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Fulltext Association of Immunoglobulin G abnormalities in diseases: a mini review

Foong, Audrey Kow Siew, Nuha Fahimah Binti Wan Zahidi, Chau, Ling Tham

Life Sciences, Medicine and Biomedicine, 2018;2(1):24-39.
MyJurnal

Immunoglobulins are antibodies that play important roles in preserving our immune system. They have the ability to initiate humoral responses and remove antigen from the body. Out of the five major isotypes of immunoglobulins, IgG are most abundantly found in human serum. Abnormalities – deficiency or elevation in the level of IgG are found to be associated to the occurrence of several autoimmune diseases. These may include rheumatoid arthritis, Crohn’s disease, Mikulicz’s disease, Kuttner’s tumour and Hashimoto’s thyroiditis. Apart from autoimmune diseases, IgG has been found to play a role in initiating anaphylaxis, a severe and life threatening form of allergy and lately it has been discovered in cases of dengue virus infection too. It is important to acknowledge the roles of IgG on diseases especially subclass IgG4 which the elevation has been tied to numerous diseases such as Kuttner’s tumour and Hashimoto’s thyroiditis hence termed IgG4-related diseases. In addition, the roles of IgG in anaphylaxis are of importance, too, as IgG has been used in allergy immunotherapy. Hence, this review is a mini compilation of effects of IgG abnormalities based on their subclasses. Hopefully it will provide insightful understanding on the development of diagnostic and therapeutic courses for the aforementioned IgG abnormalities in the future.

Matched MeSH terms: Arthritis, Rheumatoid
Fatigue and associated factors in a multi-ethnic cohort of rheumatoid arthritis patients

Lee HJ, Pok LSL, Ng CM, Yahya F, Sockalingam S, Tee YC, et al.

Int J Rheum Dis, 2020 Aug;23(8):1088-1093.
PMID: 32597545 DOI: 10.1111/1756-185X.13897

INTRODUCTION: Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life.
OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.
METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).
RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/ethnology; Arthritis, Rheumatoid/physiopathology
Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

Tan BE, Lim AL, Kan SL, Lim CH, Ng YF, Tng SLC, et al.

Rheumatol Int, 2017 Jun;37(6):905-913.
PMID: 28389855 DOI: 10.1007/s00296-017-3705-6

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/ethnology
Fulltext Morsellized Allograft and Acetabular Reconstruction Cage: Follow â€“ up of 2 to 9 years

Abbas, A.A., Merican, A.M., Mohamad, J.A.

Malays Orthop J, 2007;1(1):5-7.
MyJurnal

We report the outcome of 32 patients who underwent total hip replacement (THR) augmented with morsellized fresh frozen femoral head allografts and acetabular reconstruction cages. Nine patients underwent primary THR and 23 patients underwent revision THR. Follow-up ranged from two to 9 years. Two most common indications for the procedures as reported in literature were rheumatoid arthritis and aseptic loosening of the hip. All but one patient achieved good outcome with radiographs showing full incorporation of bone grafts and no evidence of loosening of the implants. Morsellized bone grafting used with acetabular reinforcement devices is valuable for addressing severe acetabular deficiencies.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Determinants of comorbidity in rheumatoid arthritis: influence of demographic and duration of illness

Chin SN, Abdullah N, Poh LP

Journal of Advanced Research Design, 2015;22(1):13-22.
MyJurnal

Rheumatoid arthritis (RA) is a chronic, disabling autoimmune disease which affects about 5 in 1000 people in Malaysia. Patients with RA are at increased risk of developing comorbid conditions. This research aims at determining these relationships between demographic, duration of illness and comorbidity in RA via a multiple binary logistic (MBL) regression analysis based on the 102 patients’ information (23 males; 79 females) obtained from the rheumatoid clinic of the Queen Elizabeth Hospital in Kota Kinabalu. The relationship of the RA patients with comorbid conditions was studied with focus on the demographic and duration of illness. The variables obtained for analysis were the comorbid conditions namely, hypertension and hyperlipidemia, age, duration of illness, gender, ethnicity, household income and education level. From six independent variables, two were quantitative would be analyzed, while four were categorical, and would be transformed into dummy variables. Four phases in a model-building approach were executed where two models were formed where Model I predicted the probability of occurrence of hypertension with age of patients and first order interaction between duration of illness before diagnosis and household income of less than RM1000 had positive effects on the model, while Model II predicted the occurrence of hyperlipidemia among the RA patients with age of patients and first order interaction variable between gender(female) and age were the contributing factors.
Study site: Rheumatoid clinic, Queen Elizabeth Hospital (QEH), Kota Kinabalu, Sabah, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis

Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, Yeap SS

Int J Rheum Dis, 2018 May;21(5):992-1000.
PMID: 28217867 DOI: 10.1111/1756-185X.13048

AIM: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.

