SLE - systemic lupus erythematosus research

[Alohamora]

I know there are a couple of people with SLE here, so I thought I'd post a couple of research articles I've found while doing other reading.

Vitamin D deficiency in systemic lupus erythematosus.

Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS.

Medical University of South Carolina, Charleston, SC, USA. kamend@musc.edu

Evidence from animal models and prospective studies of RA, multiple sclerosis, and type-1 diabetes suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. We compared serum 25-hydroxyvitamin D (25(OH)D) levels between recently diagnosed SLE cases and matched controls, and examined disease characteristics in relationship to 25(OH)D among cases. Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls were used. We found a trend toward lower 25(OH)D levels in cases compared to controls, which was statistically significant in Caucasians (p=0.04), controlling for age, sex, season, and smoking. Overall, 67% of the subjects were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in 22 of the SLE cases, with presence of renal disease being the strongest predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). These results suggest vitamin D deficiency as a possible risk factor for SLE and provide guidance for future studies looking at a potential role of vitamin D in the prevention and/or treatment of SLE.

[Alohamora]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16541725&query_hl=7&itool=pubmed_docsum

[Progress and perspectives in the treatment of systemic lupus erythematosus]

[Article in Polish]

Robak E, Sysa-Jedrzejowska A, Wozniacka A.

Katedra i Klinika Dermatologii i Wenerologii, Uniwersytetu Medycznego w Lodzi. robaktad@csk.am.lodz.pl

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women in childbearing age. SLE tissue damage is mediated by autoantibodies, complement activation and immune complexes deposition. The disease is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially antinuclear antibodies. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and therapy guided by the activity and severity of the leading organ manifestation. Treatment ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids form the basis of all regimens. Antimalarials and azathioprine are important for treating mild and moderate SLE cases, especially for the long time. Cyclophosphamide given intravenously is the current gold standard for severe lupus nephritis. More recently new strategies for immunosuppression in SLE, that interfere with the syntesis of DNA and nucleotides have been developed (such as mycophenolate mofetil, fludarabine and cladribine). Other agents like cyclosporine and tacrolimus inhibit effect of the activation signals for T cells by inhibition of calcineurin. Some monoclonal antibodies against cytokines or components of the complement system interfere with the effector phase of the immune response. Abetimus (LJP-394) inhibits the production of anti-dsDNA antibodies and may prevent glomerulonephritis caused by anti-DNA containing immune complexes. Somatic gene therapy is also a novel approach in autoimmune disorders and my be a valuable method of SLE therapy in the future. The adrenal steroid prasterone (DHEA) has also shown benefitial effects in mild to moderate SLE. Finally, autologous stem cell transplantation can induce tolerance to self-antigens and cause significant improvement in SLE patients. However, new therapeutic strategies must be tested according to the established principles of clinical trial methods.

[Alohamora]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16373258&query_hl=7&itool=pubmed_docsum

Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus.

Nordmark G, Bengtsson C, Larsson A, Karlsson FA, Sturfelt G, Ronnblom L.

Department of Medical Sciences, Section of Rheumatology, University Hospital, Uppsala, Sweden. gunnel.nordmark@medsci.uu.se

The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( <or= 45/ >or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 "role emotional" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 "mental health" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.

[Alohamora]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12428233&query_hl=7&itool=pubmed_DocSum

Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial.

Chang DM, Lan JL, Lin HY, Luo SF.

Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. ming0503@ms3.hinet.net

OBJECTIVE: To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE). METHODS: In a multicenter randomized, double-blind, placebo-controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24. RESULTS: The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA -2.6 +/- 3.4 versus placebo -2.0 +/- 3.8, mean +/- SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA -5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA-treated patients compared with placebo-treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life-threatening reactions or serious safety issues were identified during this study. CONCLUSION: The overall results confirm that DHEA treatment was well-tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.