Equipe médicale :

Recherche :

La recherche du centre est organisée en plusieurs volets :

Recherche clinique en implémentant la cohorte nationale DEFI, qui recrute des patients ayant un déficit immunitaire en immunoglobulines. Cette cohorte a permis d’améliorer les connaissances sur ce déficit immunitaire particulier et a donné lieux à de nombreuses publications, nationales ou en collaboration avec des équipes européennes.

A la frontière de la recherche clinique et de la recherche fondamentale : le Plan France Médecine Génomique 2025 : les déficits immunitaires ont été reconnus en 2020 comme pré-indication prioritaire du PFMG2025. Ce plan vise à faire le diagnostic génétique de patients qui ont un déficit immunitaire, en analysant de façon comparative leur génome et celui de leurs apparentés. Les études sont réalisées sur la plateforme génomique du site Broussais, à Paris.

Recherche fondamentale, en lien avec l’équipe du Pr Guy Gorochov à la Pitié-Salpêtrière à Paris (INSERM U1135), pour les dysfonctions du système immunitaire qui conduisent à l’atteinte digestive et hépatique des déficits en anticorps (Dr Jehane Fadlallah, Dr Marion Malphettes)

Recherche fondamentale pour les diagnostics moléculaires non établis, en lien avec l’institut IMAGINE à Paris (Pr Jean-Laurent Casanova, Dr Frédéric Rieux-Laucat, Dr Jean-Pierre de Villartay, Dr Sylvain Latour, INSERM U1163)

Publications : 

Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppänen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I. The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee. J Clin Immunol. 2021 Feb 18:1–14. doi: 10.1007/s10875-021-00980-1. Epub ahead of print. PMID: 33598806; PMCID: PMC7889474.

Delplanque M, Galicier L, Oziol E, Ducharme-Bénard S, Oksenhendler E, Buob D, Grateau G, Boutboul D, Georgin-Lavialle S. AA Amyloidosis Secondary to Primary Immune Deficiency: About 40 Cases Including 2 New French Cases and a Systematic Literature Review. J Allergy Clin Immunol Pract. 2021 Feb;9(2):745-752.e1. doi: 10.1016/j.jaip.2020.09.023. Epub 2020 Sep 30. PMID: 33007500.

Coignard-Biehler H, Mahlaoui N, Pilmis B, Barlogis V, Brosselin P, De Vergnes N, Debré M, Malphettes M, Frange P, Catherinot E, Pellier I, Durieu I, Perlat A, Royer B, Quellec AL, Jeziorski E, Fischer A, Lortholary O; CEREDIH French PID study group. Correction to: A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency. J Clin Immunol. 2020 Jul;40(5):786-787. doi: 10.1007/s10875-020-00793-8. Erratum for: J Clin Immunol. 2019 Oct;39(7):702-712. PMID: 32578002.

Fusaro M, Rosain J, Grandin V, Lambert N, Hanein S, Fourrage C, Renaud N, Gil M, Chevalier S, Chahla WA, Bader-Meunier B, Barlogis V, Blanche S, Boutboul D, Castelle M, Comont T, Diana JS, Fieschi C, Galicier L, Hermine O, Lefèvre-Utile A, Malphettes M, Merlin E, Oksenhendler E, Pasquet M, Suarez F, André I, Béziat V, De Saint Basile G, De Villartay JP, Kracker S, Lagresle-Peyrou C, Latour S, Rieux-Laucat F, Mahlaoui N, Bole C, Nitschke P, Hulier-Ammar E, Fischer A, Moshous D, Neven B, Alcais A, Vogt G, Bustamante J, Picard C. Improving the diagnostic efficiency of primary immunodeficiencies with targeted next-generation sequencing. J Allergy Clin Immunol. 2021 Feb;147(2):734-737. doi: 10.1016/j.jaci.2020.05.046. Epub 2020 Jun 10. PMID: 32531373.

Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F; Primary Immunodeficiency Consortium for the NIHR Bioresource, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, Smith KGC. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature. 2020 Jul;583(7814):90-95. doi: 10.1038/s41586-020-2265-1. Epub 2020 May 6. Erratum in: Nature. 2020 Aug;584(7819):E2. PMID: 32499645; PMCID: PMC7334047.

