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Fulltext Seroprevalence of small ruminant caprine arthritis encephalitis lentivirus among goats from selected small ruminant farms in Selangor, Malaysia

Jesse FFA, Bitrus AA, Abba Y, Raju VN, Hambali IU, Peter ID, et al.

Vet World, 2018 Feb;11(2):172-176.
PMID: 29657399 DOI: 10.14202/vetworld.2018.172-176

Background and Aim: Caprine arthritis encephalitis (CAE) is an important viral disease of small ruminants particularly in dairy goats with severe social and economic implication. Hence, this study was designed to determine the seroprevalence of CAE virus (CAEV) among goat population in selected small ruminant farms in Selangor and the risk factors associated with the occurrence of the disease.
Materials and Methods: Blood samples were collected from a total of 91 goats selected at random. Blood serum was harvested and used for competitive enzyme-linked immunosorbent assay test to detect antibodies against CAE virus.
Results: The result obtained showed that 8/91 (8.8%) of the goats were seropositive for CAEV. In addition, biosecurity management, source of origin and sex of the animal were observed to be important risk factors associated with the occurrence of CAE in goats.
Conclusion: The findings of this study affirmed that the seroprevalence of CAEV infection among goat population in small ruminant farms in Selangor, Malaysia, is low. However, there is need to institute strict control measures such as testing and culling positive animals or separation of infected animals from those that tested negative to the disease for effective eradication of the disease.

Matched MeSH terms: Arthritis; Arthritis-Encephalitis Virus, Caprine
Curcumin as an anti-arthritic agent in collagen-induced arthritic Sprague-Dawley rats

Zahidah A, Faizah O, Nur Aqilah K, Taty Anna K

Sains Malaysiana, 2012;41:591-595.

Curcuma longa or turmeric has long been used in traditional medicine by the local population in Malaysia as an antiinflammatory agent. It has been proven to contain natural antiarthritic compound called curcumin. Joints abnormality and destruction have been implicated in the pathogenesis of rheumatoid arthritis (RA) due to inflammatory reactions. In this study, collagen-induced arthritis (CIA) model was utilized to study the effects of curcumin on joint inflammation in Sprague-Dawley rats. Body weight measurement, arthritis score assessment and radiology score assessment were carried out at specific intervals throughout this study. The results showed that the mean arthritis and radiology scores for animal groups designated as CIA CurcuminC and CIA CurcuminT were significantly lower compared with the negative control (CIA OV) group respectively. The mean arthritis scores for CIA CurcuminC group is significantly lower compared with CIA CurcuminT group but there is no significant difference in the mean radiology scores between the CIA CurcuminC and CIA CurcuminT groups. In conclusion, the oral supplementation of curcumin at the dose of 110 mg/mL/kg/day has a potential to delay and improve joint abnormality and injury in Sprague-Dawley rats with CIA.

Matched MeSH terms: Arthritis, Experimental; Arthritis, Rheumatoid
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*
Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients

Wan Jiun T, Taib H, Majdiah Wan Mohamad W, Mohamad S, Syamimee Wan Ghazali W

Int Immunopharmacol, 2023 Nov;124(Pt B):110940.
PMID: 37722261 DOI: 10.1016/j.intimp.2023.110940

Porphyromonas gingivalis (P. gingivalis) is the primary periodontal pathogen involved in protein citrullination, which triggers the production of anti-cyclic citrullinated peptide (anti-CCP) antibodies, exacerbating rheumatoid arthritis (RA). This study aims to evaluate the amount of P. gingivalis and its association with anti-CCP antibodies in RA patients with periodontitis. This cross-sectional study involves 100 RA patients with a mean age of 52.36 (SD 13.90) years. Smokers and patients with other uncontrolled systemic diseases were excluded. Disease Activity Score-28 (DAS-28) was used to determine RA disease severity. Periodontal parameters were examined to determine periodontal status. Subsequently, plaque samples were collected from the subgingival periodontal pocket for assessment of P. gingivalis bacterial load using the loop-mediated isothermal amplification method. Blood samples (5 ml) were obtained from all participants to analyse anti-CCP antibody levels. Data was analysed by using SPSS version 24.0. Most participants were female (85.0%) and had low RA disease severity (62%). The mean RA disease duration was 7.77 (SD 6.3) years, with a mean DAS-28 of 3.17 (SD 1.0). Forty-seven per cent of participants had periodontitis, but all periodontal parameters were not associated with RA disease activity (P = 0.38). P. gingivalis bacterial load ranged from 10 to 109 copies/μl. Fifty-five per cent of the collected samples showed positive anti-CCP antibody levels, but no significant association was observed with the P. gingivalis bacterial load (P = 0.58). Considering the study's limitations, although periodontitis is prevalent among RA patients, there is a lack of association between P. gingivalis bacterial load and anti-CCP antibody levels, which should be investigated further.

