Displaying publications 21 - 38 of 38 in total

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  1. 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
  2. Sakthiswary R, Omimah KJN, Endom I, Shaharir SS, Sridharan R
    Medicine & Health, 2016;11(2):209-217.
    MyJurnal
    The search for novel biomarkers has taken centre stage in the past decades of research in Rheumatoid Arthritis (RA). The purpose of the present study was to determine the correlation of serum matrix metalloproteinase-3 (MMP-3) with disease activity, joint damage and functional disability in patients with RA. We consecutively recruited RA patients who were under follow-up at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Information on the RA disease characteristics were obtained from the medical records and all RA patients were
    assessed for DAS28 (disease activity score based on 28 joints) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI). The hand radiographs of the RA patients were assessed for joint damage using the Modified Sharp Score (MSS). Serum MMP-3 levels from RA patients and healthy controls were measured using the ELISA method. We recruited a total of 77 RA patients and 18 healthy controls. The serum MMP-3 levels were significantly higher among the RA patients (p<0.05). There were significant correlations between the serum MMP3 levels and MSS (r =0.327) and HAQ-DI (r=0.256), both p<0.05. The mean serum MMP levels in RA patients with radiographic joint erosions was significantly higher than in patients without erosions (p<0.05). Likewise, the subjects with significant functional impairment i.e HAQ-DI ≥1; had significantly higher mean MMP-3 levels compared to RA patients without significant disability (p<0.05). Using multivariate analysis, HAQ-DI remained the independent predictor of serum MMP-3 in RA patients. Serum MMP-3 is a potential biomarker and predictor of radiographic joint damage and functional disability in RA.
    Keywords: acquired joint deformity, matrix metalloproteinases, rheumatoid arthritis
  3. Sakthiswary R, Rajalingam S, Norazman MR, Hussein H
    EXCLI J, 2012;11:624-631.
    PMID: 27847450
    Objective: Although osteoarthritis (OA) is widely accepted as a degenerative disease, autoimmune processes are believed to be involved in the pathogenesis. There are limited studies in this area and most of them focused on antibodies against chondrocyte membrane. In an attempt to address the paucity of evidence in this regard, we explored the clinical significance of antinuclear antibody (ANA) in primary osteoarthritis of the knee (OAK).
    Method: We studied 106 patients with primary osteoarthritis of at least 1 knee and 63 healthy controls from two tertiary centres in Malaysia from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1:40 and above was considered positive. Besides, the radiographs of bilateral knees were evaluated for grading, tibiofemoral compartment involvement and total knee replacement (TKR) implants. We compared the clinical characteristics between the ANA positive and ANA negative OAK cases.
    Results: The incidence of ANA positivity among the cases (39.4 %) was higher than the controls (27 %) but this difference was statistically insignificant (p=0.754). ANA positive cases showed significantly higher incidence of bilateral and Grade IV OAK with higher frequency of TKR. In the multiple regression analysis, bilateral OAK (p< 0.0001; odds ratio 9.00), Grade IV OAK (p<0.001, odds ratio 3.44) and TKR (p=0.009; odds ratio 2.97) remained associated with ANA positivity.
    Conclusions: ANA test is a potential prognostic tool in primary OAK and its positivity is associated with the clinical outcomes of bilateral, Grade IV OAK and TKR.
    Study site: Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur; Putrajaya Hospital, Wilayah Persekutuan
  4. Nor Hashimah AMM, Sakthiswary R, Shaharir SS, Wahab A
    Arch Rheumatol, 2019 Dec;34(4):387-394.
    PMID: 32010887 DOI: 10.5606/ArchRheumatol.2019.7243
    Objectives: This study aims to compare the serum pyridinoline (Pyd) levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of serum Pyd levels with radiographic joint erosions.

    Patients and methods: Serum samples were obtained from 48 patients with RA (9 males, 39 females; mean age 60.5 years; range 54 to 64 years) and 48 healthy controls (9 males, 39 females; mean age 57.5 years; range, 47 to 65 years). The enzyme-linked immunosorbent assay method was used for quantitative analysis of serum Pyd. Besides, all RA patients were assessed for joint damage based on modified Sharp score, disease activity based on disease activity score in 28 joints and functional capacity based on health assessment questionnaire-disability index.

