Increased expression of the TNF superfamily member LIGHT/TNFSF14 and its receptors (HVEM and LTßR) in patients with systemic sclerosis.

OBJECTIVES: This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients. METHODS: Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects. RESULTS: Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud's phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT. CONCLUSION: These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.

Urinary angiotensinogen as a marker of intrarenal angiotensin II activity in adolescents with primary hypertension.

BACKGROUND: Experimental and epidemiological studies have demonstrated that urinary angiotensinogen (AGT) is a novel biomarker for the intrarenal activity of the renin-angiotensin system in hypertension (HT). Several large-scale epidemiological studies have shown that an elevated serum uric acid (SUA) level is associated with HT. The aim of our study was to assess urinary AGT excretion and its correlation with SUA level, the lipid profile, and the body mass index (BMI) Z-score in hypertensive adolescents. METHODS: Participants were divided into two groups: (1) the group with confirmed HT consisting of 55 subjects with primary HT and (2) the reference (R) group consisting of 33 subjects with white-coat HT. A commercial enzyme-linked immunosorbent assay (ELISA) kit was used to determine urinary AGT concentration. RESULTS: The urinary AGT/creatinine (cr.) ratio in subjects in the HT group was significantly higher than that in the reference group (p < 0.01) and showed a strong positive correlation with SUA (r = 0.47, p < 0.01). The relationship between the AGT/cr. ratio and SUA levels after controlling for age, gender and BMI Z-score continued to show a significant association. CONCLUSIONS: The most obvious finding to emerge from this study is that in adolescents with primary HT, the increased urinary excretion of AGT correlated with hyperuricemia, although large, multicenter studies are needed to confirm this observation.

Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate.

PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined.

[An up date on pulmonary hypertension related to systemic sclerosis]. / Nadcisnienie plucne w przebiegu twardziny ukladowej--aktualny stan wiedzy.

Systemic sclerosis (scleroderma) is a chronic, progressive connective tissue disease characterized by typical skin changes and internal organ involvement. Arterial pulmonary hypertension is found in approximately 10-15% of patients with systemic sclerosis, and is considered as one of the most fatal complications of the disease. When pulmonary hypertension secondary to scleroderma related interstitial lung disease, left-sided cardiac insufficiency and thrombo-embolic disease is also taken into account, the frequency of pulmonary hypertension in systemic sclerosis may be as high as.50%. Recent investigations brought new information considering the pathogenesis of pulmoanry hypertension and allowed new therapeutic approches to be introduced. Early diagnosis of pulmonary hypertension is a key issue in clinical practice, but it is a challange in patients with systemic disease such as systemic sclerosis. Current review presents up to date information on the pathogenesis, early diagnosis and treatment of pulmonary hypertension related to systemic sclerosis.

Urinary MMP-9/NGAL ratio as a potential marker of FSGS in nephrotic children.

BACKGROUND: The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. We hypothesized that matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) is a better marker of focal sclerosis in the glomerulus then matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) and matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 MMP2/TIMP-2. METHODS: The present study used a sample of 36 children and adolescents subdivided into two groups: I - 20 children with MCNS, subjected to examination twice: A - in relapse of nephrotic syndrome, before treatment and B - after regression of proteinuria; II - 16 children with FSGS. MMPs and TIMPs and NGAL levels were measured in the urine using ELISA kit. MMP-9/TIMP-1, MMP-2/TIMP-2 and MMP-9/NGAL ratios were calculated. RESULTS: Median NGAL/cr. was significantly higher in MCNS and FSGS patients when compared to healthy controls. Both, NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Contrary to FSGS children, in MCNS group, before treatment only NGAL/cr., but not MMP-9/cr. was increased. Urinary concentrations of NGAL and MMP-9 were highly associated with each other (NGAL/cr. vs. MMP-9/cr., r=0.485, p<0.01). Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We also found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) - 9.0; confidence interval (CI) 1.97-41.07]. CONCLUSION: MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children.

MR in neurological syndromes of connective tissue diseases.

BACKGROUND: Neurological complications in the course of SLE are mostly associated with vascular changes. An important role in their pathogenesis is played by immune mechanisms. The aim of the study was to determine the value of modern imaging techniques, with special reference to selected MR sequences (FLAIR, DWI) in the diagnosis of cerebral changes in patients with neurological symptoms of SLE. MATERIAL/METHODS: Fifty patients with neurological symptoms of SLE underwent CT and MR of CNS in routine sequences. In 12 cases EPI DWI sequences were also performed. Serum levels of antinuclear, anti-native DNA and antiphospholipid antibodies were also determined. RESULTS: The changes in CNS were detected in 48 patients in MR and in 42 patients in CT. Focal changes were observed in 29 cases, while atrophic changes were seen in the majority of subjects. In 10 cases, DWI showed changes typical for acute stroke. The extend and advancement of changes in CT and MR correlated with the severity of neurological symptoms; there was also a correlation between the changes and elevated levels of antiphospholipid antibodies. FLAIR was useful in the detection of gliosis and cortical scar, while DWI enabled us to detect acute ischaemic foci and to distinguish them from coexistent scars. CONCLUSIONS: MRI with FLAIR and DWI sequences enhances the sensitivity and specifity of neuroimaging techniques in the diagnosis of neuropsychiatric disease in SLE. There is a correlation between elevated titre of antiphospholipid antibodies and the presence of vascular changes in patients with neurological manifestations of SLE.

Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease.

OBJECTIVE: The leukotrienes are a family of arachidonic acid-derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B(4) (LTB(4)) and LTE(4) in the pathogenesis of scleroderma lung disease (SLD). METHODS: Nineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB(4) and LTE(4) were measured using enzyme immunoassay kits. RESULTS: Levels of LTB(4) and LTE(4) were significantly higher in SSc patients with SLD (251 +/- 170 pg/ml and 479 +/- 301 pg/ml, respectively), than those in patients without SLD (114 +/- 86 and 159 +/- 149 pg/ml) and those in normal controls (86 +/- 49 and 110 +/- 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB(4) (from 380 +/- 196 pg/ml to 155 +/- 123 pg/ml) but no significant difference in the levels of LTE(4) (from 697 +/- 325 pg/ml to 418 +/- 140 pg/ml). CONCLUSION: Our findings show that LTB(4) and LTE(4) levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.