METHODS: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).

RESULTS: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

CONCLUSIONS: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Semblance; Klinik Pakar Puchong, Puchong, Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/ethnology; Arthritis, Rheumatoid/pathology*
Fulltext Anti-cyclic citrullinated peptide antibody and periodontal status in rheumatoid arthritis patients

Mohamad WMW, Jia SK, Ghazali WSW, Taib H

Pak J Med Sci, 2018 9 8;34(4):907-912.
PMID: 30190751 DOI: 10.12669/pjms.344.15007

Objectives: Studies have shown that periodontal disease and Rheumatoid Arthritis (RA) shared similar pathogenesis. Anti-Cyclic Citrullinated Peptide anibodies (anti-CCP) has recently been used for diagnosis of RA. Thus, this study aimed to assess the levels of anti-CCP antibodies and periodontal status in RA patients.
Methods: Forty four RA patients were included in this study. The blood samples were analysed for anti-CCP levels. Plaque Score (PS), Gingivitis Score (GS), Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) were recorded for assessment of periodontal status. Relevant clinical information was obtained from medical records.
Results: Mean anti-CCP level was 180.8 ± 290.3 Unit/ml. The results showed that 27.3% patients had poor oral hygiene (PS >60%; mean anti-CCP 84.22 ± 167.51 Unit/ml), 52.3% had generalized gingivitis (mean anti-CCP 145.07 ± 269.17 Unit/ml), and 20.5% had mean CAL of >3mm (mean anti-CCP 56.81 ± 119.02 Unit/ml). None of patients presented with deep PPD > 4mm. The levels of anti-CCP showed no significant association with periodontal status (p=0.27).
Conclusion: Most RA patients were positive for anti-CCP antibodies and presented with generalized gingivitis. Oral hygiene education should be reinforced in RA patients to prevent further progression of periodontal disease. Nevertheless, studies with larger sample size should be carried out to obtain more conclusive findings.
Study site: Rheumatology Clinic and Dental Clinic of Hospital Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Epidemiology of rheumatoid arthritis, clinical aspects and socio-economic determinants in Pakistani patients: A systematic review and meta-analysis

Naqvi AA, Hassali MA, Aftab MT

J Pak Med Assoc, 2019 Mar;69(3):389-398.
PMID: 30890833

OBJECTIVE: The study aimed to evaluate literature on rheumatoid arthritis disease in Pakistani patients, to have an understanding about its epidemiology, clinical aspects and socio-economic determinants.
METHODS: The review study was conducted from December 2017, to May 2018. An online search was conducted in international and local health databases using appropriate search keywords as well as scanning reference lists of related articles. Literature published after year 2000 that reported epidemiological, demographic, clinical and socioeconomic data of Pakistani rheumatoid arthritis patients was included. Meta-analysis was performed where possible. This systematic review was registered on the international prospective register of systematic reviews PROSPERO (CRD42018090582).
RESULTS: Of the 334 research articles found, 29 (8.7%) were selected. Patients were mostly females, but no study explored impact of disease on household and family role functioning of rheumatoid arthritis-affected women in Pakistan. Most patients were uneducated (55%) and unemployed; had low disease knowledge (N = 149, 74.5%) and poor adherence to disease-modifying anti-rheumatic drugs (N = 23, 23%). Point prevalence of rheumatoid arthritis reported from Karachi was high at 26.9%. Moderate disease activity, i.e., 4.5}0.7 and mild functional disability (N = 66, 51.6%) were seen in RA patients. Almost half (N = 799, 46.9%) had comorbidities. Almost a fifth proportion of RA patients had dyslipidaemia as a comorbidity (N = 134, 16.77%) and higher cardiovascular risk score as modifiable risk factor. Undiagnosed depression (N = 134, 58.3%) and low bone mineral density (N = 93, 40.6%) were reported in RA patients. Direct monthly treatment cost of disease was significantly high considering patients' socio-economic status, i.e., USD 16.47 - 100.68. Most commonly used drug was methotrexate.
CONCLUSIONS: There is a paucity of data on Pakistani rheumatoid arthritis patients' demographic and socio-economic parameters, especially the gender element.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy; Arthritis, Rheumatoid/economics; Arthritis, Rheumatoid/epidemiology*
Fulltext The atypical presentation of rheumatoid arthritis in an elderly woman: a case report

Devaraj NK

Ethiop J Health Sci, 2019 Jan;29(1):957-958.
PMID: 30700964 DOI: 10.4314/ejhs.v29i1.18

The diagnosis of rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen. This includes conditions such as rheumatoid arthritis which needs early diagnosis to start disease modifying drugs (DMARDs) which can improve the prognosis and prevent further joint erosion and organ damage. This case report focused on a similar scenario in an elderly woman initially thought to have osteoarthritis but was diagnosed later with rheumatoid arthritis which brought much relief to her current predicament.

Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/drug therapy
Ficus carica and bone health: a systematic review

Ruszymah Idrus, Nur Qisya Afifah Veronica Sainik, Ayu Suraya Ansari, Rabiatul Adawiyah Razali, Abid Nordin, Aminuddin Saim, et al.

Sains Malaysiana, 2018;47:2741-2755.

Ficus carica, a native plant to the Middle East and Western Asia, is of high value in folk medicine. The therapeutic potential
of Ficus carica has led to the extensive studies in recent years, focusing on evaluating and validating its pharmacological
effect. The present systematic review summarizes the effectiveness of Ficus carica on promoting bone health focusing on
osteoporosis and rheumatoid arthritis via mineral contents and RANKL pathway. The search was done with Medline via
Ebscohost, Scopus and Google Scholar databases to obtain relevant articles published between 1946 and December
2016. The main inclusion criteria were research articles published in English that reported effect of Ficus carica on
bone health. The literature search returned 716 potentially relevant articles, whereby 5 met the inclusion criteria. This
systematic review concludes Ficus carica plays an important role in the promotion of bone health and can be a potential
pharmaceutical product in the future.

Matched MeSH terms: Arthritis, Rheumatoid
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*
Biomechanical analysis of rheumatoid arthritis of the wrist joint

Bajuri MN, Kadir MR, Amin IM, Ochsner A

Proc Inst Mech Eng H, 2012 Jul;226(7):510-20.
PMID: 22913098 DOI: 10.1177/0954411912445846

The wrist is the most complex joint for virtual three-dimensional simulations, and the complexity is even more pronounced when dealing with skeletal disorders of the joint such, as rheumatoid arthritis (RA). In order to analyse the biomechanical difference between healthy and diseased joints, three-dimensional models of these two wrist conditions were developed from computed tomography images. These images consist of eight carpal bones, five metacarpal bones, the distal radius and ulna. The cartilages were developed based on the shape of the available articulations and ligaments were simulated via mechanical links. The RA model was developed accurately by simulating all ten common criteria of the disease related to the wrist. Results from the finite element (FE) analyses showed that the RA model produced three times higher contact pressure at the articulations compared to the healthy model. Normal physiological load transfer also changed from predominantly through the radial side to an increased load transfer approximately 5% towards the ulnar. Based on an extensive literature search, this is the first ever reported work that simulates the pathological conditions of the rheumatoid arthritis of the wrist joint.

Matched MeSH terms: Arthritis, Rheumatoid; Arthritis, Rheumatoid/physiopathology*
Osteoarticular tuberculosis mimicking rheumatoid arthritis

Ong PS, Sulaiman W

Mod Rheumatol, 2012 Nov;22(6):931-3.
PMID: 22399018 DOI: 10.1007/s10165-012-0605-1

Tuberculosis (TB) remains a global burden despite extensive efforts to control it. TB arthritis commonly manifest as monoarthritis of weight-bearing joints. We report a rare presentation of osteoarticular TB involving multiple small joints of the hands, which mimicked rheumatoid arthritis (RA). Magnetic resonance imaging showed tenosynovitis. The patient was initially treated for seronegative RA but failed to respond. Subsequently, synovial biopsy led to the diagnosis. Antituberculosis treatment was given for 1 year.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*
Fulltext The clinical significance of interleukin-1 receptor antagonist +2018 polymorphism in rheumatoid arthritis

Ismail E, Nofal OK, Sakthiswary R, Shaharir SS, Sridharan R

PLoS One, 2016;11(4):e0153752.
PMID: 27105431 DOI: 10.1371/journal.pone.0153752

OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.
METHODS: Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).
RESULTS: The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.
CONCLUSIONS: C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.
Study site: Outpatient clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid/genetics*
Fulltext Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis

