Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia.

Adolescent Adult Ataxia Telangiectasia / immunology B-Lymphocytes / immunology Child Child, Preschool Female Humans IgA Deficiency / immunology IgG Deficiency / immunology Immunoglobulin A / blood Immunoglobulin G / blood Immunoglobulin M / blood Infant Lymphocyte Count Male Middle Aged T-Lymphocyte Subsets / immunology Young Adult
Ataxia-telangiectasia IgA deficiency Immunodeficiency Immunoglobulins Lymphopenia Mortality

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
11 2021
Historique:
received: 28 01 2021
accepted: 25 06 2021
pubmed: 4 9 2021
medline: 19 2 2022
entrez: 3 9 2021
Statut: ppublish

Résumé

Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency 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 deficiency collected from the European Society for Immunodeficiencies (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 significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (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 affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. 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).

Identifiants

DOI: 10.1007/s10875-021-01090-8 PMID: 34477998 PMC: PMC8604875
pubmed: 34477998
doi: 10.1007/s10875-021-01090-8
pii: 10.1007/s10875-021-01090-8
pmc: PMC8604875
doi:

Substances chimiques

Immunoglobulin A 0
Immunoglobulin G 0
Immunoglobulin M 0

Banques de données

ClinicalTrials.gov
['NCT03357978', 'NCT02345135']

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1878-1892

Subventions

Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© 2021. The Author(s).

