Self-reactive IgE and anti-IgE therapy in autoimmune diseases.

Growing evidence indicates the pathogenic role of autoreactive IgE in autoimmune diseases. Incidence of autoimmune and allergic diseases in the industrialized countries is consistently icreasing, thus leading to concerted efforts to comprehend the regulation of IgE-mediated mechanisms. The first reports of a presence of IgE autoantibodies in patients with autoimmune diseases have been published a long time ago, and it is now recognized that self-reactive IgE can mediate inflammatory response in bullous pemhigoid, systemic lupus erythematosus, chronic urticaria, and atopic dermatitis. The advances in understanding the pathomechanisms of these disorders brought to a successful use of anti-IgE strategies in their management. The present review discusses the current state of knowledge on the IgE-mediated autoimmunity and anti-IgE treatment, and pave the way for further exploration of the subject.

Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study.

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63-0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value.

Autoimmune hemolytic anemia: current knowledge and perspectives.

Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

A case of bizarre posttransplant anti-glomerular basement membrane disease.

The non-collagenous (NC1) domain of α3 and α5 chains of type IV collagen are eminent targets of abnormal immune response in anti-glomerular basement membrane (anti-GBM) disease, which can be diagnosed by the presence of strong linear IgG staining along GBM detected by direct immunofluorescence. The presence of linear GBM fixation in renal allograft is a rare finding. We observed a 33-year-old male with de novo renal failure in a kidney transplant. An examination of a kidney biopsy specimen revealed, in light microscopy, mild mesangial hypercellularity together with mild focal interstitial fibrosis and sparse inflammatory infiltrate. In immunofluorescence microscopy strong linear IgG staining along the capillary walls was seen. Serum anti-GBM antibodies were negative and no mutation in exons coding NC1 domains of α3 and α5 chains of type IV collagen were detected. We described a rare case of a patient with atypical anti-GBM disease in renal allograft, caused probably by the same process which affected the native kidneys.

The importance of hypoalbuminemia in 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). 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.

The effect of caveolin-1 knockdown on interleukin-1ß-induced chemokine (C-C motif) ligand 2 expression in synovial fluid-derived fibroblast-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)-1ß 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-1ß-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.

Skin Barrier Function in Patients with Primary and Secondary Sjögren's Syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease. A large percentage of patients with SS suffer from dry skin, the cause and pathogenesis of which in this group of patients remains obscure. The aim of the present study was to investigate skin barrier function in patients with SS. Measurements of transepidermal water loss (TEWL) and hydration of stratum corneum (corneometry, CM) were performed in 30 female patients with SS (17 with primary SS and 13 with secondary SS), 20 patients with atopic dermatitis (AD) and 14 healthy controls. There were no statistically significant differences in TEWL values between the three investigated groups, while CM values were significantly decreased in patients with AD when compared with patients with SS and the healthy controls. Based on the obtained results, skin barrier function and hydration in patients with SS showed no functional alterations.

Levels of EGF and VEGF in patients with primary and secondary Sjögren's syndrome.

BACKGROUND: Aberrant angiogenesis plays a role in the pathogenesis of Sjögren's syndrome (SS). OBJECTIVES: The aim of this study was to compare the levels of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in stimulatory parotid saliva and in serum in healthy subjects (HS), patients with primary SS (pSS) and secondary SS (sSS) and to evaluate the expression of EGF, proangiogenic VEGF165 and antiangiogenic VEGF165 b mRNA isoforms. Additionally, we determined the salivary levels of serine/arginine splicing factor (SRSF1), which regulates VEGF165 and VEGF165 b expression. MATERIAL AND METHODS: The study comprised 34 women (16 with pSS and 18 with sSS) and healthy subjects for blood and saliva sampling. EGF and VEGF levels in saliva and serum and salivary SRSF1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The expression of VEGF165 , VEGF165 b and EGF in peripheral blood mononuclear cells (PBMC) was evaluated by quantitative polymerase chain reaction (qPCR). RESULTS: There were no differences in the levels of EGF, VEGF, SRSF1 and in the expression of the EGF, VEGF165 and VEGF165 b between HS and SS patients, or between pSS and sSS patients. The salivary levels of VEGF165 and EGF were significantly higher in pSS, sSS and HS than serum levels. Levels of SRSF1 correlated positively with VEGF and EGF levels. Levels of EGF, VEGF and SRSF1 correlated with each other. CONCLUSIONS: The balance of VEGF isoforms is not disturbed in SS. Saliva is more sensitive for the detection of EGF and VEGF than serum, but salivary levels of those proteins are not representative for SS.

Serum ICAM-1, VCAM-1 and E-selectin levels in patients with primary and secondary Sjögren's syndrome.

