Ανοσοβιολογικοί παράγοντες στη θεραπεία των αυτοάνοσων ρευματικών νοσημάτων

Abstract

Patients with Rheumatoid Arthritis (RA) are prone to aggressive atherosclerosis, resulting to increased morbidity and mortality in comparison with the general population, mainly due to cardiovascular disease. Increased cardiovascular risk in RA is the result of interaction between traditional and disease-associated risk factors. In addition, active RA is associated with changes of body composition (increase of the fat mass, reduction of muscular and bone mass), which may relate to the increase of cardiovascular risk. In both obesity and atherosclerotic disease, two conditions with a small load of inflammation, serum concentration of adiponectin is low, while concentration of TNF-α are relatively high. In RA there is high grade systemic inflammation and high concentrations of TNF-α are detected on serum and synovium, while serum adiponectin levels do not obey to suppression by TNF-α. Since it is well known now, that RA responds to anti-TNF-α treatment, we have tried to investigate the changes to adiponectin serum levels and body composition in patients with RA. Ηn addition we investigated the influence of anti-TNF-α treatment on cardiovascular disease incidence. This thesis consists in 2 studies, one of which is prospective and the other is retrospective. In the first study we investigated with DEXA-absorptiometry changes in body composition, serum adiponectin concentrations and disease activity on 19 women with RA, after one year of anti-TNF-α treatment. In the second study we investigated the cardiovascular disease incidence on 325 patients with RA, who had follow-up at least 2 years and median follow-up of 10 years, and correlated the events with traditional and disease associated risk factors, including TNF-α treatment. The results have shown: 1. After one year of anti-TNF-α treatment, a rise on serum adiponectin concentration was detected, eventhough there was no change of body composition. 2. Cardiovascular disease incidence was not greater than that of the average Greek population 3. Anti-TNF-α treatment conferred no extra protection from cardiovascular disease in comparison with other treatments, provided they were effective. 4. Risk factors for CVD incidence were late disease onset and high disease activity after one year of treatment. 5. Among all risk factors hypertension had the dominant influence on CVD development In conclusion anti-TNF-alpha treatment increases serum adiponectin levels and in the subset of the responders, is associated with reduction of CVD incidence.

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