    Results: The median serum Pyd levels were significantly higher among the RA patients (110.20 ng/mL [92.30-120.64]) compared to the controls (98.22 ng/mL [85.54-111.41]); p<0.05. RA patients with erosive disease had significantly higher serum Pyd levels (p=0.024). There was a significant positive correlation between serum Pyd levels and joint erosion score (r=0.285, p=0.049). The serum Pyd levels had no demonstrable association with disease activity or functional capacity. Steroid therapy did not appear to influence the levels of serum Pyd.

    Conclusion: Rheumatoid arthritis patients had significantly higher levels of serum Pyd compared to healthy controls. The serum Pyd levels had significant correlation with radiographic joint erosions which reflected disease damage.

  5. Sakthiswary R, Rajalingam S, Hussein H, Sridharan R, Asrul AW
    Clin Rheumatol, 2017 Dec;36(12):2683-2688.
    PMID: 28889184 DOI: 10.1007/s10067-017-3817-0
    The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = r = - 0.285, p = 0.014) in RA. The correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.
    Study site: Putrajaya Hospital, Malaysia
  6. Sakthiswary R, Syahrul Sazliyana S, Mohd Shahrir MS, Shahril NS, Hussein H
    EXCLI J, 2012;11:142-9.
    PMID: 27385955
    Tumor necrosis factor alpha (TNFα) is a multifunctional cytokine which plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Apart from its well recognized proinflammatory properties, it is known to interfere with lipid metabolism and erythropoiesis. We evaluated the effects of adalimumab on hematologic, lipid and inflammatory parameters using data from patients on adalimumab 40 mg fortnightly from 2 centers in Malaysia. Mean changes in laboratory values from baseline to Weeks 4, 12 and 24 were compared using paired T test and Wilcoxon signed-rank test. We studied 18 patients with RA who were on adalimumab 40 mg fortnightly. The inflammatory markers i.e. erythrocyte sedimentation rate and C reactive protein showed significant changes as early as at week 4 compared to baseline with p values of 0.003 and 0.005, respectively. From a baseline of high disease activity with a mean Disease Activity Score using 28 joint counts (DAS 28) of 5.3, there was a steady improvement in the disease activity and remission was achieved at week 24 with a DAS 28 of 2.4. The hemoglobin level improved at week 12 (p=0.013) and this was sustained till week 24. As opposed to previous studies, the LDL level significantly decreased at week 12 (p=0.015) and this change persisted till week 24 (p=0.001). The total cholesterol showed a similar pattern as the LDL. The pharmacodynamics of adalimumab therapy in rheumatoid arthritis extend beyond the joints with favorable effects on haemoglobin and lipid profile.

    Study site: Putrajaya Hospital and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  7. Kusyairi KA, Gendeh BS, Sakthiswary R, Shaharir SS, Haizlene AH, Yusof KH
    Lupus, 2016 Apr;25(5):520-4.
    PMID: 26657735 DOI: 10.1177/0961203315622279
    The purpose of this study was to determine the spectrum of nasal involvement in systemic lupus erythematosus (SLE) and its association with the disease activity of SLE based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This was a cross-sectional and observational study involving 73 stable SLE patients. All subjects were evaluated for the SLEDAI scores and had nasal endoscopic examination. The most commonly reported symptom was nasal congestion (31.5%) followed by nasal itchiness (26.0%), runny nose (20.5%) and nasal dryness (19.2%). Almost half (42.9%) of the subjects had nasal mucosal abnormalities, which included mucositis, crusting, ulceration, bifid middle turbinate, septal spur, Jacobson's organ, deviated nasal septum, bilateral inferior turbinate hypertrophy, everted uncinate process, nasopharynx cleft and torus palatinus. The median SLEDAI score for subjects with nasal symptoms was significantly higher than subjects without nasal symptoms (p 
  8. Sakthiswary R, Shaharir SS, Mohd Said MS, Asrul AW, Shahril NS
    Int J Rheum Dis, 2014 Nov;17(8):872-7.
    PMID: 25292482 DOI: 10.1111/1756-185X.12443
    AIM: The main objective of this study is to elucidate the role of immunoglobulin A (IgA) rheumatoid factor (RF) in predicting the clinical response to tumour necrosis factor α inhibitors (TNFi) among patients with rheumatoid arthritis (RA).
    METHOD: We recruited all patients with RA who were ever on TNFi for a minimum duration of 3 months at our centre. Based on the European League Against Rheumatism response criteria, subjects were further divided into responders and non-responders. Age-matched RA patients who were on conventional disease-modifying anti-rheumatic drugs and in remission were enrolled as controls. Subjects were tested for quantitative values of IgA, IgM, IgG RF and anti-citrulinated cyclic peptides (CCP). Further, all subjects were assessed for the disease activity score that includes 28 joints (DAS28) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI).
    RESULTS: A total of 31 subjects with RA who had received TNFi and 15 controls were enrolled in this study. There was a trend for the non-responders (n = 10) to have higher levels of all isotypes of RF and anti-CCP. However, only the IgA RF and anti-CCP levels were significantly higher in the non-responder group compared to the responders and controls (P = 0.001, P = 0.034, respectively). On multivariate analysis, only the IgA RF remained significant (OR 0.989; 95% CI 0.980-0.999; P = 0.026).
    CONCLUSION: IgA RF is potentially a novel predictor of response to TNFi in RA patients. Testing for pretreatment IgA RF levels could be a reasonable consideration before commencement of TNFi.
    Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  9. Sakthiswary R, Chan GY, Koh ET, Leong KP, Thong BY
    ScientificWorldJournal, 2014;2014:823763.
    PMID: 24971392 DOI: 10.1155/2014/823763
    BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore.
    METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis.
    RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512).
    CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