Références

Boder E, Sedgwick RP. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 1958;21:526–54.
pubmed: 13542097
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016;11:159. https://doi.org/10.1186/s13023-016-0543-7 .
doi: 10.1186/s13023-016-0543-7 pubmed: 27884168 pmcid: 5123280
Schroeder SA, Zielen S. Infections of the respiratory system in patients with ataxia-telangiectasia. Pediatr Pulmonol. 2014;49:389–99. https://doi.org/10.1002/ppul.22817 .
doi: 10.1002/ppul.22817 pubmed: 23761391
Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D. Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. Pediatr Res. 2016;79:889–94. https://doi.org/10.1038/pr.2016.19 .
doi: 10.1038/pr.2016.19 pubmed: 26891003
Pommerening H, van Dullemen S, Kieslich M, Schubert R, Zielen S, Voss S. Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study. Orphanet J Rare Dis. 2015;10:155. https://doi.org/10.1186/s13023-015-0373-z .
doi: 10.1186/s13023-015-0373-z pubmed: 26645295 pmcid: 4673730
Schubert R, Reichenbach J, Zielen S. Growth factor deficiency in patients with ataxia telangiectasia. Clin Exp Immunol. 2005;140:517–9. https://doi.org/10.1111/j.1365-2249.2005.02782.x .
doi: 10.1111/j.1365-2249.2005.02782.x pubmed: 15932513 pmcid: 1809398
Voss S, Pietzner J, Hoche F, Taylor AMR, Last JI, Schubert R, Zielen S. Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia. Growth Factors. 2014;32:123–9. https://doi.org/10.3109/08977194.2014.939805 .
doi: 10.3109/08977194.2014.939805 pubmed: 25060036
Donath H, Woelke S, Theis M, Heß U, Knop V, Herrmann E, et al. Progressive liver disease in patients with ataxia telangiectasia. Front Pediatr. 2019;7:458. https://doi.org/10.3389/fped.2019.00458 .
doi: 10.3389/fped.2019.00458 pubmed: 31788461 pmcid: 6856634
Micol R, Ben Slama L, Suarez F, Le Mignot L, Beauté J, Mahlaoui N, et al. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. 2011;128:382-9.e1. https://doi.org/10.1016/j.jaci.2011.03.052 .
doi: 10.1016/j.jaci.2011.03.052 pubmed: 21665257
Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004;144:505–11. https://doi.org/10.1016/j.jpeds.2003.12.046 .
doi: 10.1016/j.jpeds.2003.12.046 pubmed: 15069401
Schubert R, Reichenbach J, Zielen S. Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia. Clin Exp Immunol. 2002;129:125–32. https://doi.org/10.1046/j.1365-2249.2002.01830.x .
doi: 10.1046/j.1365-2249.2002.01830.x pubmed: 12100032 pmcid: 1906431
Reichenbach J, Schubert R, Feinberg J, Beck O, Rosewich M, Rose MA, Zielen S. Impaired interferon-gamma production in response to live bacteria and Toll-like receptor agonists in patients with ataxia telangiectasia. Clin Exp Immunol. 2006;146:381–9. https://doi.org/10.1111/j.1365-2249.2006.03221.x .
doi: 10.1111/j.1365-2249.2006.03221.x pubmed: 17100756 pmcid: 1810411
Schubert R, Reichenbach J, Rose M, Zielen S. Immunogenicity of the seven valent pneumococcal conjugate vaccine in patients with ataxia-telangiectasia. Pediatr Infect Dis J. 2004;23:269–70.
doi: 10.1097/01.inf.0000115737.35353.55
Driessen GJ, Ijspeert H, Weemaes CMR, Haraldsson Á, Trip M, Warris A, et al. Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J Allergy Clin Immunol. 2013;131:1367-75.e9. https://doi.org/10.1016/j.jaci.2013.01.053 .
doi: 10.1016/j.jaci.2013.01.053 pubmed: 23566627
Giovannetti A, Mazzetta F, Caprini E, Aiuti A, Marziali M, Pierdominici M, et al. Skewed T-cell receptor repertoire, decreased thymic output, and predominance of terminally differentiated T cells in ataxia telangiectasia. Blood. 2002;100:4082–9. https://doi.org/10.1182/blood-2002-03-0976 .
doi: 10.1182/blood-2002-03-0976 pubmed: 12393664
Bagley J, Singh G, Iacomini J. Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation. J Immunol. 2007;178:4757–63. https://doi.org/10.4049/jimmunol.178.8.4757 .
doi: 10.4049/jimmunol.178.8.4757 pubmed: 17404255
Matei IR, Gladdy RA, Nutter LMJ, Canty A, Guidos CJ, Danska JS. ATM deficiency disrupts Tcra locus integrity and the maturation of CD4+CD8+ thymocytes. Blood. 2007;109:1887–96. https://doi.org/10.1182/blood-2006-05-020917 .
doi: 10.1182/blood-2006-05-020917 pubmed: 17077325
Carney EF, Srinivasan V, Moss PA, Taylor AM. Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95. J Immunol. 2012;189:261–8. https://doi.org/10.4049/jimmunol.1101909 .