Burska AN, Sakthiswary R, Sattar N

PLoS One, 2015;10(6):e0128889.
PMID: 26110878 DOI: 10.1371/journal.pone.0128889

OBJECTIVE: Beyond the joints, TNFi (tumour necrosis factor inhibitor) therapy may confer systemic benefits in rheumatoid arthritis (RA). Several studies have investigated the role of TNFi on insulin resistance/sensitivity (IR/IS). This question is of general interest given the emerging evidence linking inflammation and insulin resistance. The main aim of this review was to summarise the published data and to determine the effects of TNFi on IR/IS.
METHODS: We searched the PubMed and ISI Web of Knowledge databases for studies which examined the effects of TNFi on IR/IS. The studies were assessed independently by two reviewers according to a pre-specified protocol. The data on Homeostatic Model Assessment for Insulin resistance (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were pooled and reported as standard difference in means (SDM) with 95% confidence interval (CI) using a random-effects model.
RESULTS: A total of eight studies with 260 subjects met the selection criteria. The duration of the studies was from 8 weeks to 12 months. There was statistically significant reduction in HOMA index in six out of eight studies and four reported significant increment in QUICKI. The pooled analysis revealed significant reduction in HOMA [SDM-0.148, 95%CI[-0.278 to -0.017], p=0.026] and increment in QUICKI [SDM 0.312, 95%CI[0.019 to 0.606], p=0.037] with TNFi.
CONCLUSION: There is emerging evidence to support that TNFi therapy improves IS and reduces IR in RA. Further, well conducted trials are needed to determine if such effects translate to lower incidence of diabetes in RA or other autoimmune conditions on biologic therapy.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*
Fulltext Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss

Crotti TN, Dharmapatni AA, Alias E, Haynes DR

J Immunol Res, 2015;2015:281287.
PMID: 26064999 DOI: 10.1155/2015/281287

The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR).

Matched MeSH terms: Arthritis, Rheumatoid/metabolism
HLA-DRB1 genes and susceptibility to rheumatoid arthritis in three ethnic groups from Malaysia

Kong KF, Yeap SS, Chow SK, Phipps ME

Autoimmunity, 2002 Jul;35(4):235-9.
PMID: 12482190

Worldwide population studies have generally agreed that rheumatoid arthritis (RA) is associated with a group of HLA-DRB1 alleles which share a common amino acid sequence at residues 70-74. This represents the first study to investigate the association of HLA-DRB1 genes with susceptibility to RA amongst Malay, Chinese and Indian ethnic groups in Malaysia. One hundred and thirty three RA patients and one hundred and sixty seven healthy controls were recruited. The HLA-DRB1 alleles were studied using the Phototyping method. The subtypes of HLA-DR4 were detected by "high resolution" PCR-SSP DRB1*04 typing techniques. The prevalence of HLA-DRB1*0405 was significantly higher in Malay patients with RA than in healthy controls (28.9 vs. 8.3%, p = 0.0016, OR = 4.48, 95% CI = 1.26-16.69). Similarly, DRB1*0405 was more common in Chinese RA patients than in controls (30.0 vs. 6.7%, p = 0.0029, OR = 6.00, 95% CI = 1.67-23.48). In addition, DRB1*0901 was a predisposing factor (32.0 vs. 6.7%,p = 0.0015, OR = 6.59, 95% CI = 1.85-25.64) and *0301/04 had a protective role (4.0vs. 25.0%, p = 0.00562, OR = 0.13, 95% CI = 0.02-0.62) in Malaysian Chinese RA. RA in Indians was associated with DRB1*1001 (51.1 vs. 8.5%,p = 0.00002, OR = 11.24, 95% CI = 3.13-44.18). DRB1*0701 (13.3 vs. 42.6%,p = 0.0022, OR = 2.73, 95% CI = 1.40-5.37) may have a protective effect. Therefore, in the Malaysian population, RA is primarily associated with the QRRAA motif, and we suggest that genetic factors play a crucial role in the pathogenesis of RA, compared to environmental factors.

Matched MeSH terms: Arthritis, Rheumatoid/genetics*
Fulltext Simultaneous bilateral total knee replacement

Lopez JM, Sivanantham M

Med J Malaysia, 1998 Sep;53 Suppl A:102-6.
PMID: 10968191

This paper summarises our experience of twenty one patients with degenerative arthritis treated by bilateral simultaneous total knee replacement (BSTKR) in Tawakal Hospital in a period of twenty two months vis. January 1994 to November 1995. The results were analysed according to the scoring system of Hospital for Special Surgery. The preliminary observations were encouraging, 90% excellent, 8% good and 2% fair results. The benefits, safety and cost effectiveness of the procedure as compared to the unilateral staged knee replacement are discussed. We recommend that BSTKR be routinely practised for appropriate situations in all institutions where the expertise and facilities are available.

Matched MeSH terms: Arthritis, Rheumatoid/surgery
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*
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*

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