Anna Olewicz-Gawlik

Interleukin-17 and interleukin-23: importance in the pathogenesis of lung impairment in patients with systemic sclerosis

T cell abnormalities with a focus on Th17 cells have been associated with the pathogenesis of systemic sclerosis (SSc) and interstitial lung disease (ILD). The aim of this study was to evaluate serum levels of interleukin (IL)‐17, IL‐21 and IL‐23 in SSc patients and to assess their relationship with ILD‐SSc.

Fucosylation of serum α1-acid glycoprotein in rheumatoid arthritis patients treated with infliximab

To analyze fucosylation of α1-acid glycoprotein (AGP) and to identify relations between AGP fucosylation and clinical and biochemical indices of disease activity in patients with rheumatoid arthritis (RA) treated with monoclonal antitumor necrosis factor (TNF) antibody infliximab, we examined 22 patients with RA who underwent a 54-week treatment with infliximab according to ATTRACT protocol. Blood samples were collected at baseline and before every infusion of infliximab. AGP fucosylation was measured using lectin-binding enzyme-linked immunosorbent assay utilizing fucose-specific lectin Aleuria aurantia (AAL). Moreover, the clinical status/activity, erythrocyte sedimentation rate, serum C-reactive protein (CRP), antitrypsin, α1-antichymotrypsin, AGP reactivity with concanavalin A, serum C3 and C4 complement components, and serum concentrations of TNF and soluble TNF type 1 and type 2 receptors were determined. In most patients, the fucosylation of AGP decreased rapidly after first infusion of infliximab and remained low during the 54-week therapy (p < 0.001). The decrease in AGP affinity to AAL closely followed changes in clinical and laboratory activity of RA and correlated with pretreatment concentrations of CRP (r = 0.4986, p < 0.05) and TNF (r = 0.5181, p < 0.05). The fucosylation of AGP can be a part of a negative feedback loop regulating migration of inflammatory cells and collagenase-3 activity in RA. The decrease in AGP fucosylation accompanied by improvement in clinical and biochemical parameters of RA could possibly reflect reduced migration of inflammatory cells to inflamed joints and AGP-mediated inhibition of collagenase-3 as a response to infliximab treatment.

Blood Serum Levels of Amino-Terminal Pro-C-Type Natriuretic Peptide in Patients with Systemic Sclerosis

The aim of this pilot study was to examine the association of serum levels of amino-terminal fragment of pro-C-type natriuretic peptide (NT-proCNP), as a substitute measure of serum C-type natriuretic peptide (CNP), with clinical and laboratory findings in patients with systemic sclerosis (SSc). Serum NT-proCNP, soluble (s)E-and sP-selectin levels were examined using specific enzyme-linked immunosorbent assay in 30 patients with SSc and 30 healthy controls. We found no statistically significant difference in serum levels of NT-proCNP neither between patients with SSc and healthy controls nor between those treated with immunosuppressive agents and untreated patients. Nevertheless, in the investigated SSc group, serum NT-proCNP levels correlated with the concentrations of C-reactive protein (CRP) and the duration of the disease. Both sP- and sE-selectin levels were elevated in SSc patients when compared to healthy subjects. Also they did not correlate with the concentrations of NT-proCNP. The results of the study indicate that serum NT-proCNP level is likely secondary to existing inflammation. However, the magnitude of CNP action in SSc and its possible role in the pathogenesis of the disease remains to be elucidated.

Oral mucosal manifestations in primary and secondary Sjögren syndrome and dry mouth syndrome

Introduction One of the most important symptoms of Sjögren syndrome is xerostomia. The oral cavity deprived of saliva and its natural lubricative, protective and antibacterial properties is prone to a number of unfavourable consequences. Aim To present the most important lesions on the oral mucosa in primary and secondary Sjögren syndrome and in dry mouth syndrome. Material and methods The study group comprised 55 patients including 52 women and 3 men aged 20–72 years (average: 28.25 years). Results Basing on the accepted criteria, primary Sjögren syndrome was diagnosed in 22 (40%) patients, secondary Sjögren syndrome in 18 (32.7%) patients, and dry mouth syndrome in 15 (27.27%) patients. The physical examination and the examination of the mouth were performed and history was elicited from every patient. Conclusions The most common pathologies appearing on the oral mucosa in primary and secondary Sjögren syndrome are angular cheilitis, cheilitis, increased lip dryness as well as non-specific ulcerations, aphthae and aphthoid conditions.

