Chronic granulomatous disease (CGD) is an inherited disorder caused by defects in the NADPH oxidase complex, which generates superoxide, the precursor of hydrogen peroxide (H(2)O(2)) and other reactive oxygen derivatives with microbicidal activity. Because CGD patients are at risk of chronic inflammatory manifestations, including inflammatory bowel disease and autoimmune diseases, and it is not clear whether these pathologies are exclusively secondary to altered superoxide production, or whether distinct immunologic defects are involved, we explored cell proliferation, lymphocyte cell counts, immunoglobulin levels, presence of autoimmune antibodies and expression of costimulatory molecules in leukocytes from CGD patients. We found that CGD patients have a diminished phytohemagglutinin-induced proliferation of blood mononuclear cells. Following stimulation with PMA plus ionomycin, a reduced percentage of CD40L expression in T lymphocytes and a diminished expression of CD40 molecules in neutrophils were observed on leukocytes from these patients. Our results suggest an altered interplay between elements of innate and adaptive immunity in CGD patients, which may be reflected in an increased susceptibility to opportunistic infections.

ObjectivesThis study aimed to investigate the clinical and prognostic relevance of the Hippo‐YAP transactivators YAP1 and TAZ in oral squamous cell carcinoma, and their possible relationship with PI3K/mTOR pathway activation.Materials and MethodsImmunohistochemical analysis of YAP1, TAZ, PIK3CA (p110α), p‐AKT (Ser473), and p‐S6 (Ser235) was performed in paraffin‐embedded tissue specimens from 165 OSCC patients. Correlations between protein expression and clinical data were further assessed.ResultsYAP1 expression was detected in both cytoplasm and nucleus of tumor cells, whereas TAZ expression was only found in the nucleus. Nuclear YAP1 was significantly associated with tumor size (p = 0.03), neck lymph node metastasis (p = 0.02), TNM stage (p = 0.02), and poor differentiation (p = 0.04). Nuclear TAZ was associated with tobacco (p = 0.03) and alcohol consumption (p = 0.04), and poor tumor differentiation (p = 0.04). There was a positive significant correlation between nuclear and cytoplasmic YAP1, nuclear TAZ, p110α expression, and mTORC1 activation p‐S6 (S235). Combined expression of nuclear and cytoplasmic YAP1 was prognostic in both univariate and multivariate analyses. Active nuclear YAP1 was significantly and independently associated with poor disease‐specific (p = 0.005, HR = 2.520; 95% CI = 1.319–4.816) and overall survival (p = 0.015, HR = 2.126; 95% CI = 1.155–3.916).ConclusionNuclear YAP1 is an independent predictor of poor survival in oral squamous cell carcinoma.

Background Previous studies suggest a link between CAG repeat number in the HTT gene and non‐Huntington neurodegenerative diseases. Objective The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α‐synucleinopathies or their behavior as modulators of the phenotype. Methods We genotyped the HTT gene CAG repeat number and APOE‐Ɛ isoforms in a case‐control series including patients with either clinical or neuropathological diagnosis of α‐synucleinopathy. Results We identified three Parkinson's disease (PD) patients (0.30%) and two healthy controls (0.19%) carrying low‐penetrance HTT repeat expansions whereas none of the dementia with Lewy bodies (DLB) or multisystem atrophy (MSA) patients carried pathogenic HTT expansions. In addition, a clear increase in the number of HTT CAG repeats was found among DLB and PD groups influenced by the male gender and also by the APOE4 allele among DLB patients. HTT intermediate alleles' (IAs) distribution frequency increased in the MSA group compared with controls (8.8% vs. 3.9%, respectively). These differences were indeed statistically significant in the MSA group with neuropathological confirmation. Two MSA HTT CAG IAs carriers with 32 HTT CAG repeats showed isolated polyQ inclusions in pons and basal nuclei, which are two critical structures in the neurodegeneration of MSA. Conclusions Our results point to a link between HTT CAG number, HTT IAs, and expanded HTT CAG repeats with other non‐HD brain pathology and support the hypothesis that they can share common neurodegenerative pathways. © 2022 International Parkinson and Movement Disorder Society.

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