    Study site: Tan Tock Seng Hospital, Singapore
  10. Dalila AS, Mohd Said MS, Shaharir SS, Asrul AW, Low SF, Shamsul AS, et al.
    Kaohsiung J. Med. Sci., 2014 Jul;30(7):337-42.
    PMID: 24924839 DOI: 10.1016/j.kjms.2014.02.010
    The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire-Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.

    Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
  11. Das Gupta E, Goh EM, Gun SC, Hussein H, Shahril NS, Yeap SS, et al.
    EXCLI J, 2013;12:521-2.
    PMID: 27034635
  12. Shaharir SS, Osman SS, Md Rani SA, Sakthiswary R, Said MSM
    Lupus, 2018 Jan;27(1):25-32.
    PMID: 28467290 DOI: 10.1177/0961203317707062
    Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p 
  13. Kyaw MT, Sakthiswary R, Ani Amelia Z, Rahana AR, Munirah MM
    Cureus, 2020 Apr 11;12(4):e7632.
    PMID: 32399364 DOI: 10.7759/cureus.7632
    BACKGROUND: Methotrexate (MTX), which is the anchor drug in rheumatoid arthritis (RA), targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve. The purpose of this study was to determine the effects of MTX therapy on gonadotropic hormones, i.e. follicular stimulating hormone (FSH) and luteinizing hormone (LH) in female RA patients of reproductive age.

    MATERIALS AND METHODS: This is a cross-sectional study conducted at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC), from January 2018 to July 2018. Women with RA aged between 15 and 49 years who were on MTX therapy for at least six months, were consecutively recruited. All subjects were interviewed to gather information on their menstrual history and menopausal symptoms. The medical records were reviewed to obtain further data on the disease characteristics and RA treatment. The RA disease activity was determined using the DAS 28 scoring system. All subjects were tested for their serum FSH and LH levels.

    RESULTS: A total of 40 patients were included in this study. The median dose of MTX used by the subjects was 12.5 mg weekly. The mean cumulative MTX dose was 1664.92 ± 738.61 mg. More than half (53.1%) of the subjects reported menopausal symptoms especially hot flushes. We found that FSH levels had a significant positive correlation with cumulative MTX dose [(r = 0.86), p < 0.001] and the duration of MTX therapy [(r = 0.84), p < 0.001]. Besides, there was a significant relationship between disease activity based on DAS 28 and FSH levels (p < 0.01). Age, body mass index, disease duration, and weekly MTX dose showed no associations with the FSH levels. On multivariate analysis, DAS 28 was found to be the only parameter that remained significant [β = 1.74 (95% CI 1.17-2.31), p < 0.001]. The LH levels, on the other hand, were not associated with MTX therapy or disease activity.

    CONCLUSION: Higher levels of FSH, which is an indicator of diminished ovarian reserve, have a significant positive relationship with disease activity, cumulative dose, and duration of MTX therapy in RA.

  14. Sakthiswary R, Chuah HY, Chiang KS, Liew YS, Muhammad Aizat NA
    Lupus, 2021 Oct;30(12):1946-1954.
    PMID: 34565208 DOI: 10.1177/09612033211045057
    OBJECTIVE: In the recent months, there have been several case reports and case series on COVID-19 in patients with systemic lupus erythematosus(SLE). We conducted a pooled analysis and systematic review to summarise the findings of these articles. Besides, we aimed to determine the predictors of severe COVID-19 infection in SLE by comparing the mild to moderate cases with the severe to critical ones.