Large bone distractor for open reconstruction of articular fractures of the calcaneus

The results of operative treatment of two groups of patients with articular fractures of the calcaneus were evaluated. Twenty-three cases were treated surgically using a standard reconstruction procedure. In the second group of 19 patients a large bone distractor was used; it held the soft tissue flap retracted, while aiding in articular and tuberosity fragment reduction and increasing visualisation by distraction of the posterior talocalcaneal joint. After a year, the anatomical and functional results, together with the operative time, were evaluated. All fractures healed with good or very good anatomical results. All cases, except those with complications (n = 3), achieved good (n = 28) or very good (n = 11) functional scoring. The distractor group had significantly shorter operative times, and less manpower was needed during surgery. We conclude that the large bone distractor is a useful tool in open reconstruction of articular calcaneal fractures.

Transforming growth factor-β1 in plaque morphea

Introduction Morphea (localized scleroderma) is a rare cutaneous disease characterized by skin fibrosis of unknown pathogenesis. Transforming growth factor-β (TGF-β) is a potent profibrotic factor. The role of TGF-β in morphea remains unclear. Aim The goal of this study was to estimate the expression level of TGF-β1 in skin and peripheral blood mononuclear cells as well as the plasma levels of TGF-β1 in plaque morphea (MEP). Material and methods The study involved 20 MEP patients. Three control groups were involved: 1 – plasma: 36 healthy volunteers; 2 – PBMC: 47 healthy volunteers; 3 – skin biopsies: 13 samples collected during mastectomy (breast cancer was not skin involved). The analysis of TGF-β1 plasma levels was performed with the use an adequate ELISA kit, while real-time polymerase chain reaction was employed for the expression of TGF-β1 in peripheral blood mononuclear cells (PBMC) and skin. Results In our study we have not detected differences in TGF-β 1 expression in PBMC, skin, nor in plasma levels of TGF-β1 between MEP patients and healthy controls, regardless of disease activity and its duration. Conclusions The results of our study contradict the claim of the substantial role of TGF-β1 in the most common morphea subtype – MEP.

Serum Clara cell 16-kDa protein levels and lung impairment in systemic sclerosis patients

OBJECTIVE To assess clinical utility of serum Clara cell 16-kDa protein measurements in relation with staging system for systemic sclerosis associated interstitial lung disease. MATERIALS AND METHODS Serum levels of Clara cell 16-kDa protein were determined by ELISA in 28 systemic sclerosis patients and 30 healthy controls, and correlated with staging system for systemic sclerosis associated interstitial lung disease in systemic sclerosis patients. Lung involvement was assessed functionally (body plethysmography, diffusing capacity of the lung for carbon monoxide) and radiologically (an average disease extent on high resolution computed tomography of the lungs) in SSc patients. RESULTS We observed statistically significant differences in serum Clara cell 16-kDa protein levels between systemic sclerosis patients and healthy controls only in non-smokers. However, serum Clara cell 16-kDa protein concentrations were significantly elevated in patients with high resolution computed tomography extent >20% in comparison to patients with high resolution computed tomography extent <20% (p=0.01). They correlated positively with average disease extent on high resolution computed tomography (p=0.04), an extent of a reticular pattern on high resolution computed tomography (p<0.01), and negatively with a total lung capacity (p=0.03) and the results of the 6-min walk test (p<0.01). CONCLUSIONS Clara cell 16-kDa protein levels can be considered as a supplemental serum biomarker for systemic sclerosis associated interstitial lung disease.

Quantitative analysis of elastase and cathepsin G mRNA levels in peripheral blood CD14(+) cells from patients with rheumatoid arthritis.

