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HLA-DRB genes and antiribosomal P antibodies in systemic lupus erythematosus

Teh LS, Doherty DG, Williams BD

Br J Rheumatol, 1994 Dec;33(12):1125-6.
PMID: 8000739

Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese.

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Prevalence and clinical significance of antibodies to ribonucleoproteins in systemic lupus erythematosus in Malaysia

Wang CL, Ooi L, Wang F

Br J Rheumatol, 1996 Feb;35(2):129-32.
PMID: 8612023

One hundred and seventy patients with systemic lupus erythematosus (SLE) were studied for the prevalence of antibodies to the small RNA-associated proteins Ro/SSA, La/SSB, Sm, U1RNP and Sm. The relationship of these autoantibodies to different races, sexes and clinical manifestations of SLE was evaluated. Passive immunodiffusion was employed using human spleen extract as antigen source for Ro and rabbit thymus extract for La, Sm and U1RNP. We found the prevalence of antibodies to be as follows: anti-Ro/SSA, 36%; anti-La/SSB, 8%; anti-Sm, 15% ; anti-U1RNP, 21%. Except for a low prevalence of anti-La, the prevalence of these antibodies was similar to that in Western studies, The prevalence of anti-Ro/SSA is similar to that reported in the Western studies, but lower than that reported in the Oriental patients from Singapore and Hong Kong. Linkages of anti-Ro with anti-La antibodies were usual; however, although anti-Sm antibodies were usually associated with anti-U1RNP, they were more frequently associated with anti-Ro antibodies. The Malay patients had a high prevalence of anti U1RNP compared to other races. No gender difference was detected. Anti-Sm antibody was associated with serositis and anti-U1RNP antibodies with Raynaud's phenomenon. No association was found between the presence of skin renal or cerebral manifestations and any specific antibodies or combination of antibodies.

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Frequency and role of low molecular weight IgM in systemic lupus erythematosus. Study of patients from different ethnic origins

Roberts-Thomson PJ, Shepherd K, Bradley J, Boey ML

Rheumatol Int, 1990;10(3):95-8.
PMID: 2392640

Low molecular weight IgM (LMW IgM) is the monomeric subunit of the naturally occurring pentameric IgM. It is not seen in health but has been previously observed in systemic lupus erythematosus (SLE) particularly in those patients with active disease and may reflect an adverse prognostic finding. We have therefore studied the presence of LMW IgM in 33 Chinese or Malay SLE patients (Singapore) and 21 Caucasian patients (Adelaide). LMW IgM was measured using filtration chromatography or by a sensitive immunoblotting technique. LMW IgM was observed in all patients in the Adelaide group and in 32 patients in the Singapore group with slightly greater quantities being seen in the Adelaide group. LMW IgM constituted up to 15.3% of the total IgM and was frequently associated with the presence of other low molecular weight IgM oligomers. In both groups LMW IgM correlated significantly with the total IgM levels (P less than 0.01). In a more detailed study in the Singapore group LMW IgM also correlated significantly with the IgM anticardiolipin levels (P = 0.02) but not with IgG anticardiolipin or with IgG or IgM anti-DNA levels or with rheumatoid factor. Patients with more extensive organ involvement had higher levels of LMW IgM but not at a significant level. We conclude that circulating LMW IgM occurs almost universally in SLE, is closely related to the total IgM levels and appears independent of ethnic background. The significance of LMW IgM in this disorder is unclear.

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Paediatric rheumatology clinic population in Southeast Asia: are we different?

Arkachaisri T, Tang SP, Daengsuwan T, Phongsamart G, Vilaiyuk S, Charuvanij S, et al.

Rheumatology (Oxford), 2017 03 01;56(3):390-398.
PMID: 27994096 DOI: 10.1093/rheumatology/kew446

Objectives: To examine the descriptive epidemiology of the patient population referred to paediatric rheumatology centres (PRCs) in Southeast Asia (SEA) and to compare the frequency of conditions encountered with other PRC populations.

Methods: A web-based Registry for Childhood Onset Paediatric Rheumatic Diseases was established in 2009 and seven PRCs in four SEA countries, where paediatric rheumatologists are available, participated in a prospective 24 month data collection (43 months for Singapore).

