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

J Allergy Clin Immunol. 2012 Mar;129(3):770-7. doi: 10.1016/j.jaci.2011.09.047. Epub 2011 Dec 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Agammaglobulinemia / complications
  • Agammaglobulinemia / epidemiology
  • Agammaglobulinemia / immunology*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / metabolism*
  • Child
  • Female
  • Haemophilus Infections / complications
  • Haemophilus Infections / epidemiology
  • Haemophilus Infections / immunology*
  • Haemophilus influenzae / immunology*
  • Haemophilus influenzae / pathogenicity
  • Humans
  • Hyper-IgM Immunodeficiency Syndrome / complications
  • Hyper-IgM Immunodeficiency Syndrome / epidemiology
  • Hyper-IgM Immunodeficiency Syndrome / immunology*
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism*
  • Incidence
  • Male
  • Prospective Studies
  • Respiratory System / immunology
  • Respiratory System / pathology
  • Respiratory System / virology
  • Risk


  • Antibodies, Viral
  • Immunoglobulin M