French national reference center for primary immunodeficiencies (CEREDIH)

Primary Immunodeficiencies (PID) may affect both children and adults. These are genetic diseases of the immune system that predispose to infections linked to a wide variety of infectious agents (common or opportunistic) that can reach different organs (e.g., the ENT sphere, the digestive tract, the lungs), but also to autoimmune diseases (linked to hyperactivity of the immune system), allergies, lymphoproliferative syndromes (increase in the size of the liver, spleen and lymph nodes) and possibly cancer.

Logo marihThis reference center is affiliated to the MARIH rare disease healthcare network and to Logo ERN RITAthe RITA European Reference Network (ERN).

Keywords: Primary immunodeficiencies; children; adults; infections; autoimmunity; inflammation; allergies; cancers; immunoglobulins; plasma-derived drugs; neonatal screening; Allogeneic hematopoietic stem cell transplantation; gene therapy; genomic medicine; personalized medicine; biostatistics; artificial intelligence.


Despina Moshous

Pr Despina Moshous

Dr Nizar Mahlaoui

Contact us

Talk to someone or make an appointment

Phone. + 33 1 44 49 48 24

> Secretary email address

> Outpatient email address

To write to CEREDIH from France (metropolitan France and French overseas departments and territories), send your mail, postage free, to :
75742 PARIS CEDEX 15

In case of emergency

The center’s missions are to :

  • Facilitate the diagnosis of primary immun0deficiencies (clinical, biological and genetic diagnosis, neonatal screening) and define a therapeutic management strategy within a specialized network of clinical physicians (pediatric and adult) and biologists; this network is coordinated by the CEREDIH and a national scientific committee.
  • Define and disseminate recommendations
  • Coordinate clinical, translational, epidemiological (national registry) and paramedical research.
  • Participate in training and information initiatives for healthcare professionals, patients and their families
  • Lead and coordinate health and medico-social networks and correspondents
  • Act as a privileged contact for guardians and patient associations
  • Train and inform the general public and all medical and paramedical healthcare professionals
  • Ensure smooth transition from pediatric to adult care
  • Liaise with the national IRIS and international IPOPI patient associations
  • Be active at European (ERN, learned societies) and international levels

> For further informations

  • Humoral immune deficiencies including agammaglobulinemia, common variable immune deficiency (CVID), hyper-IgM syndrome.
  • Cellular immune deficiencies including severe combined immune deficiencies (SCID or « boy in the bubble » syndrome), combined immune deficiencies, Wiskott Aldrich Syndrome
  • Deficits of innate immunity including chronic granulomatosis, leukocyte adhesion deficiency, immune deficiencies with elective microbial susceptibility.
  • Autoimmune and Immune dysregulation deficiencies, including autoimmune lymphoproliferative syndrome, hemophagocytic lymphohistyocytosis
  • Complement deficiencies
En savoir +

Timely and accurate diagnosis is key. Diagnotic delay leads to lower prognosis. Likelihood of being cured after a Hematopoietic Stem Cell Transplant (HSCT) for SCID is above 90% if performed in the first 3 months of life whereas it is only 70% if performed after 3 months old. Early onset of the best therapies dramatically increases the survival and the quality of life. Depending on the type and severity of each PID, treatment options may vary.

Below is a non exhautive list:

  • Long term prophylactic antiobiotics and/or antifungals
  • Immunoglobulins (antibodies derived from human plasma) infused intravenously (at home or hospital) or subcutaneously (at home)
  • Enzyme replacement therapy (for a rare form of SCID
  • Hematopoietic Stem Cell Transplant (HSCT) when necessary
  • Gene therapy (for a few PID as per now)

Prof. Despina Moshous, CEREDIH Chair, Pediatric Immuno-Hematology

Dr. Nizar Mahlaoui, CEREDIH Manager , Pediatric Immuno-Hematology

Prof. Olivier Lortholary, Head of the Adult Infectious and Tropical Diseases Unit

Prof. Capucine Picard, Head of the Study Center for Primary Immunodeficiencies – Laboratory of Immunology Analyses, Pediatric Immuno-Hematology

Prof. Felipe Suarez, Adult Hematology Unit

Prof. Olivier Hermine, Adult Hematology Unit

Prof. Stéphane Blanche, Head of the Pediatric Immuno-Hematology and Rheumatology Unit

Prof. Bénédicte Neven, Pediatric Immuno-Hematology

The drafters of the PNDS are subject to the obligation to produce a public declaration of interests.

