Abatacept is useful in autoimmune cytopenia with immunopathologic manifestations caused by CTLA-4 defects

Abstract

Letter to Blood| January 13, 2022 Abatacept is useful in autoimmune cytopenia with immunopathologic manifestations caused by CTLA-4 defects Clinical Trials & Observations C. Dhunputh, C. Dhunputh Pediatric Hemato-Immunology Centre d'Investigation Clinique (CIC) 1401, INSERM Plurithématique CIC (CICP), Bordeaux University Hospital, Bordeaux, France;Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), Bordeaux University Hospital, Bordeaux, France; Search for other works by this author on: This Site PubMed Google Scholar S. Ducassou, S. Ducassou Pediatric Hemato-Immunology Centre d'Investigation Clinique (CIC) 1401, INSERM Plurithématique CIC (CICP), Bordeaux University Hospital, Bordeaux, France;Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), Bordeaux University Hospital, Bordeaux, France; Search for other works by this author on: This Site PubMed Google Scholar H. Fernandes, H. Fernandes Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), Bordeaux University Hospital, Bordeaux, France; Search for other works by this author on: This Site PubMed Google Scholar Capucine Picard, Capucine Picard Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique–Hôpitaux de Paris (AP-HP), University of Paris, Paris, France;Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine, Unite Mixte de Recherche (UMR) 1163, INSERM, Paris, France; https://orcid.org/0000-0001-8788-5056 Search for other works by this author on: This Site PubMed Google Scholar Frédéric Rieux-Laucat, Frédéric Rieux-Laucat Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine, Unite Mixte de Recherche (UMR) 1163, INSERM, Paris, France; https://orcid.org/0000-0001-7858-7866 Search for other works by this author on: This Site PubMed Google Scholar J.-F. Viallard, J.-F. Viallard Department of Internal Medicine and Infectious Diseases, Bordeaux University Hospital, Bordeaux, France; https://orcid.org/0000-0001-7500-9323 Search for other works by this author on: This Site PubMed Google Scholar E. Lazaro, E. Lazaro Department of Internal Medicine and Infectious Diseases, Bordeaux University Hospital, Bordeaux, France; Search for other works by this author on: This Site PubMed Google Scholar O. Hermine, O. Hermine Hematology Unit, Necker-Enfants Malades University Hospital, AP-HP, Paris, France; Search for other works by this author on: This Site PubMed Google Scholar M. Jouvray, M. Jouvray Department of Internal Medicine, Hospital of Arras, Arras, France; Search for other works by this author on: This Site PubMed Google Scholar I. Machelard, I. Machelard Department of Internal Medicine, Hospital of Bayonne, Bayonne, France; Search for other works by this author on: This Site PubMed Google Scholar A. Lambilliotte, A. Lambilliotte Department of Pediatric Hematology, Lille University Hospital, Lille, France; Search for other works by this author on: This Site PubMed Google Scholar M. Malphettes, M. Malphettes Clinical Immunology Department, Saint Louis University Hospital, AP-HP, Paris, France; Search for other works by this author on: This Site PubMed Google Scholar D. Moshous, D. Moshous Pediatric Immuno-Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France; Search for other works by this author on: This Site PubMed Google Scholar B. Neven, B. Neven Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine, Unite Mixte de Recherche (UMR) 1163, INSERM, Paris, France;Pediatric Immuno-Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France; Search for other works by this author on: This Site PubMed Google Scholar A. Gauthier, A. Gauthier Pediatric Hematology and Oncology Institut, Hospices Civils de Lyon, Lyon, France;Laboratoire Interuniversitaire de Biologie de la Motricité, EA7424, Team Vascular Biology and Red Blood