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  1. Nanomaterials for Nanotheranostics: Tuning Their Properties According to Disease Needs
    Wong XY, Sena-Torralba A, Álvarez-Diduk R, Muthoosamy K, Merkoçi A
    ACS Nano, 2020 03 24;14(3):2585-2627.
    PMID: 32031781 DOI: 10.1021/acsnano.9b08133
    Nanotheranostics is one of the biggest scientific breakthroughs in nanomedicine. Most of the currently available diagnosis and therapies are invasive, time-consuming, and associated with severe toxic side effects. Nanotheranostics, on the other hand, has the potential to bridge this gap by harnessing the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics with markedly enhanced efficacy. However, nanomaterial applications in nanotheranostics are still in its infancy. This is due to the fact that each disease has a particular microenvironment with well-defined characteristics, which promotes deeper selection criteria of nanomaterials to meet the disease needs. In this review, we have outlined how nanomaterials are designed and tailored for nanotheranostics of cancer and other diseases such as neurodegenerative, autoimmune (particularly on rheumatoid arthritis), and cardiovascular diseases. The penetrability and retention of a nanomaterial in the biological system, the therapeutic strategy used, and the imaging mode selected are some of the aspects discussed for each disease. The specific properties of the nanomaterials in terms of feasibility, physicochemical challenges, progress in clinical trials, its toxicity, and their future application on translational medicine are addressed. Our review meticulously and critically examines the applications of nanotheranostics with various nanomaterials, including graphene, across several diseases, offering a broader perspective of this emerging field.
    Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*
  2. The relationship between soluble CD30 (sCD30) and rheumatoid arthritis (RA) patients. [Abstract]
    Hee CS, Gun SC, Naidu R, Das Gupta E, Somnath SD, Radhakrishnan A
    APLAR Journal of Rheumatology, 2006;9.
    Matched MeSH terms: Arthritis, Rheumatoid
  3. Rheumatoid arthritis: case review from MOH collaborative rheumatology centers in Malaysia. [Abstract]
    Sulaiman W, Othman M, Mokhtar AM, Rosman A, Ong SG, Soo IS, et al.
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A54-A55.
    DOI: 10.1111/j.1479-8077.2006.00199_24.x
    Objective: To determine the number of RA cases and to evaluate the demographic patterns in all 4 Rheumatology Referral Centers under the Ministry of Health Malaysia. Materials and methods: One thousand and eighty-four rheumatoid arthritis patients from all 4 centers i.e. Hospital Selayang, Putra Jaya, Seremban and Taiping which are situated in the west coast of West Malaysia, using rheumatoid arthritis database comprising of basic clinical and patient questionnaire, until the end of year 2004 were analysed. Results: At the time of documentation, 88.6% were female at all range of ages especially between age of 25 and 54 years (77.6%) with female to male ratio 8 :1. 52.1% were housewives. Mean age of onset of RA was 49.6 ± 11.8 SD with female 49.3 ± 11.7 SD and male 52.0 ± 12.0 SD (p < 0.05). Indian was the predominant ethnic group (54.5%), followed by Malay (31.4%), Chinese (11.6%) and others (27%). Majority had their education up to secondary level (50.8%), followed by primary (32.6%), and tertiary (6.3%) levels while 10.3% of cases had not received any formal education in their lives. 74.4% were seropositive and 87.3% fulfilled at least 4 out of 7 American College of Rheumatology (ACR) revised criteria for rheumatoid arthritis. 74% were diagnosed RA within 2 years after the onset of arthritis. Seropositivity was not significantly related to gender. Positive rheumatoid factor was dominated by Indian followed by Malay and Chinese. 83.3% were married. 23.3% female and 33.9% male between age group 25-54 were employed. 