    METHOD: All case reports and case series pertaining to COVID-19 in SLE were retrieved from Pubmed, Wiley Online Library, Springer Link, Science Direct and Web of Science databases using 'lupus', 'systemic lupus erythematosus', 'coronavirus', 'SARS-CoV-2', 'SLE' and "Covid-19" as keywords. The following data were extracted from the selected articles: country, age of the patient and the characteristics of SLE such as disease duration, organ or system involved, baseline medications and the severity of the COVID-19 infection. Data extracted from the articles were utilised to perform the pooled analysis.

    RESULTS: A total of 24 articles with 48 patients met the eligibility criteria. The median age at diagnosis of COVID-19 infection was 41 years (IQR: 11-66 years). The median SLE disease duration prior to the diagnosis of COVID-19 was 9 years (IQR: 0-30 years). A total of 22 (45.83%) patients had severe to critical COVID-19. This pooled data did not demonstrate any difference in the baseline medications between the 2 groups. Patients with lupus nephritis were significantly more prone to develop severe to critical disease (p = 0 .036) with an odds ratio of 5.40 (95% confidence interval of 1.120-26.045).

    CONCLUSION: We found that lupus nephritis was the only predictor of severe to critical COVID-19 in SLE.

  15. Das Gupta E, Sakthiswary R, Lee SL, Wong SF, Hussein H, Gun SC
    Int J Rheum Dis, 2018 Mar;21(3):705-709.
    PMID: 27456670 DOI: 10.1111/1756-185X.12918
    AIM: The main objective of this study is to elucidate the clinical significance of the SLC2A9/GLUT9 rs11722228 polymorphism among male gout patients.
    METHOD: We consecutively recruited all newly diagnosed male gout patients who were treatment-naive from the rheumatology outpatient clinics of two Malaysian hospitals. Age-matched healthy male adults were employed as controls. All subjects were tested for the SLC2A9/GLUT9 rs11722228 genotypes, serum uric acid (SUA), urine uric acid and creatinine levels. All gout subjects were examined for the presence of tophi and sonographically screened for renal calculi.
    RESULTS: A total of 73 male gout patients and 73 age-matched healthy male adults were recruited in this study. The genotypic frequencies of SLC2A9/GLUT9 rs1172228 did not differ significantly between the gout cases and the healthy controls. The gout subjects with the CC genotype had significantly higher SUA levels (P = 0.002), family history of gout (P < 0.050) and the occurrence of renal calculi (P = 0.026). The SUA-adjusted odds ratios (OR) of the occurrence of renal calculi in the CC genotype (OR = 1 [reference]) was significantly higher than the CT genotype (OR = 0.338, 95%CI: 0.141-0.813) and the TT genotype (OR = 0.271, 95%CI: 0.086-0.854).
    CONCLUSIONS: The genotypic distribution of SLC2A9/GLUT9 rs1172228 in male gout patients did not differ significantly from that of healthy male controls. However, the CC genotype in gout had significant associations with higher levels of SUA, renal calculi and a positive family history of gout.
    Study site: Rheumatology clinic, Tuanku Jaafar Hospital, Malaysia and Putrajaya Hospital, Malaysia
  16. Tan LF, Sakthiswary R, Veshaaliini UR, Shaharir SS, Wahab AA, Aziz S, et al.
    J Clin Med, 2023 Jul 17;12(14).
    PMID: 37510831 DOI: 10.3390/jcm12144716
    Immunoglobulin (Ig) G4 accounts for 4-6% of the total IgG in a healthy human. Several evidence-based studies have suggested that the level of IgG4 is significantly elevated in autoimmune diseases, including rheumatoid arthritis (RA). The clinical significance of IgG4 in RA with regard to disease activity, severity, and treatment response remains elusive. We consecutively recruited 174 patients with RA from our rheumatology clinic. All subjects were assessed for their disease activity based on DAS28, radiographic joint damage based on the Modified Sharp Score (MSS), the functional capacity based on the Health Assessment Questionnaire -Disability Index (HAQ-DI), and treatment responsiveness using the European League Against Rheumatism (EULAR) response criteria. The serum IgG4 of the recruited subjects was measured via the ELISA test. The mean serum IgG4 level was 60.23 ± 30.08 mg/dL. We found that serum IgG4 had significant positive correlations with disease activity (r = 0.406; p < 0.001), ESR (r = 0.155; p = 0.041), CRP (r = 0.269; p < 0.001), joint damage (r = 0.195; p = 0.012) and functional disability (r = 0.909; p < 0.001). Subjects with elevated IgG4 (IgG4 > 86 mg/dL) had significantly higher ESR, CRP, HAQ-DI, and DAS 28 and a poorer treatment response compared to the group with non-elevated IgG4. After multivariate analysis, only HAQ-DI (OR = 4.229, 95% CI 1.302, 15.751, p = 0.018) and DAS28 (OR = 3.743, 95% CI 1.062, 13.193, p = 0.040) remained significantly associated with elevated serum IgG4. The preliminary findings of this study could suggest serum IgG4 to be a potential biomarker of disease activity and functional disability in RA.
  17. Sakthiswary R, Uma Veshaaliini R, Chin KY, Das S, Sirasanagandla SR
    Front Med (Lausanne), 2022;9:962969.
    PMID: 36059831 DOI: 10.3389/fmed.2022.962969
    Rheumatoid arthritis (RA) is an autoimmune disease, in which the inflammatory processes involve the skeletal system and there is marked destruction of the bones and the surrounding structures. In this review, we discuss the current concepts of osteoimmunology in RA, which represent the molecular crosstalk between the immune and skeletal systems, resulting in the disruption of bone remodeling. Bone loss in RA can be focal or generalized, leading to secondary osteoporosis. We have summarized the recent studies of bone loss in RA, which focused on the molecular aspects, such as cytokines, autoantibodies, receptor activator of nuclear kappa-β ligand (RANKL) and osteoprotegerin (OPG). Apart from the above molecules, the role of aryl hydrocarbon receptor (Ahr), which is a potential key mediator in this process through the generation of the Th17 cells, is discussed. Hence, this review highlights the key insights into molecular mechanisms of bone loss in RA.
  18. Nordin FZ, Shaharir SS, Mohamed Said MS, Mohd R, Sakthiswary R, Tengku Mohd TAM, et al.
    Lupus, 2024 Nov 07.
    PMID: 39506570 DOI: 10.1177/09612033241297548
    INTRODUCTION: Heterogeneity of the clinical manifestations of systemic lupus erythematosus (SLE) may lead to diagnostic delays. This study is aimed at determining the health-seeking behaviour patterns and factors associated with diagnostic delays in a multi-ethnic SLE cohort in Malaysia.