Primary immunodeficiencies PNDS

Immunoglobulin replacement therapy infused at home (intravenously or subcutaneously) for children with humoral PID and their parents therapeutic education program

National Newborn Screening for Severe Combined Immunodeficiencies on the Guthrie card: health-economics research program (led by the Nantes University Hosp.) in collaboration with the health-economics research unit-Île-de-France, Hôtel-Dieu Hospital. 200,000 newborns were included in 50 maternities.

Quality of life study of children and adults patients with PID (national cohort, led by the Timone-Marseilles University Hosp.). More than 1,000 patients were included.

National Epidemiology of PID (national registry of PID run by CEREDIH) in collaboration with the Biostatistics laboratory of Necker-Imagine.

Design of a chip for the genetic diagnosis of PID (in collaboration with the Laboratory of Human Genetics, Imagine).

Inter-university diploma in pediatric immunohematology
(Aix-Marseille + Grenoble + Saint-Etienne + Nancy + Paris + Lyon + Lille universities).


A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency.
Chantal Lagresle-Peyrou, Aurélien Olichon, Hanem Sadek, Philippe Roche, Claudine Tardy, Cindy Da Silva, Alexandrine Garrigue, Alain Fischer, Despina Moshous, Yves Collette, Capucine Picard, Jean Laurent Casanova, Isabelle André, Marina Cavazzana
Haematologica, 2021 Feb 1, PMID: 31919089 PMCID: PMC7849581 DOI: 10.3324/haematol.2019.230250

Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories.
Jean-Laurent Casanova, Laurent Abel
Annu Rev Pathol, 2021 Jan 24, PMID: 32289233 PMCID: PMC7923385 DOI: 10.1146/annurev-pathol-031920-101429

Improving the diagnostic efficiency of primary immunodeficiencies with targeted next-generation sequencing.
Mathieu Fusaro, Jérémie Rosain, Virginie Grandin, Nathalie Lambert, Sylvain Hanein, Cécile Fourrage, Nicholas Renaud, Marine Gil, Samuel Chevalier, Wadih Abou Chahla, Brigitte Bader-Meunier
J Allergy Clin Immunol, 2021 Feb, PMID: 32531373 DOI: 10.1016/j.jaci.2020.05.046

DEF6 deficiency, a mendelian susceptibility to EBV infection, lymphoma, and autoimmunity.
Benjamin Fournier, Maud Tusseau, Marine Villard, Christophe Malcus, Emilie Chopin, Emmanuel Martin, Debora Jorge Cordeiro, Nicole Fabien, Mathieu Fusaro, Alexandra Gauthier et al.
J Allergy Clin Immunol, 2021 Feb, PMID: 32562707 DOI: 10.1016/j.jaci.2020.05.052

Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients.
Marie-Louise Frémond, Alice Hadchouel, Laureline Berteloot, Isabelle Melki, Violaine Bresson, Laura Barnabei, Nadia Jeremiah, Alexandre Belot, Vincent Bondet, Olivier Brocq et al.
J Allergy Clin Immunol Pract, 2021 Feb, PMID: 33217613 DOI: 10.1016/j.jaip.2020.11.007

Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.
Paul Bastard, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Marwa Chbihi, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Yoann Seeleuthner, Adrian Gervais et al.
J Exp Med, 2021 Apr 5, PMID: 33544838 PMCID: PMC7871457 DOI: 10.1084/jem.20202486

Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome.
Guillaume Taieb, Elsa Kaphan, Claire Duflos, Christine Lebrun-Frénay, Valérie Rigau, Eric Thouvenot, Emeline Duhin-Gand, Romain Lefaucheur, Khe Hoang-Xuan, Sarah Coulette, Jean Christophe Ouallet, Nicolas Menjot de Champfleur, Christine Tranchant, Capucine Picard, Mathieu Fusaro, Fernando E Sepulveda, Pierre Labauge, Geneviève de Saint Basile
Neurol Neuroimmunol Neuroinflamm, 2021 Mar 3, PMID: 33658321 PMCID: PMC7963436 DOI: 10.1212/NXI.0000000000000970

TLR8 gain of function: a tall surprise.
Bertrand Boisson, Jean-Laurent Casanova
Blood, 2021 May 6, PMID: 33956066 DOI: 10.1182/blood.2020010463

Association of rare predicted loss-of-function variants of influenza-related type I IFN genes with critical COVID-19 pneumonia.
Qian Zhang, Aurélie Cobat, Paul Bastard, Luigi D Notarangelo, Helen C Su, Laurent Abel, Jean-Laurent Casanova, COVID Human Genetic Effort (CHGE)
J Clin Invest, 2021 Aug 2, PMID: 34166232 PMCID: PMC8321559 DOI: 10.1172/JCI152474

Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child.
Masato Ogishi, Rui Yang, Caner Aytekin, David Langlais, Mathieu Bourgey, Taushif Khan, Fatima Al Ali, Mahbuba Rahman, Ottavia M Delmonte, Maya Chrabieh, Peng Zhang et al.
Nat Med, 2021 Sep, PMID: 34183838 PMCID: PMC8446316 DOI: 10.1038/s41591-021-01388-5

Mechanisms of viral inflammation and disease in humans.
Jean-Laurent Casanova, Laurent Abel
Science, 2021 Nov 26, PMID: 34822298 PMCID: PMC8697421 DOI: 10.1126/science.abj7965

Comment on \ »Aberrant type 1 immunity drives susceptibility to mucosal fungal infections\ ».
Anne Puel, Jean-Laurent Casanova
Science, 2021 Sep 17, PMID: 34529464 PMCID: PMC8509635 DOI: 10.1126/science.abi5459


Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage.
Marie-Louise Frémond, Marie Legendre, Michael Fayon, Annick Clement, Emilie Filhol-Blin, Nicolas Richard, Laura Berdah, Sylvie Roullaud, Gillian I Rice, Vincent Bondet, Darragh Duffy, Chiara Sileo, Hubert Ducou le Pointe, Hugues Beguere, Aurore Coulomb, Bénédicte Neven, Serge Amselem, Yanick Crow, Nadia Nathan
Thorax, 2020 Jan, PMID: 31666386 DOI: 10.1136/thoraxjnl-2019-213892

Gene therapy for severe combined immunodeficiencies and beyond.
Alain Fischer, Salima Hacein-Bey-Abina
J Exp Med, 2020 Jan 6, PMID: 31826240 PMCID: PMC7041706 DOI: 10.1084/jem.20190607

Mini review: Prevention of mother-child transmission of HIV: 25 years of continuous progress toward the eradication of pediatric AIDS?
Stéphane Blanche
Virulence, 2020 Dec, PMID: 31885324 PMCID: PMC6961731 DOI: 10.1080/21505594.2019.1697136

A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection.
Jean-Laurent Casanova, Helen C Su, COVID Human Genetic Effort
Cell, 2020 Jun 11, PMID: 32405102 PMCID: PMC7218368 DOI: 10.1016/j.cell.2020.05.016

Immigration in science.
Jean-Laurent Casanova, David M Holtzman, Susan M Kaech, Lewis L Lanier, Carl F Nathan, Alexander Y Rudensky, David Tuveson, Jedd D Wolchok
J Exp Med, 2020 Nov 2, PMID: 33057576 PMCID: PMC7563685 DOI: 10.1084/jem.20202055