Lorenzini T, Fliegauf M, Klammer N, Frede N, Proietti M, Bulashevska A, Camacho-Ordonez N, Varjosalo M, Kinnunen M, de Vries E, van der Meer JWM, Ameratunga R, Roifman CM, Schejter YD, Kobbe R, Hautala T, Atschekzei F, Schmidt RE, Schröder C, Stepensky P, Shadur B, Pedroza LA, van der Flier M, Martínez-Gallo M, Gonzalez-Granado LI, Allende LM, Shcherbina A, Kuzmenko N, Zakharova V, Neves JF, Svec P, Fischer U, Ip W, Bartsch O, Barış S, Klein C, Geha R, Chou J, Alosaimi M, Weintraub L, Boztug K, Hirschmugl T, Dos Santos Vilela MM, Holzinger D, Seidl M, Lougaris V, Plebani A, Alsina L, Piquer-Gibert M, Deyà-Martínez A, Slade CA, Aghamohammadi A, Abolhassani H, Hammarström L, Kuismin O, Helminen M, Allen HL, Thaventhiran JE, Freeman AF, Cook M, Bakhtiar S, Christiansen M, Cunningham-Rundles C, Patel NC, Rae W, Niehues T, Brauer N, Syrjänen J, Seppänen MRJ, Burns SO, Tuijnenburg P, Kuijpers TW; NIHR BioResource, Warnatz K, Grimbacher B; NIHR BioResource. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations. J Allergy Clin Immunol. 2020 Oct;146(4):901-911. doi: 10.1016/j.jaci.2019.11.051. Epub 2020 Apr 9. PMID: 32278790.

Oksenhendler E, Spaan AN, Neven B, Stolzenberg MC, Fusaro M, Casanova JL, Rieux-Laucat F, Boisson B, Magérus A. Autoimmune Lymphoproliferative Syndrome Presenting with Invasive Streptococcus pneumoniae Infection. J Clin Immunol. 2020 Apr;40(3):543-546. doi: 10.1007/s10875-020-00765-y. Epub 2020 Mar 6. PMID: 32144537.

Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Torgerson TR, Casanova JL, Sullivan KE, Tangye SG. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020 Jan;40(1):66-81. doi: 10.1007/s10875-020-00758-x. Epub 2020 Feb 11. PMID: 32048120; PMCID: PMC7082388.

Coignard-Biehler H, Mahlaoui N, Pilmis B, Barlogis V, Brosselin P, De Vergnes N, Debré M, Malphettes M, Frange P, Catherinot E, Pellier I, Durieu I, Perlat A, Royer B, Le Quellec A, Jeziorski E, Fischer A, Lortholary O; CEREDIH French PID study group, Aaron L, Adoue D, Aguilar C, Aladjidi N, Alcais A, Amoura Z, Arlet P, Armari-Alla C, Bader-Meunier B, Bayart S, Bertrand Y, Bienvenu B, Blanche S, Bodet D, Bonnotte B, Borie R, Boutard P, Briandet C, Brion JP, Brouard J, Cohen-Beaussant S, Costes L, Couderc LJ, Cougoul P, Courteille V, de Saint Basile G, Devoldere C, Deville A, Donadieu J, Dore E, Dulieu F, Edan C, Entz-Werle N, Fieschi C, Forestier A, Fouyssac F, Gajdos V, Galicier L, Gandemer V, Gardembas M, Gaud C, Guillerm G, Hachulla E, Hamidou M, Hermine O, Hoarau C, Humbert S, Jaccard A, Jacquot S, Jais JP, Jaussaud R, Jeandel PY, Kebaili K, Korganow AS, Lambotte O, Lanternier F, Larroche C, Lascaux AS, Le Moigne E, Le Moing V, Lebranchu Y, Lecuit M, Lefevre G, Lemal R, Te VLT, Marie-Cardine A, Silva NM, Masseau A, Massot C, Mazingue F, Merlin E, Michel G, Millot F, Monlibert B, Monpoux F, Moshous D, Mouthon L, Munzer M, Neven B, Nove-Josserand R, Oksenhendler E, Ouachée-Chardin M, Oudot C, Pagnier A, Pasquali JL, Pasquet M, Perel Y, Picard C, Piguet C, Plantaz D, Provot J, Quartier P, Rieux-Laucat F, Roblot P, Roger PM, Rohrlich PS, Rubie H, Salle V, Sarrot-Reynauld F, Servettaz A, Stephan JL, Schleinitz N, Suarez F, Swiader L, Taque S, Thomas C, Tournilhac O, Thumerelle C, Tron F, Vannier JP, Viallard JF. A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency. J Clin Immunol. 2019 Oct;39(7):702-712. doi: 10.1007/s10875-019-00658-9. Epub 2019 Aug 10. Erratum in: J Clin Immunol. 2020 Jul;40(5):786-787. PMID: 31401750.

