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  1. Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, et al.
    Arthritis Res Ther, 2016 11 09;18(1):260.
    PMID: 27829463 DOI: 10.1186/s13075-016-1163-2
    BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE.
    METHODS: Data were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS.
    RESULTS: Of the 1846 patients assessed, criteria for LLDAS were met by 44 %. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95 % CI 0.19-0.49, p 
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  2. Gangaram HB, Kong NCT, Phang KS, Suraiya H
    Med J Malaysia, 2004 Dec;59(5):638-48.
    PMID: 15889567
    The usefulness of the direct immunofluorescent antibody technique--lupus band test--for the diagnosis of systemic lupus erythematosus (SLE) has been well established. The aims of the study were to determine the prevalence of the LBT at various sites of the skin in a cross section of patients with SLE and its correlation with disease activity. The LBT was demonstrated in 64% of skin lesions, 63% in non-lesional sun-exposed (NLSE) skin and 25% in non-lesional sun-protected (NLSP) skin. The prevalence of the LBT in lesional and NLSE groups was significantly different from the NLSP group (p = 0.03 and 0.005 respectively). There was a significant correlation between the presence of a positive LBT in NLSE skin with the presence of the LE cell phenomenon (p = 0.04) and anti - ds DNA antibody (0.02). In addition, there was a significant correlation between IgG LBT in the NLSE skin with serum hypocomplementaemia (p = 0.03) and anti - ds DNA antibody (p = 0.04). Other than these, no significant correlation was detected between the LBT from the 3 sites with overall clinical activity, renal disease, active skin lesions, or other laboratory indices of activity. These findings suggest that the LBT is mainly indicated as a diagnostic tool and has little role in assessing disease activity.
    Study site: Wards and clinics of the General Hospital, Kuala Lumpur, Malaysia
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  3. Cheong SK, Chin SF, Kong NC
    Malays J Pathol, 1997 Dec;19(2):121-5.
    PMID: 10879252
    Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by increased B cell activity and depressed T cell function. However, the contribution of the immunoregulatory system to its pathogenesis is still unclear. The recent development in the production of monoclonal antibodies and the availability of bench-top flow cytometers have allowed rapid quantitation of peripheral blood lymphocyte subsets. We analysed the distribution of the lymphocyte subsets in 24 patients with active SLE and 18 with inactive SLE. The distribution of immunoregulatory cells in 72 normal volunteers was used as control. Statistical analysis showed that there were significant differences between both the SLE groups and the normal controls, for total lymphocytes, T cells, B cells, T helper cells, T suppressor cells, T helper/suppressor ratio and natural killer cells. There was a significant difference for T helper cells between active and inactive SLE. T helper cells levels were found to be low in inactive SLE and lower in active SLE. It appears that treatment-induced remissions did not restore the levels of immunoregulatory cells to normal. Thus, T helper cell levels reflect disease activity and longitudinal assays of T helper cells may serve as an indicator of disease reactivation.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  4. Wang F, Looi LM
    Q. J. Med., 1984;53(210):209-26.
    PMID: 6463196 DOI: 10.1093/oxfordjournals.qjmed.a067794
    Thirty-one patients with systemic lupus erythematosus had membranous lupus nephropathy (MLN). They were divided into two groups. Group I consisted of 13 patients who had pure MLN but the patients in Group 2 had segmental proliferation in up to 35 per cent of their glomeruli. The rest of the glomeruli had purely membranous change. The patients of Group 2 were no different from the other MLN patients in terms of age, sex and race. The extrarenal disease in both groups was extensive and severe. The renal disease was usually associated with the nephrotic syndrome or oedema but was asymptomatic throughout in one patient. Both renal and extrarenal features responded to treatment initially but relapses were frequent and often severe. Relapses often occurred as treatment was discontinued or medication reduced. Survival at six years in Group I was 62 per cent and in Group 2 was 50 per cent. Only one patient died with renal failure although five patients had impaired renal function at death. The chief causes of death were disease of the central nervous system and infection.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  5. Goh SW, Jamil A, Nor NM, Cader RA, Shaharir SS
    Indian J Dermatol Venereol Leprol, 2019 12 12;86(1):68-70.
    PMID: 31823905 DOI: 10.4103/ijdvl.IJDVL_961_18
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  6. Fernandez SH
    Malays J Pathol, 2000 Jun;22(1):25-9.
    PMID: 16329534