Matched MeSH terms: Arthritis, Rheumatoid*
Juvenile spondyloarthropathy: an important clinical lesson to remember

Sridharan R, Ngiu CS, Shaharir SS, Said MS

BMJ Case Rep, 2015;2015.
PMID: 26677159 DOI: 10.1136/bcr-2015-213220

Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted.

Matched MeSH terms: Arthritis, Juvenile
Fulltext Anti-cyclic citrullinated peptide antibody is a good indicator for the diagnosis of rheumatoid arthritis

Abdul Wahab A, Mohammad M, Rahman MM, Mohamed Said MS

Pak J Med Sci, 2013 May;29(3):773-7.
PMID: 24353626

Objectives: Anti-cyclic citrullinated peptide (CCP) antibody has recently been used in the classification
of rheumatoid arthritis (RA). This antibody is more specific than rheumatoid factor (RF) for the diagnosis of RA. The study objectives were to determine the sensitivity, specificity, positive and negative predictive values of anti-CCP in RA diagnosis.
Methodology: Eighty RA patients and 80 non-RA individuals were included in the study. Blood was collected from both arms of study subjects and tested for anti-CCP and RF antibodies. Relevant clinical information and laboratory profiles of the RA patients were evaluated using patients’ medical records and Integrated Laboratory Management System (ILMS), respectively.
Results: The sensitivity and specificity of anti-CCP were 35% and 100% respectively. The positive and
negative predictive values were 100% and 61%, respectively. Positive anti-CCP was found significantly
associated with multiple joint pain (p < 0.001) and hand’s joints pain (p=0.01), symmetrical joints
involvement (p=0.015) and high CRP value (p < 0.001). Anti-CCP was also found to have positive association with RF (p < 0.001).
Conclusion: Anti-CCP is highly specific for the diagnosis of RA. High positive predictive value should be taken into consideration for effective treatment.
KEY WORD: Rheumatoid arthritis, anti-CCP, Rheumatoid factor, Sensitivity, Specificity, Positive predictive value, Negative predictive value.
Study site: Rheumatology Unit, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case-control study

Yahya A, Bengtsson C, Lai TC, Larsson PT, Mustafa AN, Abdullah NA, et al.

Mod Rheumatol, 2012 Aug;22(4):524-31.
PMID: 22006120 DOI: 10.1007/s10165-011-0544-2

We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.

Matched MeSH terms: Arthritis, Rheumatoid/ethnology; Arthritis, Rheumatoid/etiology*; Arthritis, Rheumatoid/immunology
Fulltext Analytical and diagnostic performance of an automated anti-CCP assay

Pavai S, Sargunan S, Zain AA, Chow SK

Malays J Pathol, 2011 Dec;33(2):101-6.
PMID: 22299210 MyJurnal

Aim: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the diagnostic and analytical performances of the automated anti-CCP assay.
Materials and Method: Sera from 80 patients with established RA, 65 from other rheumatic diseases (non-RA) and 55 from healthy controls were studied using second generation anti-CCP. Rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP fi ndings. Serum pools were used to determine the precision and linearity.
Results: At a cut-off of 7.4 U/ml for anti-CCP, the sensitivity and specificity for RA were 65% and 98% respectively. RF had a sensitivity of 58% and a lower specifi city of 93 % than anti-CCP. Conclusion: The high specificity of the assay suggests that anti-CCP is useful in the diagnosis of rheumatoid arthritis and in our cohort of study population anti-CCP exhibits a better diagnostic value than RF. A considerable proportion (28%) of RF-negative RA patients were anti-CCP positive. Based on analytical performance of the assay, we conclude that full automation and high throughput features of AxSYM makes it an ideal platform for routine testing of anti-CCP.
Study site: Rheumatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/immunology
A cross-sectional study of diastolic dysfunction in rheumatoid arthritis and its association with disease activity

Abdul Muizz AM, Mohd Shahrir MS, Sazliyana S, Oteh M, Shamsul AS, Hussein H

Int J Rheum Dis, 2011 Feb;14(1):18-30.
PMID: 21303478 DOI: 10.1111/j.1756-185X.2010.01593.x