BACKGROUND: Typical features of Sjögren's syndrome (SS) are severe xerostomia and xerophthalmia which are basic diagnostic criteria. OBJECTIVES: The aim of this study was to compare the serum levels of soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sE-selectin between primary (pSS), secondary (sSS) and healthy subjects (HS). We correlated these results with selected clinical parameters of disease activity and parameters of the severity of xerostomia and xerophthalmia. MATERIAL AND METHODS: The serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by enzyme-linked immunosorbent assay (ELISA) in 16 patients with pSS, 18 with sSS and 15 HS. Eye dryness and xerostomia were assessed by the Schirmer's test, the Fox test and the visual analogue scale (VAS). RESULTS: The levels of sICAM-1 in pSS and sVCAM-1 in sSS patients were significantly higher when compared to HS (p = 0.02 and p = 0.048, respectively). There were no differences between pSS and sSS. In pSS, sVCAM-1 correlated positively with VAS (rS = 0.52, p = 0.04) and the Fox test (rS = 0.66, p=0.01). In sSS, sE-selectin correlated positively with sICAM-1 (rS = 0.54, p = 0.01), the duration of the disease (rS = 0.51, p = 0.03) and negatively with the Schirmer's test (rS = 0.59, p = 0.04). sICAM-1 correlated positively with the erythrocyte sedimentation rate (ESR) value (rS = 0.59, p = 0.01). CONCLUSIONS: sVCAM-1 reflects xerostomia in pSS. sICAM-1 and sE-selectin may be additional parameters of sSS activity.

Dialysis vintage and cardiovascular injury as factors influencing long-term survival in peritoneal dialysis and hemodialysis.

BACKGROUND: Cardiovascular (CV) incidents are the major cause of mortality in maintenance dialysis (MD) patients undergoing peritoneal dialysis (PD) or hemodialysis (HD). CV injury indicators may be useful to investigate the dialysis modality influence on survival. OBJECTIVES: The aim of this study was to compare selected laboratory and echocardiographic (ECHO) markers of CV injury in terms of dialysis vintage (DV), CV-related mortality and all-cause mortality. MATERIAL AND METHODS: The study involved 301 patients on HD (n = 301) and PD (n = 58), who were divided into subgroups according to DV. The subjects' medical histories included diabetes mellitus (DM), myocardial infarction (MI), stroke, CV deaths and deaths from non-CV causes. Their CV parameters were measured with ECHO for the left ventricle ejection fraction (EF), posterior wall (LVW) and interventricular septum (IVS). Serum analyses of cardiac troponin T (TnT) and N-terminal pro-brain natriuretic peptide (BNP) were also carried out. RESULTS: In the subgroup with a DV of 4 years, the PD and HD patients were of a similar age, and had similar mortality and morbidity rates and CV markers, except for thicker IVS in the HD patients. CONCLUSIONS: Focusing on the data analysis based on mortality, and both laboratory and echocardiographic markers of cardiovascular injury, PD seems to be a more favorable method of dialysis. The advantage of PD was noted in subjects with a DV < 2 years. HD showed no outcome benefit over PD in longer DV.

Serum alarm antiproteases in systemic sclerosis patients.

Alarm antiproteases, i.e. secretory leukocyte protease inhibitor ad elafin, are key mediators in innate immune response and integrate innate and adaptive immunity systems. The aim of the study was to assess clinical significance of serum levels of alarm antiproteases, elafin and secretory leukocyte protease inhibitor (SLPI) in patients with systemic sclerosis (SSc). Twenty-eight patients with SSc, 25 patients with rheumatoid arthritis (RA) and 22 healthy controls were recruited. Serum elafin and SLPI levels were examined using enzyme-linked immunosorbent assay (ELISA). The patients with SSc had significantly increased serum levels of SLPI in comparison with the RA patients and the healthy controls (p<0.01), and the RA patients presented significantly higher serum levels of elafin in comparison with the controls (p=0.003). In the SSc subgroup serum SLPI level negatively correlated with diffusing capacity of the lung for carbon monoxide (DLCO) (r=-0.41, p=0.03) and total lung capacity (r=-0.42, p=0.03). Both alarm antiproteases, elafin and SLPI could be potentially implicated in the pathogenesis of SSc and SLPI may be considered a candidate for serum biomarker of lung involvement in SSc.

The importance of residual renal function in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) patients with preserved residual diuresis have a lower risk of death and complications. Here we analyzed associations between residual diuresis and presence of fluid overload and biomarkers of cardiac strain and nutrition in PD patients. METHODS: Among 44 PD patients placed into three subgroups, depending on volume of residual diuresis (group A ≤ 500; group B 600-1900; and group C ≥ 2000 mL/day), we examined: overhydration (OH) assessed by bioimpedance analysis (BIA; yielding OH index OHBIA) and by clinical criteria (edema and hypertension); nutritional status (by subjective global assessment, SGA); metabolic status (electrolytes, serum lipid profile, CRP, and albumin); biomarkers of fluid overload and cardiac strain (N-terminal probrain natriuretic peptide, NT-proBNP, and troponin T, TnT); and, echocardiography and chest X-ray. RESULTS: With increasing residual diuresis in group A, B and C, fewer patients had signs of overhydration defined as OHBIA > 1.1 L (75.0, 42.9 and 33.3 %) or peripheral edema (25.0, 21.4 and 0 %) and NT-proBNP (15199 ± 16150 vs. 5930 ± 9256 vs. 2600 ± 3907 pg/mL; p < 0.05) and TnT (0.15 ± 0.17 vs. 0.07 ± 0.09 vs. 0.04 ± 0.03 ng/mL; p < 0.05) were significantly lower. Significant differences were found also in ejection fraction, SGA, and total cholesterol, albumin and hemoglobin levels whereas blood pressures and serum CRP did not differ significantly. CONCLUSION: Signs of OH and cardiac strain are common in PD patients, even in those with diuresis of 1000-2000 mL/day and with no clinical signs or symptoms, suggesting that even moderate decrease in residual renal function in PD patients associate with OH and other complications.

