Pathobiochemical Mechanisms Relating Iron Homeostasis with Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative for evaluation of the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.

YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis?

BACKGROUND: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. AIM: to investigate serum and synovial YKL-40 levels in relation to IL-1ß, TNF-α, and IL-6 in RA patients. MATERIALS AND METHODS: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1ß were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. RESULTS: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 ß (P<0.05). CONCLUSION: This is the first study finding a significant correlation between serum TNF-α and IL-1ß and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.

Pathobiochemical Mechanisms Relating Iron Homeostasis to Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative in evaluating the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.

Leflunomide in the treatment of refractory rheumatoid arthritis.

UNLABELLED: Leflunomide (LFL) is a modern immunomodulating medication belonging to the group of drugs that favourably affect the course of rheumatoid arthritis (RA). We present in this study the results of an open prospective trial on the effectiveness and side effects of LFL in clinically followed up patients with active RA refractory to other disease modifying anti-rheumatic drugs (DMARDS). At the onset of treatment with LFL the patients had at least 8 swollen and tender joints, the disease severity being assessed by both patients and physicians as over 3 cm VAS. ESR was higher than 40mm/lh. In all patients previous treatment with disease modifying drugs received for at least 3 months was insufficiently effective. It was discontinued prior to the therapy with LFL. Assessment of the therapeutic results was made at 3, 6 and 12 months after onset of LFL therapy. The following parameters were followed-up: 1) Number of tender joints, 2) Number of swollen joints, 3) Morning stiffness (min), 4) Global assessment of the patient (VAS 1-10 cm), 5) Global assessment of the physician (VAS 1-10 cm); 6) ESR - mm/lh; 7) Mean HAQ - the sum of all scores (0-3), divided by the number of the questions5; 8) SDAI index of RA activity6; 9) ACR20% and ACR50% positive therapeutic effect2. RESULTS: 82 patients (mean age 53.9 yrs, age range 20-70, 12 males, 70 females) were studied. RA was diagnosed in 80 (97.6%); RA combined with spondyloarthritis was diagnosed in 2 patients (2.4%). The mean duration of RA was 5.1 +/- 3.4 yrs. 70 patients (85.4%) were rheumatoid factor positive. The therapeutic effect from the administration of LFL was markedly good as early as at 3 months from beginning of treatment and was sustained significantly favourable at 12 months. The therapeutic effect of LFL referring to ACR20% is high - 36% at 3 months from onset of therapy and increased to 51% at 12 months. A grave side effect - leucopenia with granulocytopenia was observed in one female patient. LFL is a novel effective disease-modifying drug used to treat refractory RA. In a short term period - 3 to 6 months, LFL leads to a significant clinical and functional improvement of the patients.