7.4% had achieved their retirement at time of entry whilst 8.9% were unemployed. Employment status was statistically significant across gender (p < 0.001). The cases differed between rheumatology centers as well as individual practices. Conclusion: There are increasing numbers of RA cases in Malaysia. Results from this study did not reflect the true prevalence of RA in Malaysia. Hence, a larger and more comprehensive database on RA with collaboration of all Government and Private Hospitals in the whole nation will provide better information about the patient case mix in different healthcare settings, treatment practice as well as disease complications. The implementation of rheumatology centers with better regional cooperation, will lead to better treatment and outcome in terms of identification of early as well as established RA cases. Early referral to the centers will be made possible for proper treatment institution and rehabilitation. Hence, improve quality of life including socio-economic status especially among those within the productive age.
    Matched MeSH terms: Arthritis, Rheumatoid
  4. A review of pulmonary involvement in rheumatoid arthritis
    Arshad A
    APLAR Journal of Rheumatology, 2005;8(1):16-18.
    DOI: 10.1111/j.1479-8077.2005.00116.x
    Pulmonary involvement in rheumatoid arthritis (RA) is a recognized complication but not often well described in the literature and also in major medical textbooks. Thus, for most medical practitioners who look after RA patients, pulmonary complications are often missed and not given much attention. This article will review the current literature of pulmonary involvement in RA and to increase awareness of its existence., Copyright (C) 2005 Blackwell Publishing Ltd
    Matched MeSH terms: Arthritis, Rheumatoid
  5. Mortality in rheumatoid arthritis: time to take it seriously
    Arshad A, Shahid MS
    APLAR Journal of Rheumatology, 2005;8(3):154-158.
    DOI: 10.1111/j.1479-8077.2005.00158.x
    Rheumatoid arthritis (RA) is often regarded as benign and not a serious disease. Yet patients with RA have a substantially reduced life expectancy. Patients with RA are particularly at risk of death from cardiovascular disease, infection and renal disease. A few variables are now recognized as important predictive markers, such as disease duration, severity, sex, educational level and treatment., Copyright (C) 2005 Blackwell Publishing Ltd
    Matched MeSH terms: Arthritis, Rheumatoid
  6. To compare ESR and CRP as predictors of disease activity in rheumatoid arthritis patients in Hospital Seremban. [Abstract]
    Gun SC, Loh YL, Das Gupta E
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A185.
    Background: Rheumatoid arthritis (RA) is an inflammatory disease. Predictors of disease activity include presence of joint inflammation, blood investigations such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). ESR is said to be imprecise as it is affected by aging, female sex, obesity, pregnancy, anaemia and polycythaemia. But it is inexpensive and easy to perform. CRP is produced as an acute phase reactant by the liver in response to interleukin 6 and other cytokines. CRP is more specific but costs more than ESR. Both tests are done in the rheumatology clinic of Hospital Seremban. Objective: To compare the usefulness of ESR and CRP as a predictor of disease activity in rheumatoid arthritis (RA) patients. Method: This was a retrospective study. The medical records of 248 RA patients who attended the rheumatology clinic, Hospital Seremban between 1 January 2004 and 31 Dec 2004 were reviewed. The following data were obtained: joint swelling and tenderness, other clinical features which indicate inflammation secondary to infection or trauma and inflammation of soft tissue, ESR, CRP, FBC and UFEME. Results: Data was analysed and the results showed that a total number of 248 patients were seen. There were 13 defaulters. Of the 248 patients there were 929 patients' visits. Of the total number of patients' visits where patients clinically had active disease, 80.2% had raised ESR while 88.8% had raised CRP. As for visits where patients had quiescent disease clinically, 57.3% had normal ESR and 36.5% had normal CRP. Conclusion: CRP is more sensitive but less specific than ESR. This suggests that we still should use both tests as they complement each other. ESR can serve as a countercheck for CRP and vice versa.