doi: 10.4049/jimmunol.1101909 pubmed: 22649200
van Os NJH, Jansen AFM, van Deuren M, Haraldsson A, van Driel NTM, Etzioni A, et al. Ataxia-telangiectasia: immunodeficiency and survival. Clin Immunol. 2017;178:45–55. https://doi.org/10.1016/j.clim.2017.01.009 .
doi: 10.1016/j.clim.2017.01.009 pubmed: 28126470
Verhagen MMM, Last JI, Hogervorst FBL, Smeets DFCM, Roeleveld N, Verheijen F, et al. Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study. Hum Mutat. 2012;33:561–71. https://doi.org/10.1002/humu.22016 .
doi: 10.1002/humu.22016 pubmed: 22213089
Ambrose M, Gatti RA. Pathogenesis of ataxia-telangiectasia: The next generation of ATM functions. Blood. 2013;121:4036–45. https://doi.org/10.1182/blood-2012-09-456897 .
doi: 10.1182/blood-2012-09-456897 pubmed: 23440242 pmcid: 3709651
Barlow C, Dennery PA, Shigenaga MK, Smith MA, Morrow JD, Roberts LJ, et al. Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc Natl Acad Sci U S A. 1999;96:9915–9. https://doi.org/10.1073/pnas.96.17.9915 .
doi: 10.1073/pnas.96.17.9915 pubmed: 10449794 pmcid: 22310
Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004;431:997–1002. https://doi.org/10.1038/nature02989 .
doi: 10.1038/nature02989 pubmed: 15496926
Reichenbach J, Schubert R, Schindler D, Müller K, Böhles H, Zielen S. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid Redox Signal. 2002;4:465–9. https://doi.org/10.1089/15230860260196254 .
doi: 10.1089/15230860260196254 pubmed: 12215213
Barlow C, Eckhaus MA, Schäffer AA, Wynshaw-Boris A. Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice. Nat Genet. 1999;21:359–60. https://doi.org/10.1038/7684 .
doi: 10.1038/7684 pubmed: 10192382
Woelke S, Valesky E, Bakhtiar S, Pommerening H, Pfeffermann LM, Schubert R, Zielen S. Treatment of granulomas in patients with ataxia telangiectasia. Front Immunol. 2018;9:2000. https://doi.org/10.3389/fimmu.2018.02000 .
doi: 10.3389/fimmu.2018.02000 pubmed: 30279689 pmcid: 6153364
Krauthammer A, Lahad A, Goldberg L, Sarouk I, Weiss B, Somech R, et al. Elevated IgM levels as a marker for a unique phenotype in patients with Ataxia telangiectasia. BMC Pediatr. 2018;18:185. https://doi.org/10.1186/s12887-018-1156-1 .
doi: 10.1186/s12887-018-1156-1 pubmed: 29866155 pmcid: 5987459
Mohammadinejad P, Abolhassani H, Aghamohammadi A, Pourhamdi S, Ghosh S, Sadeghi B, et al. Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM. J Immunoassay Immunochem. 2015;36:16–26. https://doi.org/10.1080/15321819.2014.891525 .
doi: 10.1080/15321819.2014.891525 pubmed: 24568663
Folgori L, Scarselli A, Angelino G, Ferrari F, Antoccia A, Chessa L, Finocchi A. Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: A case report. Ital J Pediatr. 2010;36:29. https://doi.org/10.1186/1824-7288-36-29 .
doi: 10.1186/1824-7288-36-29 pubmed: 20380744 pmcid: 2857855
van Os NJH, Chessa L, Weemaes CMR, van Deuren M, Fiévet A, van Gaalen J, et al. Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576GA and c.8147TC mutations. J Med Genet. 2019;56:308–16. https://doi.org/10.1136/jmedgenet-2018-105635 .
doi: 10.1136/jmedgenet-2018-105635 pubmed: 30819809
Ludvigsson JF, Neovius M, Hammarström L. Risk of Infections Among 2100 Individuals with IgA deficiency: a nationwide cohort study. J Clin Immunol. 2016;36:134–40. https://doi.org/10.1007/s10875-015-0230-9 .
doi: 10.1007/s10875-015-0230-9 pubmed: 26739713
Weber-Mzell D, Kotanko P, Hauer AC, Goriup U, Haas J, Lanner N, et al. Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians. Eur J Clin Invest. 2004;34:224–8. https://doi.org/10.1111/j.1365-2362.2004.01311.x .
doi: 10.1111/j.1365-2362.2004.01311.x pubmed: 15025682
Bakhtiar S, Woelke S, Huenecke S, Kieslich M, Taylor AM, Schubert R, et al. Pre-emptive allogeneic hematopoietic stem cell transplantation in ataxia telangiectasia. Front Immunol. 2018;9:2495. https://doi.org/10.3389/fimmu.2018.02495 .
doi: 10.3389/fimmu.2018.02495 pubmed: 30420857 pmcid: 6215822
Shannon CE. The mathematical theory of communication. 1963. MD Comput. 1997;14:306–17.
pubmed: 9230594
O’Connell AE, Volpi S, Dobbs K, Fiorini C, Tsitsikov E, de Boer H, et al. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome. Front Immunol. 2014;5:340. https://doi.org/10.3389/fimmu.2014.00340 .
doi: 10.3389/fimmu.2014.00340 pubmed: 25101082 pmcid: 4102881
