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Fulltext ANA negative (Ro) lupus erythematosus with multiple major organ involvement: a case report

Che Maraina CH, Kamaliah MD, Ishak M

Asian Pac J Allergy Immunol, 2002 Dec;20(4):279-82.
PMID: 12744629

Anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) occurs in about 4-13% of SLE cases. A small group of ANA negative SLE patients with positive anti-Ro antibodies usually present with typical vasculitic skin lesions which can be associated with photosensitivity, renal disease, congenital heart block or neonatal lupus. We present a case of a persistently ANA negative patient who presented with joint pain, rashes, mouth ulcer and alopecia. Clinical diagnosis of systemic lupus erythematosus was made even though ANA was negative. She was started on steroids and went into remission. Later, she developed several episodes of convulsions associated with fever and prominent vasculitic lesions. The patient was also found to have microscopic hematuria, proteinuria, anemia and thrombocytopenia. Renal biopsy showed lupus nephritis class 1B. Due to the prominent skin lesions, we performed anti-extractable nuclear antigens (ENA) antibodies test and anti-Ro turned out to be positive. The final diagnosis was ANA negative SLE (Ro lupus) with cutaneous, renal, musculoskeletal, hematological and cerebral Involvement.
IL-23/IL-17 axis in the pathogenesis and treatment of systemic lupus erythematosus and rheumatoid arthritis

Farah Izati A, Wong KK, Che Maraina CH

Malays J Pathol, 2020 Dec;42(3):333-347.
PMID: 33361714

Interleukin-23 (IL-23) and IL-17 are the gatekeepers of CD4+ T helper 17 (Th17) cells where IL-23 is required for the development and expansion of Th17 cells that subsequently produce IL-17 to promote inflammation. Owing to such pro-inflammatory properties, the IL-23/IL-17 axis has emerged as an important mechanism in the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In recent years, therapeutic antibodies targeting IL-23 (e.g. ustekinumab, tildrakizumab, guselkumab) or IL-17 (e.g. brodalumab, secukinumab, ixekizumab) have been approved for the treatment of various autoimmune diseases. In this review, we describe the pathogenic mechanisms of IL-23/IL-17 axis in SLE and RA, as well as summarising the findings from phase II and III clinical trials of anti-IL-23/IL-17 therapeutic antibodies in SLE and RA patients. In particular, phase II study has demonstrated that the anti-IL-23 antibody (ustekinumab) confers enhanced treatment outcomes in SLE patients, while anti-IL-17 antibodies (secukinumab and ixekizumab) have shown improved clinical benefits for RA patients in phase II/III studies. Our review highlights the emerging importance of targeting the IL-23/IL-17 axis in SLE and RA patients.
Anti-nucleosome antibodies as a disease activity marker in patients with systemic lupus erythematosus

Suleiman S, Kamaliah D, Nadeem A, Naing NN, Che Maraina CH

Int J Rheum Dis, 2009 Jul;12(2):100-6.
PMID: 20374326 DOI: 10.1111/j.1756-185X.2009.01391.x

AIM: To measure the level of anti-nucleosome antibodies in systemic lupus erythematosus (SLE) patients, to determine the sensitivity and the specificity of these antibodies in the diagnosis of the disease and to evaluate the relationship between the levels of anti-nucleosome antibodies, anti-dsDNA (double-stranded DNA) and SLE disease activity.
METHODS: A cross-sectional study was conducted. All patients attended either a medical specialist clinic or were admitted to the medical wards of Hospital Universiti Sains Malaysia with the diagnosis of SLE (n = 90), other connective tissue diseases (n = 45) or were normal controls (n = 90) within the period from July 2004 until September 2005. They were tested for anti-nucleosome antibodies by enzyme-linked immunosorbent assay and anti-DNA antibodies by immunofluorescence. SLE disease activity was evaluated by SLE disease activity index (SLEDAI) score.
RESULTS: Out of 90 SLE patients, anti-nucleosome antibodies were positive in 47 (52.2%) patients, whereas these antibodies were positive in three (6.7%) patients with other connective tissue diseases. Anti-dsDNA antibodies were positive in 33 (36.7%) SLE patients, whereas these antibodies were positive in four (8.9%) patients with other connective tissue diseases. Anti-nucleosome antibodies were positive in 40 (97.6%) patients with active SLE, whereas these antibodies were positive in seven (14.3%) patients with inactive SLE. Anti-nucleosome antibodies had a stronger correlation than anti-dsDNA antibodies with SLEDAI score. There was a significant association between anti-nucleosome antibodies and disease activity.
CONCLUSION: Anti-nucleosome antibodies test is highly sensitive and specific for the diagnosis of SLE, especially when the anti-dsDNA antibodies are absent. They are additional disease activity markers in the assessment of SLE disease activity.
Tear cytokine levels in allergic rhinitis without ocular symptoms

Tai ELM, Loong LJ, Madhusudhan P, Ramli RR, Che Maraina CH, Hussein A

Can J Ophthalmol, 2019 10;54(5):635-639.
PMID: 31564357 DOI: 10.1016/j.jcjo.2018.12.003

