Eugeniusz J. Kucharz

A Decreased Serum Leptin Level in Patients with Systemic Sclerosis

Abstract Serum leptin levels were determined in 31 women with systemic sclerosis and 24 age-matched healthy controls. Both groups were divided into premenopausal and postmenopausal subgroups. A decreased serum leptin was found in the patients with systemic sclerosis. The premenopausal patients and controls had higher serum leptin than those in the postmenopausal subgroups. Serum leptin correlated with body mass index in the patients with systemic sclerosis.

Etanercept increases adiponectin level in woman with rheumatoid arthritis

Dear Editor, We read with interest the paper by Serelis J. et al. “Effect of anti-TNF treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis” [1]. This study gives a new insight into the influence of TNF alpha and its inhibition on fat tissue metabolism in patients with chronic inflammatory polyarthropaty—rheumatoid arthritis (RA). The paper is of special importance in the light of the current studies that highlight the burden of premature atherosclerosis and its fatal complication among RA patients. The results from the study do not only go far beyond assessment of fat tissue metabolism but may also give the new information on pathogenesis of atherosclerosis in RA patients and the role of anti-TNF alpha treatment among the patients with this disease. To support the observation of the authors, we would like to present a similar study in RA patients treated with another TNF inhibitor—etanercept. In the group of 18 women with RA aged 45.5 (range, 21–55), we determine the plasma adiponectin levels before and after 3 months of treatment with etanercept and compare it with healthy age-matched women. The disease activity (DAS28) and serum adiponectin concentration were measured before treatment and after 3 months. The body composition was measured by DEXA only before treatment in patients and compared to controls. The levels of adiponectin were significantly higher in patients before treatment than in the controls—12.3 μg/ml (range, 5.7–21.1) vs 9.2 μg/ml (range, 3.5–15.3). Our results show also marked elevation of adiponectin levels in the patients after the 3-month treatment of etanercept as compared to the period before the treatment, which is in the agreement with the results of authors. Moreover, we found that increment of adiponectin level was not related to changes of disease activity (p>0.05) that support rather the directed influence of pro-inflammatory cytokine cascades on adiponectin concentration than general inflammation state. Taking into account the fact that various antiTNF alpha agents have a different influence on total TNF alpha levels in the patients treated (in some studies, etanercept does not reduce TNF alpha level [2]), we may also postulate that contradictory results reported in the literature reflect various changes in TNF alpha levels in the course of treatment with various anti-TNF alpha agents. We may also suggest that TNF alpha seems to be a key cytokine that regulates adiponectin level in patients with RA. On the other hand, adiponectin exhibits strong anti-inflammatory activity. Adiponectin paradoxically stimulates TNF alpha release from macrophages; however, this is a transient effect followed by TNF-alpha-induced IL-10 elevation [3]. In RA, elevated adiponectin level may reflect anti-inflammatory properties of this adipocytokine and may satisfactorily explain its elevation in comparison to the healthy subjects [4]. The contradictory results in studies using various anti-TNF alpha agents show rather different levels of TNF alpha suppression, with adiponectin level being higher when TNF alpha reduction is not prominent.

Relationship between adiponectin, leptin, IGF-1 and total lipid peroxides plasma concentrations in patients with systemic sclerosis: possible role in disease development

The relationship between adiponectin, leptin, insulin‐like growth factor‐1 (IGF‐1) and total lipid peroxide (TLP) concentrations, and its possible role in the development of diffuse cutaneous systemic sclerosis (dcSSc), were evaluated in this study.

Alterations of plasma glycosaminoglycan profile in patients with rheumatoid arthritis in relation to disease activity

BACKGROUND Qualitative and quantitative evaluation of plasma glycosaminoglycans (GAGs) of rheumatoid arthritis (RA) patients in relation to disease activity estimated by DAS28 score was evaluated. METHODS GAGs were quantified by hexuronic acid assay and electrophoretic fractionation. Keratan sulfate (KS) and hyaluronic acid (HA) were measured by immunoassay. RESULTS Chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) in plasma of healthy subjects and RA patients were stated. Total GAGs, CS, HS/H and HA levels were higher in patients with high and moderate disease activity than in controls. Total GAGs and CS levels in patients with high disease activity were elevated in comparison to patients with low disease activity. HS/H levels in patients with high and moderate activity were elevated in comparison to those with low disease activity. KS levels were increased in all patient groups in comparison to controls. Total GAGs, CS, HS/H and HA levels were positively correlated with DAS28 and CRP. CONCLUSIONS Structural tissue damage/remodeling of the extracellular matrix occurs in RA, which is reflected in the qualitative and quantitative changes of plasma GAGs. The above changes depend on DAS28 and may contribute to systemic changes in the properties of the extracellular matrix.