Leuzzi V, Micheli R, D’Agnano D, Molinaro A, Venturi T, Plebani A, et al. Positive effect of erythrocyte-delivered dexamethasone in ataxia-telangiectasia. Neurol Neuroimmunol Neuroinflamm. 2015;2: e98. https://doi.org/10.1212/NXI.0000000000000098 .
doi: 10.1212/NXI.0000000000000098 pubmed: 25884015 pmcid: 4396528
Zielen S, Schubert R. Workshop report: European workshop on ataxia-telangiectasia, Frankfurt, 2011. J Neurogenet. 2011;25:78–81. https://doi.org/10.3109/01677063.2011.592553 .
doi: 10.3109/01677063.2011.592553 pubmed: 21732725
Sanal O, Ersoy F, Yel L, Tezcan I, Metin A, Ozyürek H, et al. Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia. J Clin Immunol. 1999;19:326–34. https://doi.org/10.1023/a:1020599810261 .
doi: 10.1023/a:1020599810261 pubmed: 10535610
Panchakshari RA, Zhang X, Kumar V, Du Z, Wei P-C, Kao J, et al. DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions. Proc Natl Acad Sci U S A. 2018;115:762–7. https://doi.org/10.1073/pnas.1719988115 .
doi: 10.1073/pnas.1719988115 pubmed: 29311308 pmcid: 5789958
Amirifar P, Mozdarani H, Yazdani R, Kiaei F, Moeini Shad T, Shahkarami S, et al. Effect of class switch recombination defect on the phenotype of ataxia-telangiectasia Patients. Immunol Invest. 2020:1–15. https://doi.org/10.1080/08820139.2020.1723104 .
Yazdani R, Latif A, Tabassomi F, Abolhassani H, Azizi G, Rezaei N, Aghamohammadi A. Clinical phenotype classification for selective immunoglobulin A deficiency. Expert Rev Clin Immunol. 2015;11:1245–54. https://doi.org/10.1586/1744666X.2015.1081565 .
doi: 10.1586/1744666X.2015.1081565 pubmed: 26306496
Breedveld A, van Egmond M. IgA and FcαRI: pathological roles and therapeutic opportunities. Front Immunol. 2019;10:553. https://doi.org/10.3389/fimmu.2019.00553 .
doi: 10.3389/fimmu.2019.00553 pubmed: 30984170 pmcid: 6448004
Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffié C, et al. Identification of FcalphaRI as an inhibitory receptor that controls inflammation: Dual role of FcRgamma ITAM. Immunity. 2005;22:31–42. https://doi.org/10.1016/j.immuni.2004.11.017 .
doi: 10.1016/j.immuni.2004.11.017 pubmed: 15664157
Bagheri Y, Sanaei R, Yazdani R, Shekarabi M, Falak R, Mohammadi J, et al. The Heterogeneous pathogenesis of selective immunoglobulin a deficiency. Int Arch Allergy Immunol. 2019;179:231–46. https://doi.org/10.1159/000499044 .
doi: 10.1159/000499044 pubmed: 31091523
Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: Function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–63. https://doi.org/10.1146/annurev.immunol.22.012703.104702 .
doi: 10.1146/annurev.immunol.22.012703.104702 pubmed: 15032595
Ramiscal RR, Vinuesa CG. T-cell subsets in the germinal center. Immunol Rev. 2013;252:146–55. https://doi.org/10.1111/imr.12031 .
doi: 10.1111/imr.12031 pubmed: 23405902
Amiezer M, Phan TG. Disentangling Tfr cells from Treg cells and Tfh cells: how to untie the Gordian knot. Eur J Immunol. 2016;46:1101–4. https://doi.org/10.1002/eji.201646389 .
doi: 10.1002/eji.201646389 pubmed: 27109022
Morio T, Takahashi N, Watanabe F, Honda F, Sato M, Takagi M, et al. Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan. Int J Hematol. 2009;90:455–62. https://doi.org/10.1007/s12185-009-0408-0 .
doi: 10.1007/s12185-009-0408-0 pubmed: 19705055
Soresina A, Meini A, Lougaris V, Cattaneo G, Pellegrino S, Piane M, et al. Different clinical and immunological presentation of ataxia-telangiectasia within the same family. Neuropediatrics. 2008;39:43–5. https://doi.org/10.1055/s-2008-1076736 .
doi: 10.1055/s-2008-1076736 pubmed: 18504682
Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, et al. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia. Eur Respir Rev. 2015;24:565–81. https://doi.org/10.1183/16000617.0066-2015 .
doi: 10.1183/16000617.0066-2015 pubmed: 26621971
Notarangelo LD, Fischer A, Geha RS, Casanova J-L, Chapel H, Conley ME, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124:1161–78. https://doi.org/10.1016/j.jaci.2009.10.013 .
doi: 10.1016/j.jaci.2009.10.013 pubmed: 20004777 pmcid: 2797319
Schon K, van Os NJH, Oscroft N, Baxendale H, Scoffings D, Ray J, et al. Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia. Ann Neurol. 2019;85:170–80. https://doi.org/10.1002/ana.25394 .
doi: 10.1002/ana.25394 pubmed: 30549301 pmcid: 6590299

