title: Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.
abstract: 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.
authors.affiliation: CEREDIH Network (French National Reference Center for Primary Immunodeficiencies), Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Micol
authors.forename: Samer
authors.initials: S
authors.lastname: Kayal
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Julien
authors.initials: J
authors.lastname: Beauté
authors.forename: Pauline
authors.initials: P
authors.lastname: Brosselin
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Dudoit
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Obenga
authors.forename: Vincent
authors.initials: V
authors.lastname: Barlogis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Aladjidi
authors.forename: Kamila
authors.initials: K
authors.lastname: Kebaili
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dulieu
authors.forename: Fabrice
authors.initials: F
authors.lastname: Monpoux
authors.forename: Raphaële
authors.initials: R
authors.lastname: Nové-Josserand
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellier
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Alexandra
authors.initials: A
authors.lastname: Salmon
authors.forename: Agathe
authors.initials: A
authors.lastname: Masseau
authors.forename: Pierre
authors.initials: P
authors.lastname: Galanaud
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Tabone
authors.forename: Pierre
authors.initials: P
authors.lastname: Teira
authors.forename: Hélène
authors.initials: H
authors.lastname: Coignard-Biehler
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.forename: Olivier
authors.initials: O
authors.lastname: Join-Lambert
authors.forename: Gaël
authors.initials: G
authors.lastname: Mouillot
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
authors.forename: Marie-Alexandra
authors.initials: MA
authors.lastname: Alyanakian
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D000361:Agammaglobulinemia / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism*; D002648:Child; D005260:Female; D006192:Haemophilus Infections / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D015994:Incidence; D008297:Male; D011446:Prospective Studies; D012137:Respiratory System / Q000276:immunology / Q000473:pathology / Q000821:virology; D012306:Risk
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M