In rheumatoid arthritis (RA) activity of serine proteases is an important factor contributing to destructive changes in the joints. The aim of this study was to compare elastase (ELANE) and cathepsin G (CTSG) mRNA levels in peripheral blood CD14(+) cells obtained from RA patients, healthy subjects (HS) and patients with osteoarthritis (OA). CD14(+) cells were isolated from peripheral blood by positive magnetic selection. The expression levels of ELANE and CTSG were determined by quantitative real-time PCR. ELANE mRNA expression was significantly higher in RA patients when compared to HS (p<0.001) and OA patients (p<0.001). The results suggest that in RA, peripheral blood CD14(+) cells express serine protease mRNA as a result of systemic mechanisms probably related to inflammation/cytokines before entering inflamed joints.

Theeffect of caveolin-1 knockdown on interleukin-1β-inducedchemokine (C-C motif) ligand 2 expression in synovial fluid-derivedfibroblast-like synoviocytes from patients with rheumatoid arthritis

BACKGROUND Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destructive changes in peripheral joints and their irreversible deformity. The influx of chemoattractant-mediated inflammatory cells to the joints is one of the main features of RA. OBJECTIVES The aim of this study was to investigate the effect of a knockdown of caveolin-1 (CAV1), a known regulator of multiple cell signaling pathways, on chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) expression in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs) obtained from patients with RA. MATERIAL AND METHODS Primary cell cultures of sfd-FLSs were established from RA synovial fluids. Cells were transiently transfected with small interfering RNA (siRNA) specific for CAV1, and then incubated with interleukin (IL)-1β to induce CCL2 expression. The expression levels of CAV1 and CCL2 were assessed at transcript level, using quantitative polymerase chain reaction (qPCR) and at protein level by enzyme-linked immunosorbent assay (ELISA) and western blotting analysis. RESULTS A transient CAV1 knockdown in sfd-FLSs resulted in a decrease in the IL-1β-induced CCL2 mRNA expression level vs non-transfected cells and cells transfected with non-targeting siRNA. The concentration of secreted CCL2 was not affected significantly. CONCLUSIONS Our study demonstrates that CCL2 expression in sfd-FLSs is CAV1-dependent, but only at transcript level. As the function of CAV1 has not been unequivocally determined, more studies are needed to confirm the role of CAV1 in inflammatory processes related to RA.

The importance of hypoalbuminemiain peritoneal dialysis patients: Impact of gender

BACKGROUND High mortality in peritoneal dialysis (PD) patients is associated with the presence of nontraditional cardiovascular risk factors, such as malnutrition. However, hypoalbuminemia in patients undergoing PD may have gender-dependent consequences. OBJECTIVES The aim of the study was to evaluate the relationship between hypoalbuminemia, overhydration (OH), inflammation, and cardiovascular risk, depending on gender. MATERIAL AND METHODS The group studied consisted of 54 PD patients: 26 male (mean age: 59 ±19 years) and 28 female (mean age: 52 ±15 years) patients. Serum albumin levels were measured routinely by the hospital central laboratory. The degree of OH was assessed by bioelectrical impedance analysis (BIA). Serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6 were measured as inflammatory markers. Levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and troponin T (TnT) were used to assess cardiovascular risk. RESULTS Median serum albumin concentration was 3.9 g/dL (3.6-4.2 g/dL). Both genders were comparable regarding most parameters except body weight (79 ±16 kg vs 67 ±16 kg; p = 0.009), but no differences were observed in body mass index (BMI) (26.3 ±5.0 kg/m2 vs 26.2 ±5.9 kg/m2; non significant (NS)). There was also no difference in the prevalence of hypoalbuminemia between female and male PD patients (23% vs 21%; NS). In females, low serum albumin concentrations were associated with OH, inflammation and cardiovascular risk, while in males serum albumin levels correlated with the parameters of dialysis and cardiovascular risk. CONCLUSIONS The impact of hypoalbuminemia may be gender-dependent. It seems that hypoalbuminemia is more important for female patients. It is also possible that different mechanisms regulate serum albumin concentration in female and male PD patients.