AIMS: The aim of this study was to evaluate the left ventricular (LV) diastolic dysfunction in rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations and to estimate whether there is any correlation between RA disease severity and disability and LV diastolic dysfunction.
METHODS: The study was a cross-sectional study involving 53 patients (47 female and 6 male) with RA without clinically evident heart disease and 53 healthy subjects (47 female and 6 male) who served as a control group. Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects.
RESULTS: Of 17 cardiac parameters assessed, only two were abnormal. None of the specific cardiac diastolic dysfunction parameters were significantly different in RA patients compared to the control group. There was no significant correlation between diastolic function values in RA patients and value of Disease Activity Score 28 (DAS-28) and value of Health Assessment Questionnaires Disability Index (HAQDI). Atrial (A) wave velocity was greater in RA patients compared to the control group (0.71 [0.58-0.83] vs. 0.61 [0.51-0.71]; P < 0.04). However, interventricular relaxation time (IVRT) ([73.08 ± 9.92 vs. 70.74 ± 9.02], P = 0.207), lower E/A ratio (1.27 [1.02-1.56] vs. 1.42 [1.20-1.68], P = 0.102), diastolic dysfunction parameters according to Redfield Classification (25 [47.2%] vs. 27 [50.9%] P = 0.56), diastolic dysfunction using E/A (P = 0.321) and tissue doppler imaging (E/E') (P = 0.148) were not different.
CONCLUSION: Prevalence of diastolic dysfunction in the rheumatoid arthritis group (47.2%) was not different from controls (50.9%). LV diastolic function had no significant correlation with RA disease severity and duration of disease.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/epidemiology; Arthritis, Rheumatoid/physiopathology*
The pattern and clinical manifestations of rheumatoid arthritis in Sarawak General Hospital

Teh CL, Wong JS

Clin Rheumatol, 2008 Nov;27(11):1437-40.
PMID: 18773254 DOI: 10.1007/s10067-008-0945-6

The aim of our study is to describe the pattern, clinical features, treatment regimes, and disease activity among the patients treated for rheumatoid arthritis (RA) in the Sarawak General Hospital. We performed a cross-sectional study of all patients with a diagnosis of RA who received treatment at the General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital over a 1-year period from 1st June 2006 to 31st May 2007. Demographic data, clinical features, and disease activity of all 154 patients were collected for statistical analysis. Rheumatoid arthritis afflicts all the major racial groups in Sarawak including the native population. Our patients have a mean disease duration of 5.4 years (SD 5.69) and a mean duration of delay in diagnosis RA and initiation of disease-modifying antirheumatic drug (DMARD) treatment of 42.9 months (SD 60.1). They have a low rate of interstitial lung disease (6.5%) and rheumatoid nodules (4.5%). Rheumatoid factor was positive in 65.5% of our patients. They have a mean Disease Activity Score (DAS) 28 score of 4.28 (SD 1.33). Only 12.5% of our patients are in remission with DAS 28 < 2.6 and 30.9% of our patients are having high disease activity with DAS 28 > 5.1. Despite the high usage of DMARDs in Sarawak (>80%), our patients have severe disease with high disease activity indices. This is most likely due to delay in diagnosis and initiating DMARDs in RA patients in Sarawak.

Study site: General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/epidemiology*; Arthritis, Rheumatoid/physiopathology
The effect of disease activity on fat-free mass and resting energy expenditure in patients with rheumatoid arthritis versus noninflammatory arthropathies/soft tissue rheumatism

Arshad A, Rashid R, Benjamin K

Mod Rheumatol, 2007;17(6):470-5.
PMID: 18084698 DOI: 10.1007/s10165-007-0628-1

Rheumatoid arthritis (RA) is a chronic joint disease of undetermined cause that is associated with significant disability. Low-grade fever, anemia, and weight loss are recognized extra-articular features associated with increased disease activity. Weight loss and cachexia are well-established features of RA. The mechanism behind weight loss in RA is not known and may be multifactorial. Reduced energy intake and hypermetabolism are the major two factors frequently implicated in the etiology of RA cachexia. One would expect the effect of the above two factors to be highest during increased disease activity and lowest during remission. The purpose of this study was: (a) to establish whether in RA patients changes in body composition mirror changes in disease activity, (b) to investigate the relation between the energy expenditures and weight loss, (c) to examine the dietary energy intake and its role in weight loss in RA patients, and (d) to investigate the relation between the cytokine interleukin (IL)-6 and other variables including resting energy expenditure (REE), body composition, and acute phase reactants. Fourteen patients with RA were age-, sex-, and race-matched with 14 controls from patients with noninflammatory diseases/soft tissue rheumatism. The measurements included the following: disease activity assessment, anthropometric measurements, indirect calorimetry, and measurements of dietary intake. Blood was collected to measure the acute-phase reactants and IL-6 levels. We demonstrated that loss of fat-free mass (FFM) might accelerate during times of increased disease activity and is only partially restored during periods of reduced disease activity. This probably means that the extent of cachexia in RA patients is determined by the frequency and intensity of disease activity (flare) for a given disease duration. Hypermetabolism with increased REE was more evident during increased disease activity. Hypermetabolism in the face of increased energy intake continued to cause loss of the FFM. Interleukin-6 correlates with increased REE and erythrocyte sedimentation rate. There was no direct association between IL-6 level and low FFM. We conclude that loss of FFM is common in RA, cytokine production in RA is associated with altered energy metabolism, and preservation of FFM is important in maintaining good quality of life in patients with RA.
Study site: Rheumatology clinic, Putra Specialist Centre, Kedah

Matched MeSH terms: Arthritis, Rheumatoid/complications*; Arthritis, Rheumatoid/metabolism; Arthritis, Rheumatoid/physiopathology
Fulltext Can intra-articular therapies prior to total knee arthroplasty increase the risk of periprosthetic infection?

