Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome

Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. Results: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad TH1/TH2/TH17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by TH1 effector T cells. Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS

Detection of human chromosomes in somatic cell hybrids by PCR analysis

The detection of human chromosomes in somatic cell hybrids is usually made by chromosomal analysis, Southern blot analysis with human probes, and starch-gel electrophoresis of isoenzymes. We describe here a new, quick, and very efficient method to detect human chromosomes in somatic cell hybrids between human and rodent (rat and mouse) cells. The method is based on the polymerase chain reaction to promote amplification of human DNA, using primers derived from localized genes or DNA fragments from each human chromosome

Comparative performance of lab tests and blood testing device to monitor glucose, total cholesterol and triacylglycerol in type 2 diabetic patients

The performance of lab tests (LT) and blood testing devices (BTD) to monitor glycemia vs. glycated hemoglobin A1c (A1c) were compared. In addition, the performance of blood glucose, total cholesterol (TC) and triacylglycerol measured by LT and BDT were compared. All parameters were measured based on the same blood samples from overnight fasted type 2 diabetic patients (T2DP). Linear regression analysis was used for all comparisons. The results showed that A1c correlated better with LT-glucose (r = 0.58) than BTD-glucose (r = 0.42). Moreover, LT vs. BTD showed r values of 0.90, 0.82 and 0.92 for glucose, TC and triacylglycerol, respectively. It was concluded that the performance of LT-glucose was better than BDT-glucose. Moreover, since triacylycerol and TC measured by BTD correlated better with LT compared to BDT-glucose vs. LT-glucose, the inclusion of BTD-TC and BTD-triacylglycerol for detecting and monitoring hyperlipidemia in T2DP should be considered.Comparou-se a performance de avaliação da glicemia através de dosagens laboratoriais (DL) ou dispositivo para teste de sangue capilar (DTSC) vs. hemoglobina glicada A1c (A1c). Comparou-se ainda a performance de avaliação da glicemia, colesterol total (CT) e triacilglicerol (DL vs. DTSC). Avaliou-se estes parametros a partir das mesmas amostras de sangue coletadas em pacientes diabéticos tipo 2 (PDT2) em jejum noturno, sendo as comparações realizadas através de análise de regressão linear. A A1c correlacionou-se melhor com a glicemia-DL (r = 0,58) em relação a glicemia-DTSC (r = 0,42). Comparou-se DL vs. DTSC obtendo se r = 0,90, 0,82 e 0,92 para glicemia, CT e triacilglicerol, respectivamente. Concluiu-se que houve melhor performance da glicose-DL em relação a glicose-DTSC. Além disso, considerando que o triacilglicerol e TC avaliado através de DTSC correlaciona-se melhor com DL em comparação a DTSC-glicose vs. DL-glicose, a inclusão de DTSC-TC e DTSC-triacilglicerol visando detectar e monitorar hyperlipidemia in PDT2 deve ser considerada