Bouafia A, Lofek S, Bruneau J, Chentout L, Lamrini H, Trinquand A, Deau MC, Heurtier L, Meignin V, Picard C, Macintyre E, Alibeu O, Bras M, Molina TJ, Cavazzana M, André-Schmutz I, Durandy A, Fischer A, Oksenhendler E, Kracker S. Loss of ARHGEF1 causes a human primary antibody deficiency. J Clin Invest. 2019 Mar 1;129(3):1047-1060. doi: 10.1172/JCI120572. Epub 2019 Feb 4. PMID: 30521495; PMCID: PMC6391114.

Mahlaoui N, Picard C, Bach P, Costes L, Courteille V, Ranohavimparany A, Alcaïs A, Jais JP, Fischer A; CEREDIH French PID study group. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry. J Allergy Clin Immunol. 2019 Apr;143(4):1646-1649.e10. doi: 10.1016/j.jaci.2018.12.994. Epub 2019 Jan 9. PMID: 30639347.

Fadlallah J, Sterlin D, Fieschi C, Parizot C, Dorgham K, El Kafsi H, Autaa G, Ghillani-Dalbin P, Juste C, Lepage P, Malphettes M, Galicier L, Boutboul D, Clément K, André S, Marquet F, Tresallet C, Mathian A, Miyara M, Oksenhendler E, Amoura Z, Yssel H, Larsen M, Gorochov G. Synergistic convergence of microbiota- specific systemic IgG and secretory IgA. J Allergy Clin Immunol. 2019 Apr;143(4):1575-1585.e4. doi: 10.1016/j.jaci.2018.09.036. Epub 2018 Dec 13. PMID: 30554723.

Dion J, Malphettes M, Bénéjat L, Mégraud F, Wargnier A, Boutboul D, Galicier L, Le Moing V, Giraud P, Jaccard A, Nove-Josserand R, Fieschi C, Oksenhendler E, Gérard L; DEFI study group. Campylobacter infection in adult patients with primary antibody deficiency. J Allergy Clin Immunol Pract. 2019 Mar;7(3):1038-1041.e4. doi: 10.1016/j.jaip.2018.06.014. Epub 2018 Jul 6. PMID: 29981862.

Mahévas T, Bertinchamp R, Battistella M, Reygagne P, Oksenhendler E, Fieschi C, Bachelez H. Efficacy of oral sirolimus as salvage therapy in refractory lichen planus associated with immune deficiency. Br J Dermatol. 2018 Sep;179(3):771-773. doi: 10.1111/bjd.16555. Epub 2018 Jun 26. PMID: 29573394.

Berland A, Rosain J, Kaltenbach S, Allain V, Mahlaoui N, Melki I, Fievet A, Dubois d’Enghien C, Ouachée-Chardin M, Perrin L, Auger N, Cipe FE, Finocchi A, Dogu F, Suarez F, Moshous D, Leblanc T, Belot A, Fieschi C, Boutboul D, Malphettes M, Galicier L, Oksenhendler E, Blanche S, Fischer A, Revy P, Stoppa-Lyonnet D, Picard C, de Villartay JP. PROMIDISα: A T-cell receptor α signature associated with immunodeficiencies caused by V(D)J recombination defects. J Allergy Clin Immunol. 2019 Jan;143(1):325-334.e2. doi: 10.1016/j.jaci.2018.05.028. Epub 2018 Jun 12. PMID: 29906526.

Fadlallah J, El Kafsi H, Sterlin D, Juste C, Parizot C, Dorgham K, Autaa G, Gouas D, Almeida M, Lepage P, Pons N, Le Chatelier E, Levenez F, Kennedy S, Galleron N, de Barros JP, Malphettes M, Galicier L, Boutboul D, Mathian A, Miyara M, Oksenhendler E, Amoura Z, Doré J, Fieschi C, Ehrlich SD, Larsen M, Gorochov G. Microbial ecology perturbation in human IgA deficiency. Sci Transl Med. 2018 May 2;10(439):eaan1217. doi: 10.1126/scitranslmed.aan1217. PMID: 29720448.

