Vitamin D Supplements May Benefit Lupus Patients

ScienceDaily (Oct. 17, 2012) — A new clinical study published in BioMedCentral’s open access journal Arthritis Research and Therapy provides preliminary evidence that vitamin D supplementation could be considered an immunomodulatory agent for systemic lupus erythematosus (SLE), a debilitating autoimmune disease characterized not only by skin, joint, neurological and renal symptoms, but also by inflammation of tissue linings in the body.

SLE is a T- and B-cell-dependent disease that causes an appearance of autoantibodies, causing the body to attack itself. Patients present with a depletion of regulatory T cells (Tregs) that normally protect against autoimmune disease, an increase in cytokine-producing T helper (Th) 17 cells and an increase in IFN-inducible genes, which trigger the body’s protective responses. Recent studies have shown that vitamin D could ameliorate these effects.

In a prospective clinical trial, Nathalie Costedoat-Chalumeau and colleagues set out to evaluate the safety and immunological effects of vitamin D supplementation in 20 SLE patients with low vitamin D levels. They observed these patients over six months and found that vitamin D was not only well-tolerated but, more importantly, there were no SLE flare-ups during the follow-up period.

Vitamin D supplementation in these patients caused an increase in beneficial CD4+ cells (mature Th cells), an increase in Treg cells and a decrease of effector Th1 and Th17 cells. It also induced a decrease of memory B cell and anti-DNA antibodies — all beneficial for SLE symptoms. The authors found that no modification of existing immunosuppressant drugs was needed, nor any new drugs initiated.

Although preliminary in nature, these findings suggest that vitamin D provides beneficial immunological effects for SLE, with a decrease in B memory cells and effector T cells, and an increase in Tregs. Costedoat-Chalumeau said “This should be confirmed in larger randomized controlled trials.”

Costedoat-Chalumeau believes that the findings confirm that vitamin D may also play other roles in the immune system. She said: “The study has highlighted interesting pathways to explore. Among the identified signatures, we observed the down-regulation of RNA polymerase functions and histone expression and the up-regulation of the TP53/CDKN1A-related pathway. These deserve further research owing to their possible involvement with a decrease in the accumulation of autoantigens and the activation and proliferation of autoreactive T and B lymphocytes.”

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Women With Lupus Have a Higher Risk for Preeclampsia

ScienceDaily (Oct. 30, 2012) — New research reports that women with systemic lupus erythematosus (SLE) have a two-fold increase in risk of preeclampsia — a dangerous condition in which pregnant women develop high blood pressure (hypertension) and protein in their urine (proteinuria) after 20 weeks of gestation. According to the findings published in Arthritis Care & Research, a journal of the American College of Rheumatology (ACR), use of Disease-Modifying Antirheumatic Drugs (DMARDs) during pregnancy was rare in the study population, but women who did use these medications show a statistically non-significant increase in preeclampsia risk. The risk could be explained by the severity of autoimmune disease among DMARD users.

Patients with autoimmune diseases such as SLE and rheumatoid arthritis (RA) are typically treated with DMARDs to prevent disease flares. DMARDs are a class of medications that treat the underlying autoimmune disease, not just symptoms of these diseases, and include: methotrexate (Rheumatrex, Trexall); anti-malarial drugs such as hydroxycholorquine (Plaquenil); and biologics such as etanercept (Enbrel) or adalimumab (Humira).

“Understanding how DMARD use impacts women with autoimmune disease is important, especially during pregnancy, as previous research found that women with SLE had at least a two-fold increase in preeclampsia risk and women with RA had a two-fold increase of this severe pregnancy complication,” said lead author Kristin Palmsten from Harvard School of Public Health.

To compare risk of preeclampsia in DMARD users, researchers used the British Columbia healthcare utilization database to identify 306,831 pregnancies in 224,827 women with and without autoimmune disease. Women who filled a prescription for DMARDs, non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids before pregnancy were considered “past users” and those who filled these prescriptions both before and during the first 20 weeks of pregnancy were designated “continuous users.”

Results show that pregnant women in this study had a median age of 30 years, with 0.3% of women diagnosed with RA or psoriasis; 0.2% with inflammatory bowel disease (IBS); 0.1% with SLE, and another 0.1% with multiple sclerosis (MS). Within this cohort, researchers found that 1,226 (0.4%) women used a DMARD in the year prior to pregnancy, while only 414 (0.1%) women used DMARDs while pregnant. The occurrence of preeclampsia in past DMARD, steroid, NSAIDs users was 2.3%, 2.7%, and 2.9%, respectively.

Further analysis indicates that a continuous DMARD user was at greater risk of preeclampsia (relative risk (RR) =2.29; not statistically significant) compared to past DMARD users. Preeclampsia risk was greater in women with SLE (RR=2.02) compared to women without an autoimmune disease. Restricting the analysis to women with autoimmune diseases weakened the preeclampsia relative risk in DMARD users.

Ms. Palmsten concludes, “Our findings uphold previous evidence, showing that women with SLE had twice the risk of developing preeclampsia. The statistically non-significant increase in preeclampsia risk found for DMARDs was reduced when we more fully accounted for the potential effect of the autoimmune diseases, suggesting that the underlying disease or severity of the disease was likely contributing to the increased risk of preeclampsia among DMARD users.” The authors advise that further studies are needed to confirm their findings, and research should focus on DMARD use and preeclampsia in women with specific autoimmune diseases.

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