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.

Serum Clara cell 16-kDa protein levels and lung impairment in systemic sclerosis patients / Níveis séricos de proteína de células de Clara de 16 kDa e comprometimento pulmonar em pacientes com esclerose sistêmica

ABSTRACT 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.

RESUMO Objetivo: Avaliar a utilidade clínica das medições séricas da proteína de células de Clara de 16-kDa (CC16) em relação ao sistema de estadiamento para doença pulmonar intersticial associada a esclerose sistêmica (DPI-ES). Materiais e métodos: Foram determinados os níveis séricos de CC16 por ELISA em 28 pacientes com ES e 30 controles saudáveis e correlacionados com o sistema de estadiamento para DPI-ES em pacientes com ES. O envolvimento pulmonar foi avaliado funcionalmente (pletismografia corporal, capacidade de difusão de monóxido de carbono) e radiologicamente (extensão média da doença na tomografia computadorizada de alta resolução dos pulmões, TCAR) em pacientes com ES. Resultados: Foram encontradas diferenças estatisticamente significativas nos níveis séricos de CC16 entre pacientes com ES e controles saudáveis apenas em não tabagistas. No entanto, as concentrações séricas de CC16 eram significativamente elevadas em pacientes com extensão > 20% na TCAR em comparação com pacientes com extensão < 20% na TCAR (p = 0,01). Os níveis séricos de CC16 se correlacionaram positivamente com a extensão média da doença na TCAR (p = 0,04) e com a extensão de padrão reticular na TCAR (p < 0,01) e negativamente com a capacidade pulmonar total (CPT) (p = 0,03) e com os resultados do teste de caminhada de seis minutos (p < 0,01). Conclusões: Os níveis de CC16 podem ser considerados como biomarcadores séricos suplementares para a DPI-ES.

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.

Patterns of glomerular disease based on 4-year kidney biopsy material analyzed by light microscopy and immunofluorescence: a retrospective single-center analysis in Poland.

The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.

[Serum Clara cell 16-kDa protein (CC16) levels and lung impairment in systemic sclerosis patients]. / Níveis séricos de proteína de células de Clara de 16kDa (CC16) e comprometimento pulmonar em pacientes com esclerose sistêmica.

OBJECTIVE: To assess clinical utility of serum Clara cell 16-kDa protein (CC16) measurements in relation with staging system for systemic sclerosis associated interstitial lung disease (SSc-ILD). MATERIALS AND METHODS: Serum levels of CC16 were determined by ELISA in 28 SSc patients and 30 healthy controls, and correlated with staging system for SSc-ILD in SSc 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, HRCT) in SSc patients. RESULTS: We observed statistically significant differences in serum CC16 levels between SSc patients and healthy controls only in non-smokers. However, serum CC16 concentrations were significantly elevated in patients with HRCT extent>20% in comparison to patients with HRCT extent<20% (p=0.01). They correlated positively with average disease extent on HRCT (p=0.04), an extent of a reticular pattern on HRCT (p<0.01), and negatively with a total lung capacity (TLC) (p=0.03) and the results of the 6-min walk test (p<0.01). CONCLUSIONS: CC16 levels can be considered as a supplemental serum biomarker for SSc-ILD.

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.

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

AIM: 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. METHODS: Thirty-eight patients with SSc and 39 healthy controls were recruited. Serum IL-17, IL-21 and IL-23 levels were examined using enzyme-linked immunosorbent assay (ELISA). Lung involvement of SSc patients was assessed functionally (diffusing capacity of the lung for carbon monoxide [DLCO], body plethysmography) and radiologically (using average disease extent on high resolution computed tomography [HRCT] of the lungs according to the percentage of interstitial changes and quantified with a 30-point Warrick score) in 29 SSc patients. RESULTS: Serum IL-17 and IL-23 levels were significantly decreased and IL-21 levels were elevated in SSc patients when compared with controls (P < 0.001, P < 0.001, P < 0.01, respectively). The level of IL-17 was negatively associated with disease duration (P = 0.01) and positively with HRCT Warrick score (P = 0.03). IL-23 concentration negatively correlated with DLCO (P = 0.04), total lung capacity (TLC) (P = 0.01) and the 6-min walk test distance (P = 0.03). No associations were found between the cytokine levels and the average extent of the disease on HRCT. CONCLUSION: While the relationship between Th17-associated cytokines and ILD-SSc needs to be verified in a larger cohort of patients, the changes in concentrations of IL-17, IL-21 and IL-23 support the hypothesis that these cytokines may play a role in the pathogenesis of SSc.