Prevalence of Inflammatory Pathways Over Immuno-Tolerance in Peripheral Blood Mononuclear Cells of Recent-Onset Type 1 Diabetes.

Background: Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms. Methods: We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls. Results: We identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data. Conclusions: Our analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.

Aspectos clínicos e neurorradiológicos do pseudo-hipoparatireoidismo: relato de caso / Clinical and neuroradiologic aspects of pseudohypoparathyreoidism: case report

Os autores relatam o caso de um paciente do sexo masculino, de 18 anos, com baixa estatura, epilepsia e deficiencia mental, alem de calcificacoes dos glanglios da base. Os achados clinicos e laboratorias sugeriram psdeudo-hipoparatireoidismo. Trata-se de patologia rara, de base genetica, secundaria a resistencia periferica ao hormonio da paratireoide e que evolui com excitabilidade neuromuscular, baixa estatura e calcificacoes dos glanglios da base, entre outros achados. Sao discutidas as formas de diagnosticas e a terapeutica empregada, seguidas de preve revisao da literatura sobre calcificacao dos glanglios da base.