    Matched MeSH terms: Arthritis, Rheumatoid
  7. Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) in Malaysian patients with rheumatoid arthritis. [Abstract]
    Yuslina MY, Shahnaz M, Too CL, Hussein H, Wahinuddin S, Eashwary M, et al.
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A187-A188.
    Background: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) is a new serological test for the diagnosis of rheumatoid arthritis (RA). It is an enzyme immunoassay (EIA) for the detection of antibodies directed toward citrullinated peptides. Studies show this test has an improved diagnostic value compared to rheumatoid factor (RF). Objective: To determine the sensitivity and specificity of anti-CCP in patients with rheumatoid arthritis and other rheumatic diseases. Method: 227 serum samples for rheumatology clinics (Putrajaya, Taiping, and Ipoh Hospital) were tested for the presence of anti-CCP and rheumatoid factor (RF). These included 171 patients diagnosed with RA and 56 from other rheumatic diseases. Patient demographic data, clinical diagnosis, radiographic information and other laboratory data were obtained from the patients' clinical notes. Results: Anti-CCP antibodies were detected in 76.6% (131/171) patients with RA and 17.9% (10/56) patients with other arthritis. The sensitivity and specificity of anti-CCP reactivity at the optimal cut off values were 66.1% and 87.5% respectively. The sensitivity of anti-CCP was higher than that for RF (41.8%). However, the presence of either anti-CCP or RF improved the sensitivity to 76.2%. Conclusion: The detection of anti-CCP alone maybe useful in the diagnosis of RA. However, when used concomitantly with RF, it can improve the diagnostic ability significantly.
    Matched MeSH terms: Arthritis, Rheumatoid
  8. Immunological studies in Malaysian patients with rheumatoid arthritis
    Sivapatham G, Gong NC, Pang T
    ASEAN Journal of Clinical Sciences, 1982;3(4):329-33.
    Twenty-one patients with rheumatoid arthritis (RA) were investigated for various immunological parameters, both humoral and cellular. IgG concentration was 1673+/-266 mg/dl, IgM 259+/-108 mg/dl and IgA 302 +/-7 mg/dl. Enumeration of T lymphocytes in peripheral blood revealed a value of 66% with a B cell count of 10%. Additionally, IgG levels, in 5 selected patients, appeared to fall to normal levels in the course of treatament with D-penicillamine. The significance of these findings are discussed.
    Matched MeSH terms: Arthritis, Rheumatoid
  9. Fulltext Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth
    Yap HY, Siow TS, Chow SK, Teow SY
    Adv Virol, 2019;2019:6464521.
    PMID: 31049064 DOI: 10.1155/2019/6464521
    Epstein-Barr virus (EBV) is one of the common human herpesvirus types in the world. EBV is known to infect more than 95% of adults in the world. The virus mainly infects B lymphocytes and could immortalize and transform the cells into EBV-bearing lymphoblastoid cell lines (LCLs). Limited studies have been focused on characterizing the surface marker expression of the immortalized LCLs. This study demonstrates the generation of 15 LCLs from sixteen rheumatoid arthritis (RA) patients and a healthy volunteer using B95-8 marmoset-derived EBV. The success rate of LCL generation was 88.23%. All CD19+ LCLs expressed CD23 (16.94-58.9%) and CD27 (15.74-80.89%) on cell surface. Our data demonstrated two distinct categories of LCLs (fast- and slow-growing) (p<0.05) based on their doubling time. The slow-growing LCLs showed lower CD23 level (35.28%) compared to fast-growing LCLs (42.39%). In contrast, the slow-growing LCLs showed higher percentage in both CD27 alone and CD23+CD27+ in combination. Overall, these findings may suggest the correlations of cellular CD23 and CD27 expression with the proliferation rate of the generated LCLs. Increase expression of CD23 may play a role in EBV immortalization of B-cells and the growth and maintenance of the EBV-transformed LCLs while CD27 expression might have inhibitory effects on LCL proliferation. Further investigations are warranted to these speculations.