    A 26-year-old Indian lady was admitted for lower abdominal pain, diarrhoea, vomiting, fever and cough. The initial diagnosis was that of peritonitis secondary to ruptured or perforated viscus with lobar pneumonia. On laparotomy, she was found to have necrotizing or Kikuchi's lymphadenitis of the abdominal lymph nodes. The initial two antinuclear antibody (ANA) results came back negative. She was diagnosed to have systemic lupus erythematosus (SLE) when the third sample for ANA came back positive and the double-stranded DNA (dsDNA) antibody test was homogenously positive. This case illustrates a need to be aware that necrotizing lymphadenitis can precede the onset of systemic lupus erythematosus.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  7. Sun C, Molineros JE, Looger LL, Zhou XJ, Kim K, Okada Y, et al.
    Nat Genet, 2016 Mar;48(3):323-30.
    PMID: 26808113 DOI: 10.1038/ng.3496
    Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  8. Raymond AA, Zariah AA, Samad SA, Chin CN, Kong NC
    Lupus, 1996 Apr;5(2):123-8.
    PMID: 8743125 DOI: 10.1177/096120339600500207
    Cerebral lupus (CL) is a common cause of morbidity and mortality in patients with SLE. The brain CTs of 27 consecutive adult patients with SLE and various neurological presentations were reviewed. The median age and duration of neurological symptoms at the time of the brain CT were 30 years (range = 14-51 years) and six days (range = 1 day-22 years), respectively. Eleven patients (41%) had normal CTs. The abnormalities in the remaining patients could be divided into six categories: (a) cerebral atrophy alone (two patients); (b) calcification alone (three patients); (c) infarct(s) alone (five patients); (d) cerebral atrophy and calcification (three patients); (e) cerebral atrophy and infarct(s) (one patient) and (f) cerebral atrophy, calcification and infarct(s) (two patients). Altogether eight patients (30%) (age range = 17-47 years) had intracerebral calcification: the globus pallidus was involved in all, putamen in two, head of the caudate nucleus in one, thalamus in one, centrum semiovale in two and cerebellum in three patients. Two patients had extensive calcifications of most of the basal ganglia, centrum semiovale and cerebellum. There was no relationship between the presence/degree of calcification and age of patients/duration or type of neurological presentation. The pathogenesis of cerebral calcification in CL is unknown. Cerebral lupus must now be included in the differential diagnosis of intracerebral calcification.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  9. Prathap K, Looi LM
    Ann Acad Med Singap, 1982 Jan;11(1):52-6.
    PMID: 7073229
    Adequately biopsied renal tissue received in the Department of Pathology, University Hospital, Kuala Lumpur from 1,000 consecutive Malaysian patients during an eleven year period between 1970 and 1981 was reviewed. The youngest patient was 6 days old and the oldest 80 years. Both sexes were equally represented. The majority of the patients were Chinese (71%) with Malays and Indians comprising most of the remainder. Over half the patients (50.4%) presented with the nephrotic syndrome. Other modes of presentation included systemic lupus erythematosus, proteinuria and haematuria separately or in combination and hypertension. Minimal change (25.7%) and proliferative glomerulonephritis (24.8%) were present in about equal numbers and together accounted for over half of the cases (50.5%). Lupus nephritis was the third most common diagnosis (18.4%). In addition, there were patients with focal glomerulonephritis (5.4%), membranous glomerulonephritis (5.5%), Berger's disease (5.8%), amyloidosis (0.6%) and end stage renal disease (4.0%).
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  10. Ghazali WSW, Daud SMM, Mohammad N, Wong KK
    Medicine (Baltimore), 2018 Oct;97(42):e12787.
    PMID: 30334968 DOI: 10.1097/MD.0000000000012787
    The aims of this study were to determine damage index in systemic lupus erythematosus (SLE) patients based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) and to determine the laboratory and clinico-demographic factors affecting SDI.This is a retrospective cohort study of 94 SLE patients attending rheumatology clinics in 2 local hospitals in Kelantan, Malaysia. The patients were divided into 2 groups based on SDI score assigned by the attending physician, 0 (without damage) or ≥1 (with damage). Newly diagnosed SLE patients with disease duration less than 6 months were excluded.A total of 45 (47.9%) SLE patients showed damage by SDI score. Majority of the subjects had neuropsychiatric damages (21/94; 22.3%) followed by skin (12/94; 12.8%) and musculoskeletal (6/94; 6.4%) damage. SDI score was significantly associated with higher disease duration (6.2 ± 6.57 years vs 4.5 ± 3.7 years; P = .018), lower prednisolone dose (8.74 ± 10.89 mg vs 4.89 ± 3.81 mg; P 
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  11. Lim SC, Chan EWL, Tang SP
    Lupus, 2020 Aug;29(9):1106-1114.
    PMID: 32631203 DOI: 10.1177/0961203320939185
    BACKGROUND: Paediatric systemic lupus erythematosus is a rare autoimmune disease with a wide spectrum of clinical presentation in different populations. We present a cohort of paediatric systemic lupus erythematosus in Malaysia where the disease features and outcomes are still largely unknown.