JAK Inhibition in the Aicardi-Goutières Syndrome.
Bénédicte Neven, Buthaina Al Adba, Marie Hully, Isabelle Desguerre, Claire Pressiat, Natalie Boddaert, Darragh Duffy, Gillian I Rice, Luis Seabra, Marie-Louise Frémond, Stéphane Blanche, Yanick J Crow
N Engl J Med, 2020 Nov 26, PMID: 33252884 DOI: 10.1056/NEJMc2031081

Devastating Gynecological Infections in Women with STAT3 Deficiency.
Alexis Redor, François Danion, Perrine Parize, Olivia Chandesris, Jonathan Dbjay, Amélie Duréault, Guillaume Le Guenno, Celine Cazorla, Delphine Vergnon-Miszczycha, Anne Sophie Bats, Christine Bodemer, Cyrille Hoarau, Caroline Charlier, Nizar Mahlaoui, Marc Lecuit, Fanny Lanternier, Olivier Lortholary
Clin Infect Dis, 2020 Oct 23, PMID: 31916572 DOI: 10.1093/cid/ciaa020

Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency.
Scott B. Drutman, M.D., Ph.D., Davood Mansouri, M.D., M.P.H., Seyed Alireza Mahdaviani, M.D., Anna-Lena Neehus, M.S., David Hum, M.S., Ruslana Bryk, Ph.D., Nicholas Hernandez, B.S., Serkan Belkaya, Ph.D., Franck Rapaport, Ph.D., Benedetta Bigio, M.S., Robert Fisch, B.A., Mahbuba Rahman, Ph.D., et al.
N Engl J Med, 2020 Jan 30, PMID: 31995689 PMCID: PMC7063989 DOI: 10.1056/NEJMoa1910640

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling.
Alice Lepelley, Maria José Martin-Niclós, Melvin Le Bihan, Joseph A Marsh, Carolina Uggenti, Gillian I Rice, Vincent Bondet, Darragh Duffy, Jonny Hertzog, Jan Rehwinkel, Serge Amselem, Siham Boulisfane-El Khalifi, Mary Brennan, Edwin Carter, Lucienne Chatenoud, Stéphanie Chhun, Aurore Coulomb l’Hermine, Marine Depp, Marie Legendre, Karen J Mackenzie, Jonathan Marey, Catherine McDougall, Kathryn J McKenzie, Thierry Jo Molina, Bénédicte Neven, Luis Seabra, Caroline Thumerelle, Marie Wislez, Nadia Nathan, Nicolas Manel, Yanick J Crow, Marie-Louise Frémond
J Exp Med, 2020 Nov 2, PMID: 32725128 PMCID: PMC7596811 DOI: 10.1084/jem.20200600

Human TET2 bridges cancer and immunity.
Qian Zhang, Jean-Laurent Casanova
Blood, 2020 Aug 27, PMID: 32853377 DOI: 10.1182/blood.2020006881