Results: The number of patients analysed was 4038 (788 from Malaysia, 711 from the Philippines, 1943 from Singapore and 596 from Thailand). Over 70% of patients evaluated in PRCs in Malaysia, the Philippines and Thailand had rheumatic diseases (RDs), as compared with one-half of the proportion seen in Singaporean PRCs, which was similar to the Western PRC experience. Among RDs diagnosed (n = 2602), JIA was the most common disease encountered in Malaysia (41%) and Thailand (61%) as compared with systemic vasculitides in the Philippines (37%) and Singapore (35%) among which Henoch-Schönlein purpura was the most prevalent. SLE and related diseases were more common, but idiopathic pain syndrome and abnormal immunological laboratory tests were rarer than those seen in the West. JIA subtype distributions were different among countries. Among non-RDs (n = 1436), orthopaedic and related conditions predominated (21.7-59.4%).

Conclusion: The frequencies of RDs seen by SEA PRCs were different from those in the West. Systemic vasculitides and SLE were common in addition to JIA. Paediatric rheumatologist availability and healthcare accessibility partially explain these observed discrepancies.

Study site: multination + Selayang Hospital, Malaysia

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology*
Work disability in a multi-ethnic Malaysian systemic lupus erythematosus cohort: A cross-sectional study

Abu Bakar F, Shaharir SS, Mohd R, Kamaruzaman L, Mohamed Said MS

Int J Rheum Dis, 2019 Jun;22(6):1002-1007.
PMID: 30968556 DOI: 10.1111/1756-185X.13572

AIM: To determine the prevalence of work disability (WD) among patients with systemic lupus erythematosus (SLE) and its associated factors.
METHOD: This was a cross-sectional study involving SLE patients aged 18-56 years from Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Employment history was obtained from clinical interviews. WD was defined as unemployment, interruption of employment or premature cessation of employment due to SLE at any time after the diagnosis. SLE disease characteristics, presence of organ damage and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SLEDAI) flare index were determined from the medical records. Self-reported quality of life (QoL) was performed using the Medical Outcomes Study Short Form-36 (SF-36). Demographic factors, disease characteristics, and QoL were compared between patients with and without WD using statistical analyses.
RESULTS: A total of 215 patients were recruited and the majority were Malay (60.5%), followed by Chinese (33.5%), Indian (4.5%) and others (n = 4, 1.9%). The prevalence of WD was 43.2% (n = 93) with 22.3% (n = 48) patients were unemployed at the time of study. Over half the patients with WD (n = 51, 54.8%) had onset of disability at <5 years from diagnosis. Patients with WD had significantly lower health-related QoL. The independent factors associated with WD were SLEDAI score at diagnosis, frequency of flare, Systemic Lupus International Collaborating Clinics score, being married, had lower education and lupus nephritis.
CONCLUSION: We found a high rate of WD in patients with SLE and it was significantly associated with SLE-related factors, in particular higher disease activity, presence of renal involvement and organ damage.

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Fulltext Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci

Molineros JE, Yang W, Zhou XJ, Sun C, Okada Y, Zhang H, et al.

Hum Mol Genet, 2017 03 15;26(6):1205-1216.
PMID: 28108556 DOI: 10.1093/hmg/ddx026

We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci. All five loci passed genome-wide significance: MYNN (rs10936599, Pmeta = 1.92 × 10-13, OR = 1.14), ATG16L2 (rs11235604, Pmeta = 8.87 × 10 -12, OR = 0.78), CCL22 (rs223881, Pmeta = 5.87 × 10-16, OR = 0.87), ANKS1A (rs2762340, Pmeta = 4.93 × 10-15, OR = 0.87) and RNASEH2C (rs1308020, Pmeta = 2.96 × 10-19, OR = 0.84) and co-located with annotated gene regulatory elements. The novel loci share genetic signatures with other reported SLE loci, including effects on gene expression, transcription factor binding, and epigenetic characteristics. Most (56%) of the correlated (r2 > 0.8) SNPs from the 82 SLE loci were implicated in differential expression (9.81 × 10-198

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
Fulltext Damage in the multiethnic Malaysian systemic lupus erythematosus (SLE) cohort: Comparison with other cohorts worldwide

Shaharir SS, Hussein H, Rajalingham S, Mohamed Said MS, Abdul Gafor AH, Mohd R, et al.

PLoS One, 2016;11(11):e0166270.
PMID: 27846298 DOI: 10.1371/journal.pone.0166270

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients.

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology
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: Lupus Erythematosus, Systemic/epidemiology
Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort

Shaharir SS, Gafor AH, Said MS, Kong NC

Int J Rheum Dis, 2015 Jun;18(5):541-7.
PMID: 25294584 DOI: 10.1111/1756-185X.12474

OBJECTIVE:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE.

METHODOLOGY:
A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM.

RESULTS:
Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05).

CONCLUSION:
The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM.

© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

KEYWORDS:
SLE drug treatment; clinical aspects; systemic lupus erythematous

Matched MeSH terms: Lupus Erythematosus, Systemic/epidemiology