Vince N, Mouillot G, Malphettes M, Limou S, Boutboul D, Guignet A, Bertrand  V, Pellet P, Gourraud PA, Debré P, Oksenhendler E, Théodorou I, Fieschi C; DEFI Study Group. Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management. Hum Immunol. 2018 Jul;79(7):571-577. doi: 10.1016/j.humimm.2018.04.014. Epub 2018 Apr 27. PMID: 29709555.

Oleaga-Quintas C, de Oliveira-Júnior EB, Rosain J, Rapaport F, Deswarte C, Guérin A, Sajjath SM, Zhou YJ, Marot S, Lozano C, Branco L, Fernández-Hidalgo N, Lew DB, Brunel AS, Thomas C, Launay E, Arias AA, Cuffel A, Monjo VC, Neehus AL, Marques L, Roynard M, Moncada-Vélez M, Gerçeker B, Colobran R, Vigué MG, Lopez-Herrera G, Berron-Ruiz L, Méndez NHS, O’Farrill Romanillos P, Le Voyer T, Puel A, Bellanné-Chantelot C, Ramirez KA, Lorenzo-Diaz L, Alejo NR, de Diego RP, Condino-Neto A, Mellouli F, Rodriguez-Gallego C, Witte T, Restrepo JF, Jobim M, Boisson-Dupuis S, Jeziorski E, Fieschi C, Vogt G, Donadieu J, Pasquet M, Vasconcelos J, Ardeniz FO, Martínez-Gallo M, Campos RA, Jobim LF, Martínez-Barricarte R, Liu K, Cobat A, Abel L, Casanova JL, Bustamante J. Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance. J Clin Immunol. 2021 Jan 8. doi: 10.1007/s10875-020-00930-3. Epub ahead of print. PMID: 33417088.

Meyts I, Bucciol G, Quinti I, Neven B, Fischer A, Seoane E, Lopez-Granados E, Gianelli C, Robles-Marhuenda A, Jeandel PY, Paillard C, Sankaran VG, Demirdag YY, Lougaris V, Aiuti A, Plebani A, Milito C, Dalm VA, Guevara-Hoyer K, Sánchez- Ramón S, Bezrodnik L, Barzaghi F, Gonzalez-Granado LI, Hayman GR, Uzel G, Mendonça LO, Agostini C, Spadaro G, Badolato R, Soresina A, Vermeulen F, Bosteels C, Lambrecht BN, Keller M, Mustillo PJ, Abraham RS, Gupta S, Ozen A, Karakoc-Aydiner E, Baris S, Freeman AF, Yamazaki-Nakashimada M, Scheffler- Mendoza S, Espinosa-Padilla S, Gennery AR, Jolles S, Espinosa Y, Poli MC, Fieschi C, Hauck F, Cunningham-Rundles C, Mahlaoui N; IUIS Committee of Inborn Errors of Immunity, Warnatz K, Sullivan KE, Tangye SG. Coronavirus disease 2019 in patients with inborn errors of immunity: An international study. J Allergy Clin Immunol. 2021 Feb;147(2):520-531. doi: 10.1016/j.jaci.2020.09.010. Epub 2020 Sep 24. PMID: 32980424; PMCID: PMC7832563.

Pérot P, Bielle F, Bigot T, Foulongne V, Bolloré K, Chrétien D, Gil P, Gutiérrez S, L’Ambert G, Mokhtari K, Hellert J, Flamand M, Tamietti C, Coulpier M, Huard de Verneuil A, Temmam S, Couderc T, De Sousa Cunha E, Boluda S, Plu I, Delisle MB, Bonneville F, Brassat D, Fieschi C, Malphettes M, Duyckaerts C, Mathon B, Demeret S, Seilhean D, Eloit M. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia. Clin Infect Dis. 2020 Jun 9:ciaa308. doi: 10.1093/cid/ciaa308. Epub ahead of print. PMID: 32516409.

