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- Sabrina, MRNA, et al.
(author)
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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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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 459-460
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Conference paper (other academic/artistic)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.
(author)
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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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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1569-
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Journal article (peer-reviewed)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.
(author)
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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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In: Lupus science & medicine. - : BMJ. - 2053-8790. ; 9:1
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Journal article (peer-reviewed)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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