Increased Adiponectin Levels in Women with Rheumatoid Arthritis After Etanercept Treatment

To the Editor: We read with great interest the report by Dr. Nagashima, et al , “Increase in plasma levels of adiponectin after administration of anti-tumor necrosis factor (TNF) agents in patients with rheumatoid arthritis”1. The article is of special importance in regard to accelerated atherosclerosis among patients with connective tissue disease, including rheumatoid arthritis (RA). In the study, the elevation of total and high molecular weight adiponectin was observed in patients with RA treated with both etanercept and infliximab. To support the observations of those authors, we share our … Address reprint requests to Dr. Kotyla. E-mail: pkotyla{at}slam.katowice.pl

Calprotectin in rheumatic diseases: a review

Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren’s syndrome) is presented.

Subacute cutaneous lupus erythematosus in the course of rheumatoid arthritis: a relationship with TNF-α antagonists and rituximab therapy?

Abstract Introduction: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is caused by different medicines, first of all: calcium channel blockers, angiotensin converting enzyme inhibitors, thiazides, terbinafine, statins and antagonists of tumor necrosis factor-α (TNF-α). DI-SCLE does not distinguish from idiopathic form of the disease, clinically, histopathologically and immunologically. However, receding of symptoms is observed after recapture of the provoking drug. Aim: To present a patient with rheumatoid arthritis (RA), who developed SCLE after treatment with TNF-α antagonists and rituximab. Case report: In a 31-year-old woman with RA leucopenia due to treatment with etanercept and adalimumab was observed. Therefore, the treatment was changed to rituximab, but after starting the therapy, erythematous and oedematous skin lesions of an oval or annular shape appeared on the cheeks, auricles, lips and the decolette. Histopathological evaluation of the skin lesions revealed SCLE. Ro/SS-A and La/SS-B antibodies were detected in serum. Regression of skin lesions and hematologic disturbances was achieved after starting corticosteroid therapy. Conclusions: Co-existence of SCLE with RA should be considered in some patients. The role of TNF-α antagonists and rituximab therapy in induction of idiopathic form of SCLE requires further investigations.

Correlation between erythrocyte sedimentation rate and C-reactive protein level in patients with rheumatic diseases

Objectives Erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) are the acute phase reactants most commonly determined in patients with rheumatic diseases. The indices are affected by different factors, but both of them are applied for evaluation of the disease activity in patients with inflammatory disorders of the musculoskeletal system. Material and methods The authors compared the results of ESR and CRP, which were carried out during routine diagnosis in 200 patients admitted to the Department of Rheumatology. Results A significant correlation between ESR and CRP was found (ESR after 1 h/CRP: correlation coefficient 0.6944, ESR after 2 h/CRP: correlation coefficient 0.6126). There was no difference in ESR or CRP between male and female patients, and patients older than 40 years had higher ESR and CRP. Conclusions The obtained results support the usefulness of both indices in the clinical practice of rheumatologists.

FRI0186 Circadian profile of serum melatonin in patients with systemic sclerosis

Background Melatonin (MT) is secreted by the pineal gland and a circadian rhythm of MT secretion is related to light-darkness exposure. MT has been found to influence immune and endocrine functions and is a free radical scavanger. Immune abnormalities and disturbed endocrine secretion have been reported in patients with systemic sclerosis (SSc). Additionally, some of the patients have sleep disturbances or depression, a factors known to effect the MT level. All these findings suggest possible role of MT in pathogenesis of some phenomena seen in SSc patients. Objectives The aim of the study was to evaluate the circadian profile of serum MT levels in patients with SSc. Methods Six women with definite SSc, aged 32.4+1.8 yrs (symptoms duration 4–7 yrs) and six age-matched healthy women were investigated. Blood samples were drawn at 8.00, 12.00, 16.00, 20.00, 22.00, 24.00, 02.00, 04.00. 06.00. Light exposure of the subjects was from 07.30 to 21.00. MT was determined with ELISA method. Results A significant circadian rhythm of serum MT was detected in all investigated subjects. Serum MT levels were lower in the SSc patients than in the controls, MESOR = 21.4 pg/ml and 47.3 pg/ml, in the patients and controls, respectively. In the SSc patients, the night increase in MT was also relatively lower when compared to the daily levels. Maximal values were found between 02.00–04.00 both in the patients and controls. Conclusion The general nature of the circadian serum MT rhythm is maintained in the SSc patients although secretion of MT is depressed. The mechanism of impaired MT secretion remains unknown. It may be speculated that a low MT level is involved in development of immune abnormalities, neuroendocrine disfunctions and/or impaired free radical elimination. All these phenomena may contribute to development of fibrosis.

Tofacitinib in the treatment of patients with rheumatoid arthritis: position statement of experts of the Polish Society for Rheumatology

Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The presented article discusses the mechanism of action and the clinical application of tofacitinib. Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with biological drugs already available.