Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

BACKGROUND: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. METHODS: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7-9, n-3 and n-6 FAs (patterns ω7-9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. RESULTS: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). CONCLUSIONS: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

Dietary recommendations of the French Society for Rheumatology for patients with chronic inflammatory rheumatic diseases.

This article presents the 1st set of dietary recommendations of the French Society for Rheumatology for patients suffering from chronic inflammatory rheumatic diseases (IRD) made by a working group consisting of 12 rheumatology experts, 3 physician nutrition specialists, 1 internal medicine specialist, 1 registered dietician and 3 representatives from patient associations. This group relied on a systematic literature review and on expert opinions, while taking into consideration not only the joint effects of diet in IRD but also the extra-articular ones. Eight general principles and nine recommendations were established. The general principles emphasize that nutritional advice is not a substitute for pharmacological treatment of IRD and that it is an integral part of the patients' overall care, which could help the patient actively participate in their care. The recommendations propose supporting weight loss in subjects who are overweight or obese, a Mediterranean-type diet and supplementation in polyunsaturated fatty acids, mainly omega-3. Conversely, gluten-free diets (in the absence of celiac disease), vegetarian/vegan diets, fasting and elimination of dairy products should not be proposed. Supplementation with vitamins or trace elements is not indicated for controlling chronic IRD activity, while the use of probiotics or spices is not recommended given the limited or disparate data.

Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. RESULTS: The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. CONCLUSIONS: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.

Collagen-induced arthritis and imiquimod-induced psoriasis develop independently of interleukin-33.

BACKGROUND: Interleukin (IL)-33 is a dual cytokine with both an alarmin role and a T helper 2 cell (Th2)-like inducing effect. It is involved in the pathogenesis of rheumatoid arthritis (RA) and its models; we recently demonstrated that exogenous IL-33 could inhibit collagen-induced arthritis (CIA) in C57BL/6 mice. However, its pathophysiological role in RA is unclear. Indeed, mice deficient in the IL-33 receptor ST2 show reduced susceptibility to arthritis, and the disease is not modified in IL-33-deficient mice. We examined the immune response in wild-type (WT) and IL-33-deficient mice with CIA. To further understand the role of endogenous IL-33 in inflammatory diseases, we studied its role in a skin psoriasis model. Mice on a C57BL/6 background were deficient in IL-33 but expressed lacZ under the IL-33 promoter. Therefore, IL-33 promotor activity could be analyzed by lacZ detection and IL-33 gene expression was analyzed by X-Gal staining in various mice compartments. Frequencies of CD4(+)FoxP3(+) regulatory T cells (Tregs) and Th1 and Th17 cells were evaluated by flow cytometry in WT and IL-33(-/-) mice. Bone resorption was studied by evaluating osteoclast activity on a synthetic mineral matrix. Psoriasis-like dermatitis was induced by application of imiquimod to the skin of mice. RESULTS: Severity of CIA was similar in IL-33(-/-) and WT littermates. Joints of IL-33(-/-) mice with CIA showed IL-33 promotor activity. In mice with CIA, frequencies of Tregs, Th1 and Th17 in the spleen or lymph nodes did not differ between the genotypes; osteoclast activity was higher but not significantly in IL-33(-/-) than WT mice. Psoriasis development did not differ between the genotypes. CONCLUSIONS: Despite its expression in the synovium of arthritic mice and normal keratinocytes, IL-33 is not required for CIA development in arthritis or psoriasis. Its absence does not induce a T cell shift toward Th1, Th17 or Treg subpopulations. Altogether, these data and our previous ones, showing that exogenous IL-33 can almost completely inhibit CIA development, suggest that this cytokine is not crucial for development of chronic inflammation. Studies of RA patients are needed to determine whether treatment targeting the IL-33/ST2 axis would be effective.

Bone fragility in sarcoidosis and relationships with calcium metabolism disorders: a cross sectional study on 142 patients.

INTRODUCTION: The prevention of fragility fractures in patients with sarcoidosis is a serious concern and the potential risk of hypercalcemia limits vitamin D and calcium supplementation. The objective of this study was to evaluate the risk factors for low bone mineral density (BMD) and fractures in sarcoidosis. In particular, we aimed to determine the link among bone fragility and calcium and vitamin D metabolism in this population. METHODS: We performed a cross-sectional analysis on 142 consecutive patients with histologically proven sarcoidosis. BMD and prevalence of vertebral fractures on X-rays were assessed and the association with potential risk factors was studied by regression analysis. RESULTS: Fragility fractures occurred in 23.5% of patients, despite a normal mean BMD in the study population. In a multivariate analysis, low dietary calcium, fracture, age, gender and menopause were associated with increased risk of low BMD. Low dietary calcium, high current corticosteroid dose and low creatinine clearance were associated with increased risk of fracture. Serum 25(OH)D between 10 and 20 ng/ml was significantly associated with higher BMD. Conversely, values greater than 20 ng/ml were associated with increased risk of fracture. Serum 25(OH)D level was inversely correlated with disease activity. Of note, vitamin D supplements increased serum 25(OH)D in a dose-dependent manner but had no effect on serum calcium level. CONCLUSIONS: Sarcoidosis patients have a high risk of fracture despite not having a lowered BMD suggesting that other independent factors are involved. Current corticosteroid dose, low dietary calcium and serum 25(OH)D levels are associated with bone fragility. In sarcoidosis, calcium and vitamin D supplementation might be warranted, but desirable 25(OH)D serum levels might be lower than those advised for the general population.

Modulation of anti-tumor necrosis factor alpha (TNF-α) antibody secretion in mice immunized with TNF-α kinoid.

Tumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-α and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-α neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-α antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-α antibody titers and their neutralizing capacity.

Vitamin D and inflammation.

Calcitriol, or 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) is a well-known endocrine regulator of calcium homeostasis. More recently, local calcitriol production by immune cells was shown to exert autocrine or paracrine immunomodulating effects. Immune cells that produce calcitriol also express the vitamin D receptor (VDR) and the enzymes needed to metabolize vitamin D3 (1α-, 25-, and 24-hydroxylases). Studies of animal models and cell cultures showed both direct and indirect immunomodulating effects involving the T cells, B cells, and antigen-presenting cells (dendritic cells and macrophages) and affecting both innate and adaptive immune responses. The overall effect is a switch from the Th1/Th17 response to the Th2/Treg profile. The immunomodulating effects of vitamin D may explain the reported epidemiological associations between vitamin D status and a large number of autoimmune and inflammatory diseases. Such associations have been suggested by observational studies not only in rheumatoid arthritis, lupus, inflammatory bowel disease, and type 1 diabetes; but also in infections, malignancies, transplant rejection, and cardiovascular disease. In animal models for these diseases, vitamin D supplementation has been found to produce therapeutic effects. Thus, vitamin D is a key focus for public health efforts and may hold promise for the treatment of dysimmune diseases.