    Study site: Sunway Medical Centre, Malaysia
    Matched MeSH terms: Arthritis, Rheumatoid
  10. Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation
    Sharma JN
    Agents Actions Suppl., 1992;38 ( Pt 3):343-61.
    PMID: 1334358
    Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.
    Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
  11. Fulltext Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study
    Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.
    Ann Rheum Dis, 2016 06;75(6):997-1002.
    PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278
    OBJECTIVES: 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.

    METHODS: Data 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.

    RESULTS: Occupational 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).

    CONCLUSIONS: This 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.
    Matched MeSH terms: Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/genetics
  12. Fulltext Pattern of rheumatoid arthritis in West Malaysia
    Toh BH, Sengupta S, Ang AH, White JC, Lau KS
    Ann Rheum Dis, 1973 Mar;32(2):151-6.
    PMID: 4120913 DOI: 10.1136/ard.32.2.151
    In West Malaysia RA appears to be less common than in temperate climates, but more common than in tropical Africa; furthermore, the incidence of gout and SLE is comparable. The clinical manifestations of RA are milder than those seen in more temperate climates. Subcutaneous rheumatoid nodules have not been observed. Positive serological tests for RF are significantly higher than in the general Malaysian population, but still lower than those reported for patients with RA in temperate climates. Of the three main ethnic groups, the highest incidence of positive results is found in the Chinese.
    Study site: Arthritis Clinic, University Hospital, Kuala Lumpur (University Malaya Medical Centre, UMMC, Kuala Lumpur, Malaysia)
    Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/immunology; Arthritis, Rheumatoid/epidemiology*
  13. Fulltext Medical conditions associated with tooth loss among Saudi adults
    Hamasha, Abed Al-Hadi, Almogbel, Lolowh, Alshehri, Abeer, Alssafia, Fatimah, Alghamdi, Hanan, Alajmia, Alanoud, et al.
    Archives of Orofacial Sciences, 2018;13(1):16-21.
    MyJurnal
    Upon reviewing the literature, the prevalence of many systemic conditions such as diabetes,
    hypertension, asthma and rheumatoid arthritis were reported to be high in Saudi Arabia. The relationship of these
    conditions with tooth loss among Saudi population was not investigated. Therefore, the aim of the present study
    is to explore the relationship between tooth loss and most common medical conditions among Saudi dental
    patient. The study participants were 250 patients who were randomly selected from the College of Dentistry
    database of King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) in Riyadh, Saudi Arabia.
    Participants were requested to answer self-administered questionnaires related to their demographic as well as
    general health questions concerned to the presence of systemic medical conditions. Missing teeth were
    determined after examining the orthopantogram radiographs and reviewing the Romexis and SALUD databases.
    Descriptive statistics, independent t-test and linear multiple regression model were performed using SPSS
    software. The mean number of missing teeth among the study population was 5.8 teeth per person. The mean
    number of missing teeth was higher among subjects with diabetes, hypertension, rheumatoid arthritis,
    cardiovascular diseases, or osteoporosis compared to healthy individuals. A multiple linear regression analysis
    model revealed that diabetes, hypertension and rheumatoid were significant predictors of missing teeth among
    Saudi population. These results highlight the importance of the effect of medical conditions on oral health.
    Matched MeSH terms: Arthritis, Rheumatoid
  14. Fulltext Knowledge of cardiovascular disease risk in rheumatoid arthritis patients before and after educational intervention from a Southeast Asia country: Malaysia
    Teoh BC, Syed Sulaiman SA, Tan BE
    Arch Rheumatol, 2021 Mar;36(1):63-71.
    PMID: 34046570 DOI: 10.46497/ArchRheumatol.2021.7726
    Objectives: This study aims to improve knowledge on cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients using a multi- language leaflet tailored to our multi-ethnic patient population.

    Patients and methods: This was a prospective study conducted in Hospital Pulau Pinang, Malaysia, between March 2015 and June 2015. Educational intervention was provided to 96 patients (11 males, 85 females; mean age 52.4±12.9 years; range, 20 to 83 years) who fulfilled the inclusion/exclusion criteria. Questionnaires to assess knowledge of CVD risk were given to patients to be answered before reading the informative leaflet, after one hour of intervention, and during their next follow-up three months from the intervention. Both the informative leaflet and questionnaires were prepared in English and then translated into Malay and Chinese languages to suit the need of local patients.

    Results: Our results showed that RA patients had good knowledge at baseline regarding risk of smoking, hypertension, and hyperlipidemia on increasing CVD risk and that exercise would not damage their joints. However, they had low knowledge at baseline regarding the amount of exercise needed for lower CVD risks and risk of CVD with use of anti-inflammatory drugs in RA. Total knowledge score increased significantly from baseline immediately after educational intervention. However, total knowledge score decreased after three months compared to immediate post- intervention phase while it was still significantly higher compared to baseline. The improvement was most obvious for knowledge regarding anti- inflammatory drugs and CVD risk and knowledge regarding the number of flares and CVD risk. Our study did not find any significant association between demographic characteristics and traditional cardiovascular risk factors with knowledge of CVD risk.

    Conclusion: Rheumatoid arthritis patients have low knowledge regarding their CVD risk related to their disease. The intervention of providing an informative leaflet effectively improved the knowledge of this group of patients on CVD risk particularly in the field related to RA-specific risk.

    Matched MeSH terms: Arthritis, Rheumatoid
  15. Fulltext Anti-citrullinated cyclic peptide antibody and functional disability are associated with poor sleep quality in rheumatoid arthritis
    Rajalingam S, Sakthiswary R, Hussein H
    Arch Rheumatol, 2017 Mar;32(1):15-20.
    PMID: 30375543 DOI: 10.5606/ArchRheumatol.2017.5960
    Objectives: This study aims to determine the predictors of poor sleep quality in rheumatoid arthritis (RA).

