[Semeiology of "early arthritis"].

The main problems related to "early arthritis" are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the "early arthritis clinics" (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks – 6 months), morning stiffness of at least 1 hour, arthritis in ≥ 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration

A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release

Introduction The 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). Methods ARs 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. Results In 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. Conclusions Taken 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

Improved pregnancy outcome in patients with Rheumatoid Arthritis who followed an ideal clinical pathway

Among women with rheumatoid arthritis (RA) we aimed to assess the effect of optimal management of pregnancy, on a composite outcome of miscarriage and complicated birth

L'interessamento renale nella sindrome di Sjogren

Il coinvolgimnto renale è abbastanza frequente in corso di Sindrome di Sjogren. Nella maggioranza dei casi decorre in modo subclinico e asintomatioco. La lesione istopatologica più frequente è la nefrite tubulointerstiziale. Rara è la glomerulonefrite, segnalata per lo più in presenza di crioglobuline

HLA-G 14BP POLYMORPHISM REGULATES THE METHOTREXATE RESPONSE IN RHEUMATOID ARTHRITIS AND MAY BE PREDICTIVE OF RESPONSIVENESS

Background: Methotrexate (MTX) represents the most used anti-rheumatic drug in rheumatoid arthritis (RA). HLA-G antigens are inducible non classical MHC class Ib molecules important in maintaining anti-inflammatory conditions. HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp, that controls the specific mRNA stability and the protein levels. It has been reported that MTX therapy mediates an increase of Interleukin-10 (IL-10) producing cells. This cytokine up-regulates HLA-G expression. Objectives: To test the hypothesis of a MTX mediated HLA-G production and the possible relationship between the HLA-G 14 bp polymorphism and therapeutic responsiveness to MTX. Methods: Peripheral blood mononuclear cells (PBMCs) from 25 healthy subjects and 5 no-MTX-treated RA patients were activated with different MTX concentrations. sHLA-G and IL-10 production was investigated by specific immunoenzimatic assay (ELISA). HLA-G 14 bp polymorphism genotyping was also performed in 162 healthy subjects and in 156 RA patients, defined as "responders" (n=88) and "non responders" (n=68) to the MTX therapy after a 6 months therapeutic trial, on the basis of EULAR response criteria. Results: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14bp polymorphism in MTX treated RA patients confirmed an increase of the -14/-14 bp genotype in the responder group (p = 0.036; Fisher exact p test) (OR = 2.77 [95%CI 1.19 - 6.45] logistic regression model). Conclusion: Our results suggest that MTX induces the production of anti-inflammatory sHLA-G molecules that concur to the overall therapeutic response. Furthermore, the association between -14/-14 bp genotype and MTX responsiveness, indicates that HLA-G 14 bp polymorphism may be useful in the therapeutic decision during the early phases of the disease. A prospective study aimed to confirm these data is ongoing. References: Carosella ED, Moreau P, Aractingi S, Rouas-Freiss N. HLA-G: a shield against inflammatory aggression. Trends Immunol 2001; 10: 553-555. Hviid TV, Rizzo R, Christiansen OB, Melchiorri L, Lindhard A, Baricordi OR. HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms

Can HLA-G predict disease course in rheumatoid arthritis patients?

Rheumatoid arthritis (RA) remains a major clinical problem with many patients having persistent systemic inflammatory disease resulting in progressive erosive joint damage and high levels of disability. The goal of RA therapy has shifted to initiate treatment early and aggressively to achieve remission or low disease activity as quickly as possible. To achieve this 'treat-to-target' concept it is necessary to identify new biomarkers for disease progression and treatment follow-up and of new therapeutic targets. The focus of this review is to up-date the scientific knowledge on the expression of HLA-G molecules in RA and the possible implication in the future management of the disease

Role and function of A2A and A3 adenosine receptors in patients with ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A2A and A3AR subtypes is often associated with a reduction of the inflammatory status. The aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A2A and A3ARs in lymphocytes obtained from patients when compared with healthy subjects. A2A and A3AR agonists inhibited nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation and reduced inflammatory cytokines release, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Moreover, A2A and A3AR activation mediated a reduction of metalloproteinases (MMP)-1 and MMP-3. The effect of the agonists was abrogated by selective antagonists demonstrating the direct involvement of these receptor subtypes. Taken together, these data confirmed the involvement of ARs in chronic autoimmune rheumatic diseases highlighting the possibility to exploit A2A and A3ARs as therapeutic targets, with the aim to limit the inflammatory responses usually associated with RA, AS and PsA

Adenosine and adenosine receptors in rheumatoid arthritis

Rheumatoid arthritis is one of the most important chronic, progressive and disabling inflammatory diseases characterized by joint destructive process associated with synovial proliferation and secretion of high levels of proinflammatory mediators including cytokines and growth factors. Early diagnosis and effective therapy are crucial in order to prevent unfavorable outcome with joint deterioration and functional disability. Treatment of rheumatoid arthritis has progressed thanks to the advent of biologic drugs targeting different specific molecules and pathways involved in the inflammation. Considerable advances could be achieved in the identification of novel inflammatory biomarkers, good predictors of outcome. Adenosine, a well-known purine nucleoside interacting with A1, A2A, A2B and A3 adenosine receptors, is a potent endogenous inhibitor of inflammatory processes involved in the pathophysiology of a variety of CNS and peripheral diseases. As a consequence, selective agonists and/or antagonists of adenosine receptors could be useful in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, as they are already in other disorders in which inflammatory status is a clinical feature. © 2013 Future Medicine Ltd