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Objective. Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti-tumor necrosis factor ␣ (anti-TNF␣) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs.

IntroductionThe reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A2A and A3 adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A2A and A3ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS).MethodsARs were analyzed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from early and established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release was carried out by A2A and A3AR activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also studied.ResultsIn lymphocytes obtained from RA patients, A2A and A3ARs were up-regulated if compared with healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-α, IL-1β and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR density inversely correlated with DAS28 and DAS suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation.ConclusionsTaken together these data demonstrate that the inflammatory and clinical responses in RA are regulated by A2A and A3ARs and support the use of A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease mainly mediated by the deposit of immune complexes and defects in T lymphocytes and antigen-presenting cells along with a high production of T-helper 2 cytokines. A tolerance-inducible function of nonclassical class Ib human leukocyte antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian) and analyzed the plasma levels of sHLA-G and interleukin-10 (IL-10) in a subset of SLE patients and healthy subjects (Italian and Danish). A significant increase of the +14 bp HLA-G allele was detected in the Italian SLE patients compared with HS [P = 0.003, OR 1.44 (95% CI 1.13-1.82)]. A significant increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results confirmed higher concentrations of IL-10-positive plasma in SLE patients. These results support a potential role for HLA-G in the susceptibility of SLE.

A new algorithm based on a probability score was developed and validated to determine the relationship between NP events and SLE.