POS0355 ASSOCIATIONS BETWEEN HLA-DRB1 SHARED EPITOPES ALLELES AND ANTI-RA33 ANTIBODIES IN DIFFERENT SUBSETS OF RHEUMATOID ARTHRITIS IN MALAYSIAN POPULATION

Background:The mechanisms affecting anti-RA33 antibody’s involvement in RA pathogenesis is still unclear. Refining our understanding of anti-RA33’s role in RA in relation to known RA-associated genes and serological elements is needed.Objectives:We investigated the relationship between RA-associated HLA-DRB1 epitope (SE) allele and presence of anti-RA33 antibodies in different serological subsets of rheumatoid arthritis in a Malaysian population.Methods:Serum samples from 550 RA cases comprising seronegative (negative for anti-CCP2, IgG and IgM, n=250), seropositive (triple-autoantibody positive, n=150), singular anti-CCP2 positive (n=100), and double RF positive RA (n=50) were chosen from the Malaysian Epidemiological Investigations of RA (MyEIRA) case-control study. Three hundred MyEIRA population controls were used for comparison. All serum samples were assayed using a commercial anti-RA33 ELISA kit. All genetic samples were genotyped for four-digit HLA-DRB1 alleles using the PCR-SSO method on Luminex platform.Results:The proportions of anti-RA33 positive was 20.9% in all RA cases (i.e. 34% in RF only positive RA; 25% in seropositive RA; 18% in seronegative RA and 18% in anti-CCP2 only positive RA). The HLA-DRB1 shared epitope alleles were significantly associated with anti-RA33 positive in the seropositive RA subgroup (OR=6.9, 95% CI 1.4-34.8; p=0.02). We observed significant association between anti-RA33 negative and HLA-DRB1 SE alleles among the seropositive RA patients (OR=4.5, 95% CI 2.8-7.2; p<0.001) and among CCP only positive RA (OR=4.4; 95% CI 2.6-7.4; p<0.01). No association was observed between anti-RA33 status and HLA-DRB1 SE alleles in seronegative RA and RF only positive RA.Conclusion:The HLA-DRB1 SE alleles increased the risk of seropositive and CCP only positive RA independent of anti-RA33 positivity.References:[1]Boeters, Debbie M et al. “The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts.” Seminars in arthritis and rheumatism vol. 47,2 (2017): 170-174.[2]de Brito Rocha, Sara et al. “Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis.” Advances in rheumatology (London, England) vol. 59,1 2. 17 Jan. 2019.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).Disclosure of Interests:None declared

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OP0096 EXPOSURE TO DENGUE INFECTION DO NOT RAISE RISK OF RHEUMATOID ARTHRITIS: FINDINGS FROM THE MALAYSIAN EPIDEMIOLOGICAL INVESTIGATION OF RHEUMATOID ARTHRITIS (MYEIRA) CASE-CONTROL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1684 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 53.1-53

Author(s):

L. K. Tan ◽

C. L. Too ◽

A. F. Nurul-Aain ◽

A. A. Siti-Aisyah ◽

S. Wahinuddin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Ethnic Groups ◽

Antibody Level ◽

Dengue Infection ◽

The Other ◽

Director General ◽

Igg Antibody ◽

Ministry Of Health ◽

Malaysian Population ◽

Mixed Ethnicity

Background: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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Insulin Resistance and Lipid Profile in Rheumatoid Arthritis Patients in Rheumatoid Arthritis Patients in Bangladesh

Journal of Medical Science & Research ◽

10.47648/jmsr.2011.v1601.02 ◽

2011 ◽

Vol 16 (Number 1) ◽

pp. 9-12 ◽

Cited By ~ 1

Author(s):

F Alam ◽

S S Chowdhury ◽

R Ishrat ◽

T Mehdi ◽

R Karim

Keyword(s):

Rheumatoid Arthritis ◽

Case Control Study ◽

Case Control ◽

Research Activity ◽

Rheumatic Arthritis ◽

Face To Face ◽

Medical University ◽

The Relationship ◽

Control Study ◽

Structured Questionnaire

There has been a great deal of research activity focusing on the relationship between insulin resistances (IR), hyperlidemia and Rheumatic arthritis (RA). It appears to be a general agreement that IR and hyperlipidaemia are commonly seen in patinas with RA. A case-control study was done among 45 RA patients and 42 healthy controls. The study was conducted in the outpatient department of Bangabandhu Sheikh Mujib Medical University (BSMMU). A structured questionnaire was used to collect data through face-to-face interview. TO and LDL were significantly higher and HDL was lower in comparison to those of control and associated with IR. Hyperlipidemias are associated with RA in Bangladeshis.

