Biological therapies in rheumatic diseases.

The development of the biological drugs has revolutionized the therapeutic approach of the chronic inflammatory rheumatic diseases, particularly in patients resistant to standard treatment. These drugs are characterized by an innovative mechanism of action, based on the targeted inhibition of specific molecular or cellular targets directly involved in the pathogenesis of the diseases: pro-inflammatory cytokines (tumor necrosis factor, interleukin-1 and 6), CTLA-4, and molecules involved in the activation, differentiation and maturation of B cells. Their use has indeed allowed for a better prognosis in several rheumatic diseases (such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus) and to obtain a clinical remission. In the present review we give an overview of the biological drugs currently available for the treatment of the rheumatic diseases, analyzing the different mechanism of action, the therapeutic indications and efficacy data, and adverse events.

Peamaclein--a new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3.

BACKGROUND: Among the peach-derived allergens which are already known, the lipid transfer protein (Pru p 3) seems to be the one to exert severe allergic reactions. OBJECTIVE: To identify and characterize a new peach allergen causing a clinical picture similar to that of Pru p 3. METHODS: Patients were selected on the basis of their severe clinical reactivity and negative results to a panel of peach allergens available on the ISAC103 microarray. Several in-house and commercial preparations were compared. Several methods were used to characterize the newly identified molecule. Specific IgE and inhibition assays were performed using the Allergen micro-Beads Array (ABA) assay. RESULTS: Negative ISAC results to Pru p 3 were confirmed by additional testing in contrast with the positive results obtained by commercial Pru p 3-enriched peach peel extracts. The analyses of one of these preparations led to the identification of Peamaclein, a new allergenic protein. It is a small, basic, cysteine-rich, heat-stable, digestion-resistant protein, homologous to a potato antimicrobial peptide. Peamaclein was able to trigger positive skin test reactions and to bind IgE in the ABA assay. It displays an electrophoretic mobility and chromatographic behaviour similar to that of Pru p 3; therefore, it can be hidden in Pru p 3 preparations. In fact, Pru p 3-enriched peach peel extracts were found to contain both Pru p 3 and Peamaclein by means of comparative in vivo testing, and by biochemical and immunochemical assays. Commercially available anti-Pru p 3 polyclonal antibodies were found to have a double specificity for the two molecules. CONCLUSIONS AND CLINICAL RELEVANCE: A new allergen from peach belonging to a new family of allergenic proteins has been identified and characterized. This knowledge on Peamaclein will improve our understanding on the clinical aspects of the peach allergy and the quality of diagnostic reagents.

['ASIA' - Autoimmune/inflammatory syndrome induced by adjuvants: even and odd]. / 'SAIA' - Sindrome autoimmune/infiammatoria indotta da adiuvanti: presente e futuro.

Recently, Shoenfeld and Agmon-Levin described a potential new syndrome, namely ASIA - autoimmune/inflammatory syndrome induced by adjuvants, that comprises four medical conditions: siliconosis, the Gulf war syndrome, the macrophagic myofasciitis syndrome and post-vaccination phenomena, characterized by hyperactive immune responses accompanied by a similar complex of signs and symptoms. Most relevantly, these conditions share a linkage represented by adjuvants. This common soil may possibly induce autoimmune or auto-inflammatory diseases in humans as it was demonstrated in different animal models. Reconsidering under a unified umbrella this apparently detached condition is not only intriguing, but also provocative, and may help in unraveling novel pathogenetic mechanisms, preventive measures, and therapeutic targets.

Exploratory data analysis on the effects of non pharmacological treatment for knee osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a chronic rheumatic disease characterized by progressive cartilage destruction mediated by cytokines and other molecules. Chondrocyte activity and metabolism have attracted interest as targets of drug intervention, and spa-therapy can influence the serum levels of several cytokines. We investigated the effects of spa-therapy on clinical and ultrasonographic (US) findings and serum levels of cartilage oligomeric matrix protein (COMP) and several cytokines, chemokines, and growth factors in a prospective cohort of patients with symptomatic knee OA. METHODS: Patients (n=53) with primary symptomatic knee OA were treated for 12 consecutive days with locally applied mud-packs. Assessments were made at baseline, immediately after completion of the treatment cycle, and 6 and 12 months after completion of treatment. They included visual analogue scale (VAS) ratings of pain, the Lequesne algofunctional index for knee OA, and US with calculation of a semiquantitative score that expressed the severity of the local inflammatory process. Serum levels of 27 cytokines (including interferon--inducible protein-10 [IP-10]), chemokines, and growth factors were measured with multiplex bead-based immunoassays, and COMP levels were determined by ELISA. RESULTS: US scores, VAS pain ratings, and Lequesne indexes indicated significant improvement after spa-therapy and at the 6- and 12-month follow-ups. Serum IP-10 levels also dropped significantly (p=0.0035), and this reduction was positively correlated with improvement of the Lequesne index (p=0.031). CONCLUSIONS: In patients with knee OA, spa-therapy can modulate serum levels of proinflammatory cytokines/chemokines and produce improvements in joint pain and function that persists for up to 1 year.

Hydrogen peroxide as trigger of platelet aggregation.

In order to verify if H2O2 affects platelet function, platelet-rich plasma and human washed platelets were incubated with subthreshold concentrations (STC) of collagen or arachidonic acid or ADP and/or with 75-150 microM H2O2. While H2O2 alone did not affect platelet aggregation, it amplified platelet aggregation response in samples stimulated with STC of arachidonic acid and collagen but not in samples stimulated with STC of ADP. When platelets were preventively treated with aspirin, a cyclooxygenase inhibitor, the platelet activation by H2O2 was not observed. Thromboxane A2 (TxA2) was not produced by human washed platelets stimulated with STC of arachidonic acid, collagen or by H2O2 alone. On the contrary, when STC of agonists were tested on platelets supplemented with H2O2 an evident TxA2 production was seen. This effect was prevented by aspirin pretreatment or by the addition of catalase, an enzyme which destroys H2O2. This study suggests that H2O2 triggers the activation of platelets exposed to STC of collagen and arachidonic acid, via the cyclooxygenase pathway.