Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment

Antimicrobial peptides as an alternative to anti-tuberculosis drugs

Tuberculosis (TB) presently accounts for high global mortality and morbidity rates, despite the introduction four decades ago of the affordable and efficient four-drugs (isoniazid, rifampicin, pyrazinamide and ethambutol). Thus, a strong need exists for new drugs with special structures and uncommon modes of action to effectively overcome M. tuberculosis. Within this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that comprise a section of the innate immune system, are currently the leading potential agents for the treatment of TB. Many studies have recently illustrated the capability of anti-mycobacterial peptides to disrupt the normal mycobacterial cell wall function through various modes, thereby interacting with the intracellular targets, as well as encompassing nucleic acids, enzymes and organelles. This review presents a wide array of antimicrobial activities, alongside the associated properties of the AMPs that could be utilized as potential agents in therapeutic tactics for TB treatment

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment

Potentiation effect of the AMPK activator A-769662 on cardiac myocytes metabolism and survival

Abstract 286 van Poster session 2 Frontiers in CardioVascular Biology, London 30th March – 1st April 2012 Second Congress of the ESC Council on Basic Cardiovascular Science