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The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study

Arthritis Research & Therapy ◽

10.1186/s13075-021-02431-z ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Lay Kim Tan ◽

Chun Lai Too ◽

Lina Marcela Diaz-Gallo ◽

Sulaiman Wahinuddin ◽

Ing Soo Lau ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Amino Acid ◽

Fine Mapping ◽

Case Control Study ◽

Case Control ◽

Caucasian Population ◽

Stepwise Logistic Regression ◽

Malaysian Population ◽

Control Study

Abstract Background Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy. Methods We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region. Results We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30–5.49, PGWAS = 7.22 × 10−29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37–0.62, PGWAS = 2.58 × 10−08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09–0.30, PGWAS = 1.60 × 10−09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia. Conclusions Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.

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Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case–control study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208278 ◽

2015 ◽

Vol 75 (6) ◽

pp. 997-1002 ◽

Cited By ~ 41

Author(s):

Chun Lai Too ◽

Nor Asiah Muhamad ◽

Anna Ilar ◽

Leonid Padyukov ◽

Lars Alfredsson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Occupational Exposure ◽

Case Control Study ◽

Population Based ◽

Case Control ◽

Dust Exposure ◽

Environment Interaction ◽

Malaysian Population ◽

Increased Risk ◽

Control Study

ObjectivesLung 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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Comorbidities at diagnosis of rheumatoid arthritis: a population-based case-control study

Rheumatology ◽

10.1093/rheumatology/keaa856 ◽

2020 ◽

Author(s):

Liselotte Tidblad ◽

Helga Westerlind ◽

Bénédicte Delcoigne ◽

Johan Askling ◽

Saedis Saevarsdottir

Keyword(s):

Rheumatoid Arthritis ◽

General Population ◽

Case Control Study ◽

Neurological Diseases ◽

Population Based ◽

Case Control ◽

Comorbidity Burden ◽

Population Controls ◽

Control Study ◽

New Onset

Abstract Objectives Comorbidities contribute to the morbidity and mortality in rheumatoid arthritis (RA), and are thus important to capture and treat early. In contrast to the well-studied comorbidity risks in established RA, less is known about the comorbidity pattern up until diagnosis of RA. We therefore compared if the occurrence of defined conditions, and the overall comorbidity burden at RA diagnosis, is different from that in the general population, and if it differs between seropositive and seronegative RA. Methods Using Swedish national clinical and demographic registers, we identified new-onset RA patients (n = 11 086), and matched (1:5) to general population controls (n = 54 813). Comorbidities prior to RA diagnosis were identified in the Patient and Prescribed Drug Registers, and compared using logistic regression. Results At diagnosis of RA, respiratory (OR = 1.58, 95% CI = 1.44–1.74), endocrine (OR = 1.39, 95% CI = 1.31–1.47), and certain neurological diseases (OR = 1.73, 95% CI = 1.59–1.89) were more common in RA vs controls, with a similar pattern in seropositive and seronegative RA. In contrast, psychiatric disorders (OR = 0.87, 95% CI = 0.82–0.92) and malignancies (OR = 0.88, 95% CI = 0.79–0.97) were less commonly diagnosed in RA vs controls. The comorbidity burden was slightly higher in RA patients compared with controls (p< 0.0001). Conclusion We found several differences in comorbidity prevalence between patients with new-onset seropositive and seronegative RA compared with matched controls from the general population. These findings are important both for our understanding of the evolvement of comorbidities in established RA and for early detection of these conditions.

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