Béziat V, Tavernier SJ, Chen YH, Ma CS, Materna M, Laurence A, Staal J, Aschenbrenner D, Roels L, Worley L, Claes K, Gartner L, Kohn LA, De Bruyne M, Schmitz-Abe K, Charbonnier LM, Keles S, Nammour J, Vladikine N, Maglorius Renkilaraj MRL, Seeleuthner Y, Migaud M, Rosain J, Jeljeli M, Boisson B, Van Braeckel E, Rosenfeld JA, Dai H, Burrage LC, Murdock DR, Lambrecht BN, Avettand- Fenoel V, Vogel TP; Undiagnosed Diseases Network, Esther CR, Haskologlu S, Dogu F, Ciznar P, Boutboul D, Ouachée-Chardin M, Amourette J, Lebras MN, Gauvain C, Tcherakian C, Ikinciogullari A, Beyaert R, Abel L, Milner JD, Grimbacher B, Couderc LJ, Butte MJ, Freeman AF, Catherinot É, Fieschi C, Chatila TA, Tangye SG, Uhlig HH, Haerynck F, Casanova JL, Puel A. Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome. J Exp Med. 2020 Jun 1;217(6):e20191804. doi: 10.1084/jem.20191804. Erratum in: J Exp Med. 2020 Jun 1;217(7): PMID: 32207811.

Sterlin D, Fadlallah J, Adams O, Fieschi C, Parizot C, Dorgham K, Rajkumar A, Autaa G, El-Kafsi H, Charuel JL, Juste C, Jönsson F, Candela T, Wardemann H, Aubry A, Capito C, Brisson H, Tresallet C, Cummings RD, Larsen M, Yssel H, von Gunten S, Gorochov G. Human IgA binds a diverse array of commensal bacteria. J Exp Med. 2020 Mar 2;217(3):e20181635. doi: 10.1084/jem.20181635. Erratum in: J Exp Med. 2020 Mar 2;217(3): PMID: 31891367; PMCID: PMC7062531.

El Sissy C, Rosain J, Vieira-Martins P, Bordereau P, Gruber A, Devriese M, de Pontual L, Taha MK, Fieschi C, Picard C, Frémeaux-Bacchi V. Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies. Front Immunol. 2019 Aug 8;10:1936. doi: 10.3389/fimmu.2019.01936. PMID: 31440263; PMCID: PMC6694794.

Sterlin D, Fieschi C, Malphettes M, Larsen M, Gorochov G, Fadlallah J. Immune/microbial interface perturbation in human IgA deficiency. Gut Microbes. 2019;10(3):429-433. doi: 10.1080/19490976.2018.1546520. Epub 2018 Nov 18. PMID: 30449244; PMCID: PMC6546332.

Donadieu J, Lamant M, Fieschi C, de Fontbrune FS, Caye A, Ouachee M, Beaupain B, Bustamante J, Poirel HA, Isidor B, Van Den Neste E, Neel A, Nimubona S, Toutain F, Barlogis V, Schleinitz N, Leblanc T, Rohrlich P, Suarez F, Ranta D, Chahla WA, Bruno B, Terriou L, Francois S, Lioure B, Ahle G, Bachelerie F, Preudhomme C, Delabesse E, Cave H, Bellanné-Chantelot C, Pasquet M; French GATA2 study group. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. Haematologica. 2018 Aug;103(8):1278-1287. doi: 10.3324/haematol.2017.181909. Epub 2018 May 3. PMID: 29724903; PMCID: PMC6068047.

Lopez B, Bahuaud M, Fieschi C, Mehlal S, Jeljeli M, Rogeau S, Brabant S, Deleplancque AS, Dubucquoi S, Poizot S, Terriou L, Launay D, Batteux F, Labalette M, Lefèvre G. Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies. Front Immunol. 2017 Dec 20;8:1862. doi: 10.3389/fimmu.2017.01862. PMID: 29326723; PMCID: PMC5742330.

Réseau national des centres de référence des déficits immunitaires héréditaires (CEREDIH) :

Le centre de l’hôpital Saint-Louis est constitutif du centre de référence des déficits immunitaires héréditaires (CEREDIH). Le CEREDIH est constitué d’un centre coordonnateur (Hôpital Necker-Enfants malades, Paris), et de 5 centres constitutifs (Saint-Louis, Marseille, Angers, Lille , Nantes) et de 27 centres de compétence répartis sur le territoire national.