Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetic factors strongly influence susceptibility. Cytokines such as the interferon-gamma (IFNG) gene play a key role in controlling the immunity and inflammation, and therefore their polymorphisms may affect these genes' expression levels among individuals. We investigated the frequency of IFNG gene intron (+874) polymorphism, previously reported to be associated with IFNG production, in SLE patients compared to a control group. This population-based case-control study includes 154 SLE patients and 154 healthy control subjects with similar ethnic backgrounds. The genotyping was determined by polymerase chain reaction sequence-specific primer method and using the Chi-squared test for analyzing the association between this single-nucleotide polymorphism and SLE. The allele frequencies of the IFNG (+874) gene polymorphism were not significantly different between SLE patients and control subjects (72.7 vs 77%). However, there was a significant association between A dominance model of inheritance with arthritis (odds ratio = 7.64, 95% confidence interval = 1.56-41.64, P = 0.006, P(c) = 0.03). The result suggested that the +874 intron polymorphism of IFNG can be used as the marker for SLE susceptibility with arthritis in the Thai population.

Predictors of renal involvement in patients with systemic lupus erythematosus.

From a cohort of 109 patients (105 females and 4 males) treated for systemic lupus erythematosus (SLE), 20 patients (18.3%) developed new episodes of lupus nephritis and 89 patients (81.7%) remained free of renal involvement during the follow-up period. The mean duration of follow up was 39.1 +/- 54.4 months. Clinical characteristics associated with developing lupus nephritis were a high systolic blood pressure (> or = 130 mmHg), photosensitivity, cutaneous vasculitis and gastrointestinal (GI) symptoms. Laboratory abnormalities associated with the development of lupus nephritis were hemoglobin < 10 mg/dl, hematocrit < 30%, blood urea nitrogen > 12 mg/dl, serum creatinine > 1.3 mg/dl, ESR > 60, the third component of complement (C3) level < 0.45 and positive antidsDNA antibody. After a multivariable analysis, only high systolic blood pressure, cutaneous vasculitis, hemoglobin < 10 mg/dl and serum creatinine > 1.3 mg/dl remained as statistically significant risk factors for developing lupus nephritis.

A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience.

OBJECTIVE: The optimal treatment of relapse or resistant lupus nephritis (LN) is still unclear. Mycophenolate might be an alternative therapy to avoid toxicities of cyclophosphamide (CYC). This study was aimed to compare enteric-coated mycophenolate sodium (EC-MPS) versus intravenous CYC as an induction therapy. METHODS: The study was a 12-month period of multicentre, open-labelled randomised controlled trial. Fifty-nine patients who had relapsed (36%) or who were resistant to previous CYC treatment (64%) and all who were biopsy-proven class III/IV, were randomised into CYC (n=32) and EC-MPS groups (n=27). The CYC group received intravenous CYC 0.5-1 g/m(2) monthly and the EC-MPS group was treated with EC-MPS 1440 mg/day for first 6 months. After induction therapy, both groups received EC-MPS 720 mg/day until the end of study at 12 months. RESULTS: The study was prematurely terminated due to high rate of serious adverse events in CYC arm. Death and serious infections were observed more in the CYC group (15.6% in CYC and 3.5% in EC-MPS; p=0.04). The early discontinuation rates, mainly from serious infections, were significantly higher in CYC group (percentage differences of 16.9; 95% CI 1.3 to 32.4). At the 12th month, both arms were comparable in terms of complete and partial remission rates (68% CYC and 71% EC-MPS) and times to remission (96 days CYC and 97 days EC-MPS). Composites of unfavourable outcomes (death, doubling of serum creatinine, non-remission and intolerance to treatment) were 46.9% and 37% in CYC and EC-MPS (risk difference=9.84; p=0.44). CONCLUSIONS: EC-MPS may have comparable efficacy, but was better tolerated than CYC. EC-MPS should be an alternative choice of treatment for difficult-to-treat LN, particularly in CYC-experienced LN patients. Due to an early termination of the study, further clinical implementation could be cautiously used. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov ID#NCT01015456.

Infection in Thai patients with systemic lupus erythematosus: a review of hospitalized patients.

Infection is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The authors conducted retrospective review of 488 admissions at King Chulalongkorn Memorial Hospital during a 5-year period (1994-1999) to determine the infectious complications in these patients. One hundred ninety-one patients with SL2 were admitted because of infection. Lower respiratory tract infection was the most commonly found in these patients (24.6%) followed by infections of the urinary tract (15.7%), skin (15.7%), septicemia (13.6%) and the musculoskeletal system (11.5%). The most common pathogens were Salmonella spp (12.6%), while Escherichiae coli (9.9%) and Mycobacterium tuberculosis (8.4), respectively.

Comprehensibility, reliability, validity, and responsiveness of the Thai version of the Health Assessment Questionnaire in Thai patients with rheumatoid arthritis.

INTRODUCTION: The Health Assessment Questionnaire Disability Index (HAQ-DI) is a commonly used instrument to assess functional status of patients with rheumatoid arthritis (RA). Translations and adaptations of the HAQ-DI have been carried out for use with RA patients in several countries. The objective of this study was to evaluate the psychometric properties of the Thai version of the HAQ-DI (Thai HAQ) in Thai patients with RA. METHODS: Comprehensibility of the Thai HAQ was assessed by 126 patients with RA from 6 medical centers in Thailand. Another group of 115 patients with active RA was enrolled to test the reliability (internal reliability and 1-week test-retest reliability), construct validity (correlations with other measures of RA disease activity), floor and ceiling effects, and sensitivity to change of the Thai HAQ at 3 months of treatment with disease-modifying antirheumatic drugs. RESULTS: More than 98% of the patients regarded the Thai HAQ as comprehensible. The internal consistency of the Thai HAQ was satisfactory with the overall Cronbach alpha of 0.91. The test-retest reliability of the Thai HAQ was acceptable with the intraclass correlation coefficient of 0.89. Moderate correlations between the Thai HAQ and other outcomes of RA disease activity were observed, except erythrocyte sedimentation rate, with the Spearman correlation coefficients ranging from 0.42 to 0.57. The responsiveness of the Thai HAQ was moderate, with a standardized response mean of 0.75 (95% confidence interval 0.56 to 0.94). CONCLUSIONS: The Thai HAQ is comprehensible, reliable, valid and sensitive to change in the evaluation of functional status of Thai patients with RA. The Thai HAQ is an essential tool to measure treatment effects and progression of disability in RA patients and should be applied in both clinical trials and routine clinical care settings.

Association of IL-18 gene polymorphism (-137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A).

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3' untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05-3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (-137) with arthritis (OR = 6.88, 95% CI = 1.54-42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83-56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (-137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56-291.66, P = 0.004).