    Patients and methods: This was a monocentric, cross sectional, case-control study which was conducted at the Putrajaya Hospital, Malaysia. We recruited 46 patients with RA (3 males; 43 females; mean age 48.15±14.96) and 46 age and sex-matched healthy controls (3 males; 43 females; mean age 47.11±12.22). RA patients were assessed for their disease activity based on disease activity score in 28 joints, disease damage based on radiographic erosions, and functional status based on Health Assessment Questionnaire Disability Index. The Pittsburgh Sleep Quality Index (PSQI) scores were determined by interviewing all the subjects. Subjects with RA were further subdivided based on their PSQI scores as "good sleepers" with PSQI scores of <5 and "poor sleepers" with PSQI scores of ≥5.

    Results: The percentage of poor sleepers was significantly higher among RA patients (47.83% versus 9.57%). Median scores of 5 out of 7 components of the PSQI were higher among RA patients compared to controls. Among poor sleepers with RA, a significantly higher proportion tested positive for anti-citrullinated cyclic peptide autoantibodies (p=0.037). Besides, poor sleepers had significantly higher median Health Assessment Questionnaire Disability Index (p=0.017) than good sleepers. However, both Health Assessment Questionnaire Disability Index (p=0.968) and anti-citrullinated cyclic peptide (p=0.431) were insignificant when entered in the equation of a logistic regression model.

    Conclusion: The findings of this study demonstrate a link between functional disability, anti-citrullinated cyclic peptide antibodies, and sleep quality in RA.
    Matched MeSH terms: Arthritis, Rheumatoid
  16. Fulltext Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
    Too CL, Murad S, Hansson M, Alm LM, Dhaliwal JS, Holmdahl R, et al.
    Arthritis Rheumatol, 2017 01;69(1):58-69.
    PMID: 27483449 DOI: 10.1002/art.39827
    OBJECTIVE: Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects.

    METHODS: A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.

    RESULTS: Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr  = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr  = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr  = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr  = 3.64 × 10-57 ) were significantly lower.

    CONCLUSION: Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

    Matched MeSH terms: Arthritis, Rheumatoid/immunology*
  17. Fulltext Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis
    Too CL, Murad S, Dhaliwal JS, Larsson P, Jiang X, Ding B, et al.
    Arthritis Res Ther, 2012;14(6):R250.
    PMID: 23164236 DOI: 10.1186/ar4093
    INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.
    METHODS: A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations.
    RESULTS: The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)).
    CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.
    Matched MeSH terms: Arthritis, Rheumatoid/ethnology; Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/immunology
  18. Fulltext Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA)
    Too CL, Yahya A, Murad S, Dhaliwal JS, Larsson PT, Muhamad NA, et al.
    Arthritis Res Ther, 2012;14(2):R89.
    PMID: 22537824 DOI: 10.1186/ar3813
    INTRODUCTION:Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent.
    METHODS: A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated.
    RESULTS: In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA.
    CONCLUSIONS: The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.
    Matched MeSH terms: Arthritis, Rheumatoid; Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/immunology; Arthritis, Rheumatoid/epidemiology
  19. Fulltext DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis
    Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, et al.
    Arthritis Res Ther, 2017 03 29;19(1):71.
    PMID: 28356135 DOI: 10.1186/s13075-017-1276-2
    BACKGROUND: Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.

    METHODS: We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.

    RESULTS: We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.

    CONCLUSIONS: We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.
    Matched MeSH terms: Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/immunology
  20. The association between HLA genes and radiological erosions in Malaysian patients with rheumatoid arthritis
    Yeap SS, Mohd A, Kumar G, Kong KF, Chow SK, Goh EM, et al.
    Autoimmunity, 2007 May;40(3):187-90.
    PMID: 17453717 DOI: 10.1080/08916930701233755
    OBJECTIVE:
    To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).

    METHODS:
    In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP) - PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen-Dale method. Demographic data and treatment given to the patients were obtained from their case records.

    RESULTS:
    Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.

    CONCLUSIONS:
    In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.
    Matched MeSH terms: Arthritis, Rheumatoid; Arthritis, Rheumatoid/genetics*; Arthritis, Rheumatoid/pathology*; Arthritis, Rheumatoid/radiography
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