AB0325 SERUM HEPCIDIN LEVEL IN REFRACTORY RHEUMATOID ARTHRITIS: ITS RELATIONSHIP TO DISEASE ACTIVITY AND CHRONIC HYPOXIA

Abstract

BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) was recently defined by a EULAR study group and, as a disease category it is largely complicated and under-researched. Patient multimorbidities, in particular chronic hypoxia, may play a significant role in the response to therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) and in the disease classification as D2T RA. Iron metabolism disorders are the leading pathogenic factors in progression of anemia of chronic disease and chronic hypoxia. Hepcidin is a key negative acute-phase regulator of duodenal iron absorption, mobilization and considered as a mediator of anemia in inflammation. However, present studies on serum hepcidin levels in patients with RA and multimorbidity are inconsistentObjectivesTo investigate the relationship between hepcidin levels, markers of inflammatory activity and hemoglobin (Hb) levels in patients with RA and multimorbidity.MethodsThe investigation enrolled 71 patients (mean age, 54.8±14.8 years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0±1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity.Аnemia of inflammation (AI) was diagnosed in 42 patients. Anemia was defined as hemoglobin <12g/dL and <13.5g/dL, in men and women, respectively. AI was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum hepcidin, as well as IL-6 levels were also measured. Patients with iron-deficiency anemia were excluded.ResultsChronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29%, hypercholesterolemia in 20%, obesity in 13.5%), chronic hypoxia (new-onset anemia verified in 24% of cases).RA patients with AI and with normal Hb levels (n=29) were comparable (p>0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9).In RA patients with AI we found a strong positive correlation between serum hepcidin and ferritin levels (r=0.623, p=0.009). There was a positive correlation between serum hepcidin and IL-6 levels (r=0.546, p=0.023). We found a strong negative correlation between serum hepcidin concentrations and Hb levels (r=0.528, p=0.029), but reliable correlation between DAS28, CRP and ESR was not revealed.In RA patients without anemia, the level of hepcidin positively correlated with the inflammatory activity parameters including CRP, ESR and DAS28, no correlation between the Hb and ferritin levels was revealed.ConclusionOur data support the hypothesis that IL-6-driven hepcidin production mediates AI in RA patients and might play a role in the pathogenesis of anemia associated with RA. In RA patients with chronic hypoxia, serum hepcidin level was significantly higher and perform better than traditional yardsticks in identifying anemia inflammation.