Activation of the JAK/STAT pathway in Behcet's disease.

Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite.

BACKGROUND: We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). METHODS: Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4(+) CD25(+) FOXP3(+) T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-ß responses were assessed. RESULTS: In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month - baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF-ß were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). CONCLUSION: Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.

Flow cytometric detection of anti-AB antibody titers in blood group O recipients of blood group A2 donor kidneys.

AIM: ABO-incompatible kidney transplantation has been accepted for end-stage renal failure patients who have no ready opportunity for a deceased or living donor. Antibody titration for ABO-incompatible renal transplantation is not only difficult but also lacks conformity among laboratories. Herein we analyzed 20 living related renal transplant couples to detect recipient anti-A2 antibody using flow cytometric analysis. MATERIALS AND METHODS: Patients were admitted to our center for renal transplantation between January 1999 and December 2010. All but four of them had undergone a previous renal transplantation from an ABO-compatible donor but experienced graft failure. All donor blood groups were subtyped by our blood bank using a lectin-based dilution assay. To detect recipient anti-A2 antibody titers we used a tube hemagglutination method. A/B antibody titer analysis by flow cytometry incubated serially diluted serum samples with donor erythrocytes. Each analysis was repeated three times over a 2-week period using an older and the last sera simultaneously. RESULTS: The 13 male and 7 female patients showed our overall mean age of 32 ± 12 years. All patients had panel-reactive antibody levels below 15%. The level of flow cytometric antibody titers did not vary upon repeated analysis (P = .01). When compared with the tube method there was a discrepancy of the level at which the antibody titer became negative. DISCUSSION: Flow cytometric antibody titration is a practical and rapid technique to determine the amount of anti-A2 antibody in renal recipients.

Effects of malnutrition on oxidative burst functions and infection episodes in children with acute lymphoblastic leukemia.

INTRODUCTION: The aim of this study was to determine the effect of malnutrition on oxidative burst functions (OBF) of neutrophils in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight patients with ALL and thirty healthy controls were enrolled to the study. Thirteen patients with ALL were found to have malnutrition. While neutrophil OBF of ALL patients without malnutrition were studied both before induction chemotherapy and 3 months after, the same functions in ALL patients with malnutrition were studied both before induction chemotherapy and when the nutritional status improved. Control group were studied at admission and 3 months later. RESULTS: The OBF of ALL patients with and without malnutrition before induction chemotherapy were found to be significantly lower than the control group (P = 0.009), whereas the OBF were found to be similar in both patient groups with ALL (P = 0.27). The median infection episode rate and the duration of antibiotics therapy during the study period were similar in both patient groups with ALL. The repeated OBF of both patient groups with ALL were shown to increase to similar values with the control group in the third month of chemotherapy (P = 0.002). The median infection episode rate during the first month of chemotherapy was shown to decrease significantly during the third month of chemotherapy in both patient with ALL groups (P < 0.001). CONCLUSIONS: We have not been able to demonstrate an overt effect of malnutrition on OBF. However, our results still need to be verified via further larger scaled studies of OBF in leukemic children with and without malnutrition.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis.

BACKGROUND: Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production. OBJECTIVES: To investigate the possible role of leptin in psoriasis pathogenesis. METHODS: Forty-three patients with psoriasis, 10 diseased and 10 healthy controls with normal body mass index were included. Serum fasting leptin levels of the study group were examined by enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression of both patients and controls were investigated by immunohistochemistry. RESULTS: Serum leptin levels, tissue leptin and leptin receptor expression were significantly higher in patients with severe psoriasis than patients with mild-moderate psoriasis and controls (P < 0.05). Serum leptin levels showed a positive correlation with Psoriasis Area and Severity Index and involved body surface area in patients with psoriasis. In addition, serum leptin levels, tissue leptin and leptin receptor expression showed a positive correlation with disease duration in patients with psoriasis (P < 0.01, r = 0.979; P < 0.01, r = 0.691; P < 0.01, r = 0.428, respectively). CONCLUSIONS: We assume that leptin might serve as a marker of severity in psoriasis and also may be a pathogenetic cofactor contributing to chronicity of the disease. Consequently, its role in obesity and cardiovascular disease in patients with psoriasis deserves to be studied. In addition, drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.

CD8+CD28-, suppressive T cells in systemic lupus erythematosus.

Recent studies show that a CD8+CD28- phenotype of T-cell population inhibits the reactivity of T-helper cells either by a contact-dependent mechanism or with secreting suppressive cytokines. In this study, we have explored the peripheral blood CD8+CD28- T-cell population in 53 patients with systemic lupus erythematosus (SLE) in comparison to healthy and diseased control groups. The distribution of CD28- cells within CD8+ population has been found significantly lower in patients with SLE than in healthy individuals. While there were no significant differences in the expression of costimulatory molecules CD80 and CD86, the CD40 expression on monocytes was found significantly lower and there was a slight decrease of expression of Interleukin-10 (IL-10) in CD8+CD28- population in patients with SLE. The Transforming growth factor-beta (TGF-beta) mRNA expression was found higher in CD8+CD28- T cells. Neither activation induced nor time-dependent change in the frequency of CD8+CD28- cells has been observed following stimulation at various time-points indicating that the control of CD28 expression was not dependent on the presence of sustained stimulations. Decrease in CD8+CD28- T cells which normally produce TGF-beta and their low-level IL-10 content may reflect impaired T-cell suppression and accordingly, increased T cell help to autoreactive B cells in patients with SLE.