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Qian Zhang, Paul Bastard, Zhiyong Liu, Jérémie Le Pen, Marcela Moncada-Velez, Jie Chen, Masato Ogishi, Ira K D Sabli, Stephanie Hodeib, Cecilia Korol, Jérémie Rosain, Kaya Bilguvar, Junqiang Ye, Alexandre Bolze, Benedetta Bigio, Rui Yang, Andrés Augusto Arias, Qinhua Zhou, Yu Zhang, Fanny Onodi, Sarantis Korniotis, Léa Karpf, Quentin Philippot, Marwa Chbihi, Lucie Bonnet-Madin, Karim Dorgham, Nikaïa Smith, William M Schneider, Brandon S Razooky, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Leen Moens, Ji Eun Han, Lazaro Lorenzo, Lucy Bizien, Philip Meade, Anna-Lena Neehus, Aileen Camille Ugurbi, Aurélien Corneau, Gaspard Kerner, Peng Zhang, Franck Rapaport, Yoann Seeleuthner, Jeremy Manry, Cecile Masson 20, Yohann Schmitt, Agatha Schlüter, Tom Le Voyer, Taushif Khan, Juan Li, Jacques Fellay, Lucie Roussel, Mohammad Shahrooei, Mohammed F Alosaimi, Davood Mansouri, Haya Al-Saud, Fahd Al-Mulla, Feras Almourfi, Saleh Zaid Al-Muhsen, Fahad Alsohime , Saeed Al Turki, Rana Hasanato, Diederik van de Beek, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angio, Paolo Bonfanti, Luisa Imberti, Alessandra Sottini, Simone Paghera, Eugenia Quiros-Rolda, Camillo Rossi, Andrew J Ole, Miranda F Tompkins, Camille Alba, Isabelle Vandernoot, Jean-Christophe Goffard, Guillaume Smit, Isabelle Migeotte, Filomeen Haerynck, Pere Soler-Palacin, Andrea Martin-Nalda, Roger Colobran, Pierre-Emmanuel Morange, Sevgi Keles, Fatma Çölkesen, Tayfun Ozcelik, Kadriye Kart Yasar, Sevtap Senoglu, Şemsi Nur Karabela, Carlos Rodríguez-Gallego, Giuseppe Novelli, Sami Hraiech 60, Yacine Tandjaoui-Lambiotte 61 62, Xavier Duval, Cédric Laouénan, COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; NIAID-USUHS/TAGC COVID Immunity Group; Andrew L Snow, Clifton L Dalgard, Joshua D Milner, Donald C Vinh, Trine H Mogensen, Nico Marr, András N Spaan, Bertrand Boisson, Stéphanie Boisson-Dupuis 1 2 3, Jacinta Bustamant, Anne Puel, Michael J Ciancanelli, Isabelle Meyts, Tom Maniatis, Vassili Soumelis, Ali Amara, Michel Nussenzweig, Adolfo García-Sastre, Florian Krammer, Aurora Pujol, Darragh Duffy, Richard P Lifton, Shen-Ying Zhang, Guy Gorochov, Vivien Béziat, Emmanuelle Jouanguy, Vanessa Sancho-Shimizu, Charles M Rice, Laurent Abel, Luigi D Notarangelo, Aurélie Cobat, Helen C Su, Jean-Laurent Casanova
Science, 2020 Oct 23, PMID: 32972995 PMCID: PMC7857407 DOI: 10.1126/science.abd4570

Autoantibodies against type I IFNs in patients with life-threatening COVID-19.
Paul Bastard, Lindsey b. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Yu Zhang, Karim Dorgham, Quentin Philippot, Jérémie Rosain[…]Jean-laurent Casanova
Science, 2020 Oct 23, PMID: 32972996 PMCID: PMC7857397 DOI: 10.1126/science.abd4585

Safety and efficacy of brentuximab vedotin as a treatment for lymphoproliferative disorders in primary immunodeficiencies.
Thomas Pincez, Julie Bruneau, Laureline Berteloot, Eve Piekarski, Caroline Thomas, Ambroise Marçais, Amélie Trinquand, Martin Castelle, Nicolas Garcelon, Dominique Plantaz, Morgane Cheminant, Despina Moshous, Thierry Jo Molina, Olivier Hermine, Elizabeth Macintyre , Alain Fischer, Stéphane Blanche, Felipe Suarez, Bénédicte Neven
Haematologica, 2020 Sep 1, PMID: 33054064 PMCID: PMC7556515 DOI: 10.3324/haematol.2019.230276

Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria.
Rui Yang, Federico Mele, Lisa Worley, David Langlais, Jérémie Rosain, Ibithal Benhsaien, Houda Elarabi, Carys A Croft, Jean-Marc Doisn, Peng Zhang , Marc Weisshaar, David Jarrossay, Daniela Latorre, Yichao Shen, Jing Han, Masato Ogishi, Conor Gruber, Janet Markle, Fatima Al Ali, Mahbuba Rahman, Taushif Khan, Yoann Seeleuthner, Gaspard Kerner, Lucas T Husquin, Julia L Maclsaac, Mohamed Jeljeli, Abderrahmane Errami, Fatima Ailal, Michael S Kobor, Carmen Oleaga-Quintas, Manon Roynard, Mathieu Bourgey, Jamila El Baghdadi, Stéphanie Boisson-Dupuis, Anne Puel, Fréderic Batteux, Flore Rozenberg, Nico Marr, Qiang Pan-Hammarström, Dusan Bogunovic, Lluis Quintana-Murci, Thomas Carroll, Cindy S Ma, Laurent Abel, Aziz Bousfiha, James P Di Santo, Laurie H Glimcher, Philippe Gros, Stuart G Tangye, Federica Sallusto, Jacinta Bustamante, Jean-Laurent Casanova
Cell, 2020 Dec 23, PMID: 33296702 PMCID: PMC7770098 (available on 2021-12-23) DOI: 10.1016/j.cell.2020.10.046


Burden of Poor Health Conditions and Quality of Life in 656 Children with Primary Immunodeficiency.
Barlogis V, Mahlaoui N, Auquier P, Fouyssac F, Pellier I, Vercasson C,        Allouche M, De Azevedo CB, Moshous D, Neven B, Pasquet M, Jeziorski E, Aladjidi N, Thomas C, Gandemer V, Mazingue F, Picard C, Blanche S, Michel G, Fischer A.
J Pediatr. 2017 Nov 30. pii: S0022-3476(17)31378-1. doi: 10.1016/j.jpeds.2017.10.029. [Epub ahead of print] PubMed PMID: 29198545.

Prevalence of primary immunodeficiencies in France is underestimated.
Mahlaoui N, Jais JP, Brosselin P, Mignot C, Beaurain B, Brito C, Costes L, Courteille V, De Vergnes N, Alcaïs A, Fischer A; CEREDIH Prevalence Study Collaborators.
J Allergy Clin Immunol. 2017 Dec;140(6):1731-1733. doi: 10.1016/j.jaci.2017.06.020. Epub 2017 Jul 18. PubMed PMID: 28732644.

Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies.
Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N; members of the CEREDIH French PID study group.
J Allergy Clin Immunol. 2017 Nov;140(5):1388-1393.e8. doi: 10.1016/j.jaci.2016.12.978. Epub 2017 Feb 10. PubMed PMID: 28192146.


Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.
Micol R, Kayal S, Mahlaoui N, Beauté J, Brosselin P, Dudoit Y, Obenga G, Barlogis V, Aladjidi N, Kebaili K, Thomas C, Dulieu F, Monpoux F, Nové-Josserand  R, Pellier I, Lambotte O, Salmon A, Masseau A, Galanaud P, Oksenhendler E, Tabone MD, Teira P, Coignard-Biehler H, Lanternier F, Join-Lambert O, Mouillot G, Theodorou I, Lecron JC, Alyanakian MA, Picard C, Blanche S, Hermine O, Suarez F, Debré M, Lecuit M, Lortholary O, Durandy A, Fischer A.
J Allergy Clin Immunol. 2012 Mar;129(3):770-7. doi: 10.1016/j.jaci.2011.09.047. Epub 2011 Dec 6. PubMed PMID: 22153772.


The French national registry of primary immunodeficiency diseases.
CEREDIH: The French PID study group.
Clin Immunol. 2010 May;135(2):264-72. doi: 10.1016/j.clim.2010.02.021. PubMed PMID: 20399414.

Contact information

Necker-Enfants malades university hospital
> Pediatric immuno-hematology and rheumatology department

149 rue de Sèvres
75743 PARIS Cedex 15

In Necker, the CEREDIH in brief 

patients followed at least once a year*
medical consultations*
day hospitalizations*
fully hospitalized patients*
authorized therapeutic education program*
patients trained in therapeutic education*
current research projects*
university courses*
teleconsultation procedures*

* data valid for 2022