    METHODS: A retrospective review of all paediatric systemic lupus erythematosus patients with at least 6 months follow-up at Selayang Hospital from 2004 to 2016. Epidemiological, clinical and outcome data were collected and analysed.

    RESULTS: A total of 141 paediatric systemic lupus erythematosus patients, 87.9% females, were followed up for a median 6.3 years (interquartile range 3.6-9.0). The median age at diagnosis was 10.8 years (interquartile range 9.0-12.0 years), positive family history of systemic lupus erythematosus was present in 12.1% and the majority (61.7%) were of Malay ethnicity. Common presentations included fever (87.2%), vasculitic rash (72.3%) and lethargy (69.5%). At diagnosis, leukopenia (51.1%), thrombocytopenia (41.8%) and cutaneous lupus (56%) predominate with significant renal involvement (39.7%). Renal (45.4%), liver (26%) and the central nervous system (17%) were important major organs involved during the course of the disease. At diagnosis, almost all (99.3%) patients had high disease activity (mean Systemic Lupus Erythematosus Disease Activity Index score 20.1 ± 9.6). The majority (62.4%) achieved remission or low disease activity after 6 months, maintained over the next 10 years. Damage occurred early (39.1% at 1 year) and increased with time. Ocular damage was the most common side effect (29%) and was predominantly corticosteroid related (93%). Growth retardation was significant (38.2%) with no gonadal failure or secondary malignancies. End-stage renal disease occurred in 3.1% patients whereas 53.1% had sustained renal remission. Overall mortality was 1.4%.

    CONCLUSION: Despite high disease activity at diagnosis, the majority had good sustained response to treatment with low overall mortality. However, there was progressive accrual of organ damage, highlighting the need for further research and refinements into therapies for paediatric systemic lupus erythematosus.

    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  12. Cheah CK, Ramanujam S, Mohd Noor N, Gandhi C, D Souza BA, Gun SC
    Lupus, 2016 Feb;25(2):214-6.
    PMID: 26377236 DOI: 10.1177/0961203315606441
    Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  13. Cader RA, Mei Yee AK, Yassin A, Ahmad I, Haron SN
    Asian Pac J Cancer Prev, 2018 Dec 25;19(12):3551-3555.
    PMID: 30583682
    Background: Malignancies are among the leading causes of death in Systemic Lupus Erythematosus (SLE)
    patients with studies reporting a higher prevalence of malignancy in SLE patients compared to the general population.
    We wanted to determine the frequency of cancer in a cohort of SLE patients and identify its associated risk factors.
    Methods: Cross-sectional study involving SLE patients attending the nephrology outpatient clinic, Universiti
    Kebangsaan Malaysia Medical Centre between January and June 2014. Results: We recruited 228 patients (207 female,
    21 male), aged 40.48 ± 12.86 years with mean SLE duration of 11.65 ± 6.46 years. Majority (87%) had lupus nephritis
    and were in remission with a median SLEDAI score 2 (0, 14). Majority (89%) were on corticosteroid with either a
    steroid sparing agent like mycophenolate mofetil (15.4%), azathioprine (36.8%) or ciclosporin (15.4%). One hundred
    and sixty (70.2%) patients were either receiving or had received intravenous cyclophosphamide with median dose
    of 5,173.6 ± 3,242.4 mg. Seven female patients were diagnosed with cancer during the course of their SLE with 56
    (34-78) years being median age at malignancy and SLE duration of 4 (0-12) years. Majority (5/7) had lupus nephritis
    and all patients a median dose of prednisolone 10 (2.5, 10) mg with 10 (4-24) years of steroids. Two patients had a
    family history of cancer with majority developing cancer after the diagnosis of SLE. Two patients received intravenous
    cyclophosphamide prior to the development of cancer for their SLE compared to overall cohort of 160. Three patients
    had colorectal cancer, 2 had cervical cancer, 1 had breast cancer, and one patient had germ cell tumour and one thyroid
    cancer. All patients had their cancer successful treated with no signs of recurrence. Conclusion: We found a lower
    occurrence of cancer in our SLE patients as compared with the reported literature.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*
  14. 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/pathology
  15. Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.
    Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
    PMID: 24608226 DOI: 10.1093/hmg/ddu106
    Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
  16. Cheng LE, Amoura Z, Cheah B, Hiepe F, Sullivan BA, Zhou L, et al.
    Arthritis Rheumatol, 2018 07;70(7):1071-1076.
    PMID: 29513931 DOI: 10.1002/art.40479
    OBJECTIVE: To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.

    METHODS: In this phase Ib, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1-letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

    RESULTS: The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4-point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (-36.3% versus -24.7%) and the SLEDAI score (-47.8% versus -10.7%) and in tender (-22.8% versus -13.5%) and swollen (-62.1% versus -7.8%) joint counts on day 169.

    CONCLUSION: AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.

    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology
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