    METHODOLOGY: This was a cross-sectional study involving SLE patients who visited our institute between January 2020 and June 2021. A review of the medical records and face-to-face interviews were conducted to obtain sociodemographics, SLE disease characteristics and the intervals from the first symptoms to the diagnosis. Health-seeking behaviours were assessed by asking about the patients' first action during the initial symptoms and were divided into: (i) seeking professional health personnel; (ii) self-treatment; and (iii) the use of the internet as a primary source of information. Diagnostic delays were defined as the interval between initial symptoms and SLE diagnosis of more than 6 months. Low-level disease activity state (LLDAS) at 12 months was assessed from the medical records. Univariate and multivariate logistic regression analysis was subsequently conducted to determine factors associated with diagnostic delays.

    RESULTS: Among the 154 patients included in the study, 24% (n = 37) had delayed diagnosis. The delay was significantly higher among the Indian versus Malay versus Chinese (42.9% vs 28% vs 10.8%, p = 0.037). Patients with rash tend to have delayed diagnosis (37.8% vs 22.2%, p = 0.08) while fewer patients with frothy urine had delayed diagnosis (8.1% vs 21.4%, p = 0.09). No significant association was found between health-seeking behaviours and diagnostic delays. The rate of LLDAS at 12 months was significantly lower among patients with delayed diagnosis (43.2% vs 70.0%, p = 0.006). Chinese ethnicity remained the only significant factor associated with lesser diagnostic delays in the multivariate analysis, with OR 0.30 (CI 0.09-0.93), p = 0.037.

    CONCLUSION: There were ethnic disparities in the early diagnosis of SLE in Malaysia, with Indian patients having a longer interval between the first symptom and diagnosis while the Chinese were associated with lower diagnostic delays. Early diagnosis predicted early attainment of LLDAS, suggesting that prompt recognition of the initial SLE symptoms is important.

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