) in the multi-ethnic Malaysian population.Methods:Serum samples from 1,235 RA cases (i.e. 516 Malay, 254 Chinese, 405 Indians and 60 others/mixed-ethnicity) and 1,624 epidemiological matched population-based controls (i.e. 1,023 Malay, 208 Chinese, 297 Indians and 96 others/mixed-ethnicity) were assayed for presence of dengue IgG antibody using World Health Organization recommended ELISA kits. Positive results of dengue IgG antibodies indicates previous exposure to dengue infection(s). We performed chi-square and Mann-Whitney U analysis to determine the association of ever-exposed dengue infection with ACPA-positive/ACPA-negative RA and to investigate the antibody frequency and levels among the studied populations.Results:We observed high occurrence of dengue IgG antibody in the overall RA cases (79.7%) and matched controls (77.3%), with no significant differences detected between the ACPA subsets of RA. Ethnicity stratification analysis revealed a decrease risk of developing ACPA-positive RA in the Indian patients with positive dengue IgG antibody (OR=0.59, 95% CI=0.37-0.94, p=0.03), and in particular patients with elevated level of dengue IgG antibody (OR=0.44, 95% CI=0.25-0.78, p<0.05). On the other hand, the significant decrease mean levels of dengue IgG antibody were observed in the ACPA-positive RA subset for all three major ethnic groups (i.e. Malay, p<0.0001, Chinese, p<0.01 and Indian<0.05) (Figure 1). No association was observed between presence of dengue IgG antibody and ACPA-negative RA subset.Figure 1.Comparison of mean dengue IgG antibody level between ever-exposed dengue infection RA cases, stratified by ACPA status. Comparison of median dengue IgG antibody level between the ever-exposed dengue infection ACPA-positive RA and normal controls in the four ethnic groups. The red line indicates the mean level of dengue IgG antibody levelConclusion:Our findings demonstrated that exposure to dengue infection do not increase the risk of developing future RA in the multi-ethnic Malaysian population. The inverse associations observed in the Indian ethnic group are in line with the other studies investigating exposure to viral infection and risk of RA.References:[1]Sherina et al (2017) Low levels of antibodies against common viruses associate with anti-citrullinated protein antibody-positive rheumatoid arthritis; implications for disease aetiology. Arthritis Research & Therapy 2017, 19:2169[2]Gissel García et. al. (2011) Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders. International Journal of Infectious Diseases 15 (2011) e38–e43Acknowledgements:The authors would like to thank the Director General of Health, Ministry of Health Malaysia for supporting this study. The authors are also indebted to participants for their kind participation. This study was financially supported by the Ministry of Health, Malaysia (JPP-IMR 17-025) and the short-term research grant by UniKL RCMP (str16037).Disclosure of Interests:None declared
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- Too, CL, et al.
(författare)
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Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study
- 2016
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 75:6, s. 997-1002
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Tidskriftsartikel (refereegranskat)abstract
- Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.MethodsData from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case–control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.ResultsOccupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).ConclusionsThis is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene–environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.
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