Yeo QY, Lye DC, Sathappan SS

Med J Malaysia, 2015 Feb;70(1):54-6.
PMID: 26032534

Intra-articular therapies, such as steroid injection, viscosupplement injection and acupuncture, are common non-surgical options for patients with osteoarthritis of the knee. With any intra-articular injection or acupuncture procedure, there is a potential for inoculation with bacteria leading to possible knee infection. The authors report a patient who incurred an acute infection found after a total knee arthroplasty attributed to prior acupuncture procedure done as part of conservative treatment.

Matched MeSH terms: Arthritis, Infectious
Fulltext Corticosteroids causing severe growth suppression in juvenile rheumatoid arthritis

Lyn PCW

Med J Malaysia, 1984 Dec;39(4):300-5.
PMID: 6544938

Two children with Juvenile Rheumatoid Arthritis (JRA) and severe growth suppression from corticosteroid therapy are described. Prolonged 'tailing-off' of steroids occurred during outpatients follow-up and this may be related to the high turnover of doctors involved. Suggestions for improving such follow-ups and caution against the continuous use of steroids are made.
Study site: Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

Matched MeSH terms: Arthritis, Juvenile/complications; Arthritis, Juvenile/drug therapy*; Arthritis, Rheumatoid
Fulltext Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study

Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.

Medicine (Baltimore), 2015 Jan;94(4):e468.
PMID: 25634192 DOI: 10.1097/MD.0000000000000468

Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/genetics
Fulltext Clinical and Radiological Study of Serum Fluoride in Relation to Knee Osteoarthritis

Singh VK, Rathore KS, Khan G, Rahim A, Rashid A, Chauhan S

Malays Orthop J, 2020 Nov;14(3):151-154.
PMID: 33403076 DOI: 10.5704/MOJ.2011.023

Introduction: Fluorosis has been associated with an increased risk of degenerative changes in the knee. Multiple studies have found an association between arthritis and elevated fluoride levels. We aim to delineate if elevated fluoride level has any direct correlation with the degree of radiological grading and clinical symptoms in knee arthritis.
Materials and Methods: A cross-sectional study of 80 knee arthritis patients was conducted from February 2017 to April 2018. Serum fluoride levels were measured and patient's pain scores, WOMAC scores and radiological grading were correlated with the elevated fluoride levels.
Results: In our study, 30 out of 80 patients had increased serum fluoride level. Statistically significant differences were noted in VAS score, WOMAC score and Kellgren and Lawrence radiological grades between patients with normal serum fluoride level and those with elevated fluoride level.
Conclusion: There is an increased risk of knee arthritis in patients with elevated blood fluoride levels and patients with increased fluoride levels are associated with more severe symptoms and radiographic disease.

Matched MeSH terms: Arthritis
Fulltext Novel therapeutic targets in rheumatoid arthritis

Sakthiswary R

Medicine & Health, 2018;13(1):12-19.
MyJurnal

Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune disease worldwide. Although incurable, there are available therapies to effectively control the disease activity and minimize the joint damage. Numerous cytokines, enzymes and other forms of proteins have been implicated in the disease process of RA. In general, pharmacological therapies in RA target cytokine pathways. Despite a wide variety of disease modifying antirheumatic drugs (DMARD), a significant proportion of patients remain refractory to the available therapies. Hence, the search for newer drugs with different modes of actions is an ongoing process. The present review aimed to explore novel therapeutic targets in RA based on data from the literature. Inhibitors of spleen tyrosine kinase, choline kinase, galectin 3 and hypoxia-inducible factor may have a promising role in the

Matched MeSH terms: Arthritis, Rheumatoid
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
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
Effects of vitamin D on disease activity and serum interleukin-6 in rheumatoid arthritis

Gopal K, Thevarajah M, Ng CM, Raja J

Int J Rheum Dis, 2019 May;22(5):834-841.
PMID: 30729713 DOI: 10.1111/1756-185X.13484

AIM: Vitamin D3 or 25(OH)D3 may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6). The aim of this study is to determine the clinical factors of vitamin D deficiency in multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 levels.
METHOD: One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D3 and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading doses of vitamin D3 and repeated assessments were done.
RESULTS: Vitamin D deficiency (<50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D3 levels compared to Malays and Indians (P

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/ethnology
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

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