Auteurs

Stefan Zielen (S)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Ruth Pia Duecker (RP)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany. RuthPia.Duecker@kgu.de.

Sandra Woelke (S)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Helena Donath (H)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Sharhzad Bakhtiar (S)

Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Aileen Buecker (A)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Hermann Kreyenberg (H)

Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Sabine Huenecke (S)

Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Peter Bader (P)

Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Nizar Mahlaoui (N)

Pediatric Immunology-Hematology and Rheumatology Unit, French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Children's University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Stephan Ehl (S)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Sabine M El-Helou (SM)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
RESIST - Cluster of Excellence 2155 To Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.

Barbara Pietrucha (B)

Department of Immunology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730, Warsaw, Poland.

Alessandro Plebani (A)

Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy.

Michiel van der Flier (M)

Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Koen van Aerde (K)

Department of Pediatrics, Amalia's Children Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.

Sara S Kilic (SS)

Department of Pediatric Immunology and Rheumatology, the School of Medicine, Uludag University, Bursa, Turkey.

Shereen M Reda (SM)

Department of Pediatrics, Children's Hospital, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Larysa Kostyuchenko (L)

Center of Pediatric Immunology, Western Ukrainian Specialized Children's Medical Centre, Lviv, Ukraine.

Elizabeth McDermott (E)

Clinical Immunology and Allergy Unit, Nottingham University Hospitals, Nottingham, UK.

Nermeen Galal (N)

Department of Pediatrics, Cairo University Specialized Pediatric Hospital, Cairo, Egypt.

Claudio Pignata (C)

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.

Juan Luis Santos Pérez (JLS)

Infectious Diseases and Immunodeficiencies Unit, Service of Pediatrics, Hospital Universitario Virgen de Las Nieves, Granada, Spain.

Hans-Juergen Laws (HJ)

Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine University, Duesseldorf, Germany.

Tim Niehues (T)

Centre for Child and Adolescent Health, Helios Klinikum Krefeld, Krefeld, Germany.

Necil Kutukculer (N)

Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey.

Markus G Seidel (MG)

Research Unit for Pediatric Hematology and Immunology, Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Laura Marques (L)

Pediatric Department, Infectious Diseases and Immunodeficiencies Unit, Porto Hospital Center, Porto, Portugal.

Peter Ciznar (P)

Pediatric Department, Faculty of Medicine, Children University Hospital in Bratislava, Comenius University in Bratislava, Bratislava, Slovakia.

John David M Edgar (JDM)

The Royal Hospitals & Queen's University, Belfast, UK.

Pere Soler-Palacín (P)

Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall D'Hebron Research Institute, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.

Horst von Bernuth (H)

Department of Pediatric Pneumology, Immunology and Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Immunology, Labor Berlin Charité - Vivantes GmbH, Berlin, Germany.
Berlin Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Renate Krueger (R)

Department of Pediatric Pneumology, Immunology and Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Isabelle Meyts (I)

Department of Pediatrics, University Hospitals Leuven, and the Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Ulrich Baumann (U)

Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.

Maria Kanariou (M)

Department of Immunology and Histocompatibility, Centre for Primary Immunodeficiencies, "Aghia Sophia" Children's Hospital, Athens, Greece.

Bodo Grimbacher (B)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
RESIST - Cluster of Excellence 2155 To Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
DZIF-German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany.

Fabian Hauck (F)

Department of Pediatrics, Dr. Von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.

Dagmar Graf (D)

MVZ Dr. Reising-Ackermann Und Kollegen, Leipzig, Germany.

Luis Ignacio Gonzalez Granado (LIG)

Primary Immunodeficiencies Unit, Pediatrics, Hospital 12 Octubre, Complutense University School of Medicine, Madrid, Spain.

Seraina Prader (S)

Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.

Ismail Reisli (I)

Department of Pediatrics, Division of Pediatric Immunology and Allergy, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.

Mary Slatter (M)

Primary Immunodeficiency Group, Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Translational and Clinical Research Institute, Great North Childrens' Hospital, Newcastle University, Newcastle upon Tyne, UK.

Carlos Rodríguez-Gallego (C)

Department of Immunology, Dr. Negrin University Hospital of Gran Canaria, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.

Peter D Arkwright (PD)

Lydia Becker Institute of Immunology and Inflammation, University of Manchester and Royal Manchester Children's Hospital, Manchester, UK.

Claire Bethune (C)

University Hospital Plymouth NHS Trust, Plymouth, UK.

Elena Deripapa (E)

National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Svetlana O Sharapova (SO)

Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Minsk, Belarus.

Kai Lehmberg (K)

Division for Pediatric Stem Cell Transplantation and Immunology, Clinic for Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

E Graham Davies (EG)

Great Ormond Street Hospital and UCL Great Ormond Street Institute of Child Health, London, UK.

Catharina Schuetz (C)

Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Gerhard Kindle (G)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
FREEZE Biobank, Center for Biobanking, Medical Center and Faculty of Medicine, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Ralf Schubert (R)

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Maladies d'immunodéficience primaire › Ataxie-télangiectasie › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Dysgammaglobulinémie › Déficit en IgA › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Dysgammaglobulinémie › Déficit en IgG › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline A › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline M › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémogramme › Numération des leucocytes › Numération des lymphocytes › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Simple Measurement of IgA Predicts Immunity...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › Simple Measurement of IgA Predicts Immunity...