12/21/2023 0 Comments Alpus autologic![]() Whole-exome sequencing (WES) and Sanger sequencing revealed two different essential splicing variations of an immune-related gene. We report three patients with MSMD from two consanguineous families, whose whole blood display normal responses to IFN-? and IL-12. Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, and the known genetic etiologies impair the IFN-?/IL-12 axis. Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, Ankara, TurkeyĥLaboratoire de Génétique Humaine des Maladies Infectieuses INSERM U1163, Institut Imagine, Paris, FranceĦDepartment of Biochemistry, McGill University, Montreal, CanadaħImmunology Program, Garvan Institute of Medical Research, Sydney, AustraliaĨCentre d'Etudes des Déficits Immunitaires (CEDI), Hôpital Necker Enfants-Malades, Paris, France ![]() King Hassan II University, Casablanca, MoroccoĤDepartment of Pediatric Immunology, Dr. Giles Laboratory of infectious disease, The Rockefeller University, New York, USAĢDivision of Immunology Infection and Inflammatory Diseases, King's College London Medical School, London, United KingdomģClinical Immmunology Unit, Medical School. ESID-0280 A New Genetic Disorder Predispose Mendelian Susceptibility to Mycobacterial Diseases Our results further suggest that human TIRAP-dependent TLR2 immunity is important for the control of staphylococcal infection in children lacking anti-LTA antibodies, but that TIRAP is otherwise redundant in host defense. We thus provide here the first description of human inherited TIRAP deficiency. The combined effect of inherited TIRAP deficiency and a lack of anti-LTA Abs therefore accounts for staphylococcal disease in this patient. This defective response was due to a lack of anti-LTA antibodies in the patient's plasma specific to the index case, and it was reversible by the addition of exogenous monoclonal anti-LTA Abs. However, the whole-blood response to staphylococcal lipoteichoic acid (LTA), another TLR2 agonist, was impaired only in the index case. Responses to the TLR2 agonists PAM2CSK4, PAM3CSK4, and FSL-1, and the TLR4 agonist lipopolysaccharide (LPS) were impaired in the fibroblasts, granulocytes and monocytes of all TIRAP-deficient individuals tested. The other seven individuals identified were adult relatives of the proband, aged between 16 and 50 years, who had never presented any serious infection. The four-year-old proband suffered from life-threatening staphylococcal pneumonia. These individuals are homozygous for a loss-of-function TIRAP allele. We describe here eight individuals with inherited deficiency of TIRAP (also called MAL), an adaptor acting downstream from TLR2 and TLR4. The human genetic basis of staphylococcal disease is largely unknown, but patients with inherited MyD88 or IRAK-4 deficiency are prone to staphylococcal disease. ![]() Puel 1ġHuman Genetics of Infectious Diseases, Imagine, PARIS, FranceĢRoyal Manchester Children’s Hospital, University of Manchester, Manchester, United Kingdom ESID-0092 Staphylococcal Disease in Humans with Inherited TIRAP/MAL Deficiency and Impaired Antibody Response to the TLR2 Agonist LTA
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