Cell, University Claude Bernard Lyon 1, University of Lyon, Lyon, France; Search for other works by this author on: This Site PubMed Google Scholar N. Garnier, N. Garnier Pediatric Hematology and Oncology Institut, Hospices Civils de Lyon, Lyon, France; Search for other works by this author on: This Site PubMed Google Scholar T. Leblanc, T. Leblanc Pediatric Hematology and Immunology Department, Robert Debré University Hospital, AP-HP, Paris, France; and Search for other works by this author on: This Site PubMed Google Scholar J. Landman-Parker, J. Landman-Parker Pediatric Oncology Immunology Hematology Unit, Armand-Trousseau University Hospital, AP-HP, Paris, France Search for other works by this author on: This Site PubMed Google Scholar G. Leverger, G. Leverger Pediatric Oncology Immunology Hematology Unit, Armand-Trousseau University Hospital, AP-HP, Paris, France Search for other works by this author on: This Site PubMed Google Scholar N. Aladjidi N. Aladjidi Pediatric Hemato-Immunology Centre d'Investigation Clinique (CIC) 1401, INSERM Plurithématique CIC (CICP), Bordeaux University Hospital, Bordeaux, France;Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), Bordeaux University Hospital, Bordeaux, France; https://orcid.org/0000-0003-0231-4460 Search for other works by this author on: This Site PubMed Google Scholar Blood (2022) 139 (2): 300–304. https://doi.org/10.1182/blood.2021013496 Article history Submitted: July 28, 2021 Accepted: October 1, 2021 First Edition: October 29, 2021 Connected Content This is a related article to: Monogenically driven therapies: the new first line Share Icon Share Twitter LinkedIn Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation C. Dhunputh, S. Ducassou, H. Fernandes, Capucine Picard, Frédéric Rieux-Laucat, J.-F. Viallard, E. Lazaro, O. Hermine, M. Jouvray, I. Machelard, A. Lambilliotte, M. Malphettes, D. Moshous, B. Neven, A. Gauthier, N. Garnier, T. Leblanc, J. Landman-Parker, G. Leverger, N. Aladjidi; Abatacept is useful in autoimmune cytopenia with immunopathologic manifestations caused by CTLA-4 defects. Blood 2022; 139 (2): 300–304. doi: https://doi.org/10.1182/blood.2021013496 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Clinical Trials and Observations, Immunobiology and Immunotherapy, Platelets and Thrombopoiesis, Red Cells, Iron, and Erythropoiesis TO THE EDITOR: Autoimmune diseases can reveal underlying primary immune deficiencies (PIDs), among which are cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) pathway variants. From 2015, this pathway has become a classical clinical entity combining autoimmune cytopenia (AIC) and various immunopathologic manifestations (IMs).1,2 The role of CTLA-4 in controlling lymphocyte activation can be disrupted in case of dominant heterozygous CTLA-4 variants,3,4 recessive homozygous mutations, or deletions of lipopolysaccharide-responsive beige-like anchor (LRBA)5,6 or DEF6 variants.7 Abatacept, a CTLA-4 fusion protein labeled in rheumatoid arthritis,8 is a logical targeted option for those patients. In 2019, a preliminary study of the French OBS'CEREVANCE cohort of children with AIC identified CTLA-4 pathway pathogenic variants in 10 of 80 cases of pediatric-onset Evans syndrome (pES).9 pES is now recognized as a severe long-lasting disease: numerous IMs appearing with increasing age in... REFERENCES 1.Lo B, Fritz JM, Su HC, Uzel G, Jordan MB, Lenardo MJ. CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency. Blood. 2016;128(8):1037-1042.Google ScholarCrossrefSearch ADS PubMed 2.Gámez-Díaz L, Seidel MG. Different apples, same tree: visualizing current biological and clinical insights into CTLA-4 insufficiency and LRBA and DEF6 deficiencies. Front Pediatr. 2021;9:662645.Google ScholarCrossrefSearch ADS PubMed 3.Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345(6204):1623-1627.Google ScholarCrossrefSearch ADS PubMed 4.Schubert D, Bode C, Kenefeck R, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20(12):1410-1416.Google ScholarCrossrefSearch ADS PubMed 5.Moser von Filseck J, Čopič A, Delfosse V, et al. Intracellular transport. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate. Science. 2015;349(6246):432-436.Google ScholarCrossrefSearch ADS PubMed 6.Gámez-Díaz L, August D, Stepensky P, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223-230.Google ScholarCrossrefSearch ADS PubMed 7.Serwas NK, Hoeger B, Ardy RC, et al. Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis [published correction appears in Nat Commun. 2019;10:4555]. Nat Commun. 2019;10(1):3106.Google ScholarCrossrefSearch ADS PubMed 8.Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349(20):1907-1915.Google ScholarCrossrefSearch ADS PubMed 9.Hadjadj J, Aladjidi N, Fernandes H, et al; Members of the French Reference Center for Pediatric Autoimmune Cytopenia (CEREVANCE). Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019; 134(1):9-21.Google ScholarCrossrefSearch ADS PubMed 10.Aladjidi N, Fernandes H, Leblanc T, et al. Evans syndrome in children: long-term outcome in a prospective French national observational cohort. Front Pediatr. 2015;3:79.Google ScholarCrossrefSearch ADS PubMed 11.Pincez T, Fernandes H, Leblanc T, et al. Long term follow-up of pediatric-onset Evans syndrome: broad immunopathological manifestations and high treatment burden [published online ahead of print 14 January 2021]. Haematologica. doi:10.3324/haematol.2020.271106.12.Aladjidi N, Leverger G, Leblanc T, et al; Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE). New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica. 2011;96(5):655-663.Google ScholarCrossrefSearch ADS PubMed 13.Schwab C, Gabrysch A, Olbrich P, et al. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. J Allergy Clin Immunol. 2018;142(6):1932-1946.Google ScholarCrossrefSearch ADS PubMed 14.Kiykim A, Ogulur I, Dursun E, et al. Abatacept as a long-term targeted therapy for LRBA deficiency. J Allergy Clin Immunol Pract. 2019; 7(8):2790-2800.Google ScholarCrossrefSearch ADS PubMed 15.Hara R, Umebayashi H, Takei S, et al. Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study. Pediatr Rheumatol Online J. 2019;17(1):17.Google ScholarCrossrefSearch ADS PubMed 16.Harigai M, Ishiguro N, Inokuma S, et al. Safety and effectiveness of abatacept in Japanese non-elderly and elderly patients with rheumatoid arthritis in an all-cases post-marketing surveillance. Mod Rheumatol. 2019;29(5):747-755.Google ScholarCrossrefSearch ADS PubMed 17.Genovese MC, Pacheco-Tena C, Covarrubias A, et al. Long-term safety and efficacy of subcutaneous abatacept in patients with rheumatoid arthritis: 5-year results from a phase IIIb trial. J Rheumatol. 2018; 45(8):1085-1092.Google ScholarCrossrefSearch ADS PubMed 18.Ozen G, Pedro S, Schumacher R, Simon TA, Michaud K. Safety of abatacept compared with other biologic and conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: data from an observational study. Arthritis Res Ther. 2019;21(1):141.Google ScholarCrossrefSearch ADS PubMed 19.Randell RL, Becker ML. Safety updates in novel therapeutics for pediatric rheumatic disease. Curr Opin Rheumatol. 2021;33(5):403-408.Google ScholarCrossrefSearch ADS PubMed 20.Slatter MA, Engelhardt KR, Burroughs LM, et al. Hematopoietic stem cell transplantation for CTLA4 deficiency. J Allergy Clin Immunol. 2016;138(2):615-619.Google ScholarCrossrefSearch ADS PubMed 21.Seidel MG, Böhm K, Dogu F, et al; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation. Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2018;141(2):770-775.Google ScholarCrossrefSearch ADS PubMed © 2022 by The American Society of Hematology2022 You do not currently have access to this content. Sign in via your Institution

Topics & Concepts