OBJECTIVE: To compare cytokine levels in the pre-corneal tear film between patients with allergic rhinitis, allergic rhinoconjunctivitis and the normal population.
DESIGN: A comparative cross sectional study.
PARTICIPANTS: Patients were divided into Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal population).
METHODS: A comparative cross-sectional study was conducted. Patients were divided into; Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal controls). Tears were collected using Schirmer strips and cytokine analysis performed using enzyme linked immunosorbent assay.
RESULTS: There were a total of 68 subjects. Median values of cytokines in the allergic rhinitis group were as follows; TNFa (45.34 pg/ml), IL-4 (61.91 pg/ml), IL-5 (8.92 pg/ml), IL-6 (538.37 pg/ml) and IL-8 (1438.72 pg/ml). Cytokine levels in the group with allergic rhinoconjunctivitis were approximately two-fold higher than in the group with allergic rhinitis only. The median cytokine level in the control group was lowest. A significant inter-group difference was observed for TNF-alpha, IL-4, IL-6 and IL-8 levels, with allergic rhinoconjunctivitis patients demonstrating significantly elevated cytokines compared to those with allergic rhinitis only (p<0.001). These four cytokines were also significantly higher in those with allergic rhinitis than in controls (p<0.005). Although the group with allergic rhinoconjunctivitis had the highest levels of IL-5, no statistically significant inter-group difference was noted (p=0.479).
CONCLUSION: This study demonstrated the presence of raised tear film inflammatory cytokines even in allergic rhinitis patients without ocular symptoms. These patients may be at increased risk of developing allergic conjunctivitis. These findings not only substantiate the immunological theory of the naso-ocular reflex, but have clinical and therapeutic implications for the holistic management of allergic rhinitis and conjunctivitis.
Fulltext Association of anti-CLIC2 and anti-HMGB1 autoantibodies with higher disease activity in systemic lupus erythematosus patients

Syahidatulamali CS, Wan Syamimee WG, Azwany YN, Wong KK, Che Maraina CH

J Postgrad Med, 2017 9 2;63(4):257-261.
PMID: 28862243 DOI: 10.4103/jpgm.JPGM_499_16

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by numerous autoantibodies. In this study, we investigated the presence of anti-chloride intracellular channel 2 (anti-CLIC2) and anti-high mobility group box 1 (anti-HMGB1) autoantibodies in SLE patients (n = 43) versus healthy controls ([HCs] n = 43), and their association with serological parameters (antinuclear antibody [ANA], anti-double-stranded DNA [anti-dsDNA], and C-reactive protein [CRP]) and disease activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (active or inactive).
SETTINGS AND DESIGN: Case-control study at Rheumatology Clinic of Universiti Sains Malaysia Hospital.
SUBJECTS AND METHODS: The sera of SLE patients and HCs were tested for the presence of anti-CLIC2 and anti-HMGB1 autoantibodies using human recombinant proteins and ELISA methodologies. Other serological parameters were evaluated according to routine procedures, and patients' demographic and clinical data were obtained.
STATISTICAL ANALYSIS: Mann-Whitney U-test, Chi-square test, Fisher's exact test, and receiver operating characteristic analysis.
RESULTS: Anti-CLIC2 autoantibody levels were significantly higher in SLE patients compared to HCs (P = 0.0035), whereas anti-HMGB1 autoantibody levels were not significantly elevated (P = 0.7702). Anti-CLIC2 and anti-HMGB1 autoantibody levels were not associated with ANA pattern, anti-dsDNA, and CRP. Interestingly, SLEDAI score (≥6) was associated with anti-CLIC2 (P = 0.0046) and with anti-HMGB1 (P = 0.0091) autoantibody levels.
CONCLUSION: Our findings support the potential of using anti-CLIC2 autoantibodies as a novel biomarker for SLE patients. Both anti-CLIC2 and anti-HMGB1 autoantibody levels demonstrated potential in monitoring SLE disease activity.
Fulltext Comparison of catalase, glutathione peroxidase and malondialdehyde levels in tears among diabetic patients with and without diabetic retinopathy

Kwong-Han K, Zunaina E, Hanizasurana H, Che-Badariah AA, Che-Maraina CH

J Diabetes Metab Disord, 2022 Jun;21(1):681-688.
PMID: 35673514 DOI: 10.1007/s40200-022-01030-2

BACKGROUND: Various studies suggest that oxidative stress has a role in the etiology of diabetes mellitus (DM) and its complications. Detection of antioxidant enzymes and malondialdehyde (MDA) level in ocular fluid may provide the possible biomarkers for monitoring the progression of diabetic retinopathy (DR). The aim of this study was to compare catalase, glutathione peroxidase (GPx) and MDA levels in tears among diabetic patients with and without DR.
METHODS: A cross-sectional study was conducted among type 2 DM patients. The patients were divided into three groups: no DR, non-proliferative DR (NPDR) and proliferative DR (PDR). Tears samples were collected using Schirmer strips for measurement of catalase, GPx and MDA.
RESULTS: A total of 171 patients were recruited in this study (no DR, 58 patients; NPDR, 57 patients; PDR, 56 patients). There was significant difference in the mean level of GPx in tears between the three groups (no DR, 658.08 ± 115.70 U/L; NPDR, 653.78 ± 87.90 U/L; PDR, 605.31 ± 107.47 U/L, respectively) before and after adjustment for covariates (p = 0.013 and p = 0.001, respectively). Bonferroni post-hoc analysis showed PDR group had significantly lower mean GPx level than in no DR (p=0.001) and NPDR (p=0.037) after adjustment for covariates. There was no significant difference of mean catalase and MDA in the tears between the three groups before and after adjustment for covariates.
CONCLUSION: This study demonstrated that diabetic patient with DR is associated with low level of GPx in tears, suggesting that this antioxidant enzyme is a potential biomarker for predicting the presence of DR.