Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia
Zielen, Stefan (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Duecker, Ruth Pia (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Woelke, Sandra (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Donath, Helena (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Bakhtiar, Shahrzad (Goethe University. Division for Stem Cell Transplantation, Immunology and Intensive Care Unit)
Buecker, Aileen (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Kreyenberg, Hermann (Goethe University. Division for Stem Cell Transplantation, Immunology and Intensive Care Unit)
Huenecke, Sabine (Goethe University. Division for Stem Cell Transplantation, Immunology and Intensive Care Unit)
Bader, Peter (Goethe University. Division for Stem Cell Transplantation, Immunology and Intensive Care Unit)
Mahlaoui, Nizar (Necker Children's University Hospital. Pediatric Immunology-Hematology and Rheumatology Unit)
Ehl, Stephan (University of Freiburg. Institute for Immunodeficiency)
El-Helou, Sabine M. (Hannover Medical School. Department of Rheumatology and Immunology)
Pietrucha, Barbara (The Children's Memorial Health Institute. Department of Immunology)
Plebani, Alessandro (University of Brescia. Department of Clinical and Experimental Sciences)
van der Flier, Michiel (Radboud University Medical Center. Section Pediatric Infectious Diseases)
van Aerde, Koen (Radboud University Medical Center. Department of Pediatrics)
Kilic, Sara S. (Uludag University. Department of Pediatric Immunology and Rheumatology)
Reda, Shereen M. (Ain Shams University. Department of Pediatrics)
Kostyuchenko, Larysa (Western Ukrainian Specialized Children's Medical Centre)
McDermott, Elizabeth (Nottingham University Hospitals NHS Trust (Regne Unit))
Galal, Nermeen (Cairo University Specialized Pediatric Hospital. Department of Pediatrics)
Pignata, Claudio (Federico II University. Department of Translational Medical Sciences)
Santos-Pérez, Juan Luis (Hospital Universitario Virgen de las Nieves (Granada))
Laws, Hans-Juergen (Heinrich-Heine University. Department of Pediatric Oncology, Hematology and Clinical Immunology)
Niehues, Tim (Centre for Child and Adolescent Health (Krefeld, Germany))
Kutukculer, Necil (Ege University. Department of Pediatric Immunology)
Seidel, Markus G. (Medical University Graz. Department of Pediatrics and Adolescent Medicine)
Marques, Laura (Porto Hospital Center. Pediatric Department)
Ciznar, Peter (Comenius University in Bratislava. Pediatric Department)
Edgar, John David M. (The Royal Hospitals & Queen's University)
Soler-Palacín, Pere (Hospital Universitari Vall d'Hebron. Institut de Recerca)
von Bernuth, Horst (Charité - Universitätsmedizin Berlin)
Krueger, Renate (Charité - Universitätsmedizin Berlin)
Meyts, Isabelle (University Hospitals Leuven (Bèlgica))
Baumann, Ulrich (Hannover Medical School. Department of Paediatric Pulmonology, Allergy and Neonatology)
Kanariou, Maria ("Aghia Sophia" Children's Hospital. Department of Immunology and Histocompatibility)
Grimbacher, Bodo (Albert-Ludwigs University)
Hauck, Fabian (Ludwig-Maximilians-University Munich. Department of Pediatrics)
Graf, Dagmar (MVZ Dr. Reising-Ackermann Und Kollegen (Leipzig, Germany))
Granado, Luis Ignacio Gonzalez (Universidad Complutense de Madrid)
Prader, Seraina (University Children's Hospital Zurich. Division of Immunology and Children's Research Center)
Reisli, Ismail (Necmettin Erbakan University. Department of Pediatrics)
Slatter, Mary (Newcastle University. Primary Immunodeficiency Group, Paediatric Immunology and Haematopoietic Stem Cell Transplantation)
Rodríguez-Gallego, Carlos (University Fernando Pessoa Canarias. Department of Immunology)
Arkwright, Peter D. (University of Manchester. Lydia Becker Institute of Immunology and Inflammation)
Bethune, Claire (University Hospitals Plymouth NHS Trust (Regne Unit))
Deripapa, Elena (National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia))
Sharapova, Svetlana O. (Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. Research Department)
Lehmberg, Kai (University Medical Center Hamburg-Eppendorf. Division for Pediatric Stem Cell Transplantation and Immunology)
Davies, E. Graham (Great Ormond Street Hospital for Children (Londres))
Schuetz, Catharina (Technische Universität Dresden. Department of Pediatrics)
Kindle, Gerhard (University of Freiburg. FREEZE Biobank)
Schubert, Ralf (Goethe University. Division of Allergology, Pulmonology and Cystic Fibrosis)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Patients with ataxia-telangiectasia (A-T) sufer from progressive cerebellar ataxia, immunodefciency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA defciency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA defciency collected from the European Society for Immunodefciencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have signifcant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/ CD45RA) were signifcantly diminished compared to standard values. Patients with IgA defciency (n=35) had signifcantly lower lymphocyte counts compared to A-T patients without IgA defciency (n=31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed afected TCR-ß repertoires compared to controls, no diferences could be detected between patients with and without IgA defciency. Overall survival of patients with IgA defciency was signifcantly diminished. For the frst time, our data show that patients with IgA defciency have signifcantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA defciency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials. gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).
Ayudas:	European Commission 201549
Nota:	Altres ajuts: Open Access funding enabled and organized by Projekt DEAL.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Ataxia-telangiectasia ; IgA deficiency ; Immunoglobulins ; Immunodeficiency ; Lymphopenia ; Mortality
Publicado en:	Journal of Clinical Immunology, Vol. 41 (september 2021) , p. 1878-1892, ISSN 1573-2592

DOI: 10.1007/s10875-021-01090-8
PMID: 34477998

15 p, 3.0 MB

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