Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.

Romain Micol , Samer Kayal (1) , Nizar Mahlaoui (2, 3) , Julien Beauté (4) , Pauline Brosselin , Yasmine Dudoit , Gaëlle Obenga , Vincent Barlogis (5) , Nathalie Aladjidi (6) , Kamila Kebaili (7) , Caroline Thomas (8) , Fabienne Dulieu , Fabrice Monpoux , Raphaële Nové-Josserand (9) , Isabelle Pellier (10) , Olivier Lambotte (11) , Alexandra Salmon (12) , Agathe Masseau (13) , Pierre Galanaud (14) , Eric Oksenhendler (15) , Marie-Dominique Tabone , Pierre Teira , Hélène Coignard-Biehler , Fanny Lanternier (16) , Olivier Join-Lambert (17) , Gaël Mouillot (18) , Ioannis Theodorou (19) , Jean-Claude Lecron (20) , Marie-Alexandra Alyanakian (2) , Capucine Picard (21, 1, 22) , Stéphane Blanche (2) , Olivier Hermine (23, 3) , Felipe Suarez (3, 23) , Marianne Debré (2) , Marc Lecuit (16, 24) , Olivier Lortholary (3, 16) , Anne Durandy (3, 25) , Alain Fischer (21, 26, 27)

1 Hôpital Necker - Enfants Malades [AP-HP]
2 Service d'immuno-hématologie pédiatrique [CHU Necker]
3 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
4 Institut Pasteur du Cambodge
5 Service d'hématologie pédiatrique
6 Service d'Hémato-oncologie Pédiatrique
7 Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse
8 Hématologie et oncologie pédiatrique
9 Service de Médecine Interne - Centre Hospitalier Lyon Sud
10 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
11 service de médecine interne
12 Service de Génétique [CHRU Nancy]
13 Service de médecine interne
14 Cytokines, chimiokines et immunopathologie
15 Service d'immunologie clinique
16 Centre d'infectiologie Necker-Pasteur [CHU Necker]
17 UMR_S 570 - Pathogénie des infections systémiques
18 Immunité et Infection
19 Immunologie cellulaire et tissulaire
20 Modélisations pharmacocinétiques-pharmacodynamiques pour un meilleur usage des anti-infectieux
21 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
22 INSERM 980, Laboratory of Human Genetics of Infectious Disease
23 ERL 8254 - Equipe Inserm U1163 - Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications
24 Equipe avenir - Microorganismes et Barrières de l'Hôte
25 Developpement Normal et Pathologique du Système Immunitaire
26 Laboratoire du D eveloppement Normal et Pathologique du Syst eme Immunitaire
27 Unit e d'Immunologie et H ematologie P ediatrique

BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.

Mots clés: Haemophilus influenzae; infections; immunoglobulins; IgM; immunodeficiency

Domaines: Microbiologie et Parasitologie

Romain Micol, Samer Kayal, Nizar Mahlaoui, Julien Beauté, Pauline Brosselin, et al.. Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.. Journal of Allergy and Clinical Immunology, 2012, 129 (3), pp.770-7. ⟨10.1016/j.jaci.2011.09.047⟩. ⟨hal-00796444⟩