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Abstract: Hereditary hemochromatosis (HH) is a genetic iron overload disease, in the majority of cases associated with homozygosity for the C282Y mutation of the HFE gene. In spite of this genetic homogeneity, there is a great clinical heterogeneity among HH patients. Low CD8+ lymphocyte numbers have been associated with a more severe expression of iron overload in HH patients, and in experimental models of iron overload. HH patients present low serum transferrin levels. Transferrin is an indispensable resource for lymphopoiesis. Lymphocyte homeostasis follows general ecology rules of population dynamics that involve competition for limiting resources. In the present study, we questioned whether transferrin levels could be associated with the anomalies seen previously in lymphocyte subset numbers in HH patients. Transferrin levels, total and subset T lymphocyte counts were done in 426 apparently healthy subjects genotyped for HFE. All HFE C282Y carriers presented significantly lower serum transferrin levels than the wild type group, a difference that could not be explained solely by the degree of iron overload. Significant differences were also seen in transferrin levels between males and females, with females presenting higher average serum Transferrin levels. In the population of subjects with Transferrin levels lower than 248 mg/dl, a positive correlation was seen between the peripheral CD8+ lymphocyte numbers and serum transferrin levels (R 2 = 2.41; r = 0.16; P = 0.018). To test the possible limiting resource effect of transferrin, the correlation between transferrin levels and CD8+ lymphocyte numbers was scrutinized in 34 HH patients, homozygous for the C282Y mutation. In the homozygous males, where the lowest average transferrin levels were seen, another highly significant correlation was observed between Transferrin levels and CD8+ numbers. This correlation points to a possible role of transferrin as a limiting resource for MHC class I dependent lymphocyte proliferation, an effect that was not observed in C282Y homozygous female patients. [Copyright &y& Elsevier]

In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω −3 LCPUFAs group than placebo at month six of supplementation. FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research. [ABSTRACT FROM AUTHOR]

Background: Quality of the nucleic acids extracted from Formalin Fixed Paraffin Embedded (FFPE) samples largely depends on pre-analytic, fixation and storage conditions. We assessed the differential sensitivity of viral and human double stranded DNA (dsDNA) to degradation with storage time., Methods: We randomly selected forty-four HPV16-positive invasive cervical cancer (ICC) FFPE samples collected between 1930 and 1935 and between 2000 and 2004. We evaluated through qPCR the amplification within the same sample of two targets of the HPV16 L1 gene (69 bp, 134 bp) compared with two targets of the human tubulin-β gene (65 bp, 149 bp)., Results: Both viral and human, short and long targets were amplified from all samples stored for 15 years. In samples archived for 85 years, we observed a significant decrease in the ability to amplify longer targets and this difference was larger in human than in viral DNA: longer fragments were nine times (CI 95% 2.6-35.2) less likely to be recovered from human DNA compared with 1.6 times (CI 95% 1.1-2.2) for viral DNA., Conclusions: We conclude that human and viral DNA show a differential decay kinetics in FFPE samples. The faster degradation of human DNA should be considered when assessing viral DNA prevalence in long stored samples, as HPV DNA detection remains a key biomarker of viral-associated transformation.

Newborn was referred with diagnosis of neonatal epilepsy. Medical team could suspect and confirm D-bifunctional peroxisomal enzymatic deficiency diagnosis. It was made by family antecedents, severe neonatal hypotonia, uncontrolled neonatal seizures, craniofacial dysmorphic features, psychomotor retardation, neuronal migration defect and a positive peroxisomal panel. The full study in skin fibroblasts involved enzyme analysis, complementation studies and DNA analysis. The accumulation of very long chain fatty acids, partial deficiency in phytanic acid oxidation, and abnormal morphology of peroxisomes was consistent with a defect in peroxisomal fatty acid oxidation, involving D-bifunctional protein. It is very important to make a diagnosis of this innate error of metabolism in order to give preconceptional genetic counseling, to identify recurrence risk and to perform mutation analysis for the D-bifunctional protein gene, and to offer the prenatal diagnosis.