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

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• 作者：Romain Micol ; MD ; MPH ; PhD^a ; ^c ; ^d ; ^&lowast ; ; ^§ ; ; Samer Kayal ; MD ; PhD^b ; ^c ; ^&lowast ; ; ^&Dagger ; ; Nizar Mahlaoui ; MD ; MSc^a ; ^d ; Julien Beauté ; MD ; MSc^a ; Pauline Brosselin ; MD ; MPH^a ; Yasmine Dudoit ; BS^a ; Gaë ; lle Obenga ; MD^a ; Vincent Barlogis ; MD^a ; ^e ; Nathalie Aladjidi ; MD^a ; ^f ; Kamila Kebaili ; MD^a ; ^g ; Caroline Thomas ; MD^a ; ^h ; Fabienne Dulieu ; MD^a ; ⁱ ; Fabrice Monpoux ; MD^a ; ^j ; Raphaë ; le Nové ; -Josserand ; MD^a ; ^k ; Isabelle Pellier ; MD^a ; ^l ; Olivier Lambotte ; MD ; PhD^a ; ^m ; Alexandra Salmon ; MD^a ; ⁿ ; Agathe Masseau ; MD^a ; ^o ; Pierre Galanaud ; MD^a ; ^p ; Eric Oksenhendler ; MD^a ; ^q ; Marie-Dominique Tabone ; MD^a ; ^r ; Pierre Teira ; MD^a ; ^s ; Hé ; lè ; ne Coignard-Biehler ; MD^t ; Fanny Lanternier ; MD^t ; Olivier Join-Lambert ; MD ; PhD^b ; ^c ; Gaë ; l Mouillot ; PhD^u ; Ioannis Theodorou ; MD ; PhD^u ; Jean-Claude Lecron ; PhD^v ; Marie-Alexandra Alyanakian ; MD ; PhD^c ; ^w ; Capucine Picard ; MD ; PhD^a ; ^c ; ^d ; ^x ; ^y ; Sté ; phane Blanche ; MD^a ; ^c ; ^d ; Olivier Hermine ; MD ; PhD^a ; ^c ; ^z ; Felipe Suarez ; MD ; PhD^a ; ^c ; ^z ; Marianne Debré ; MD^a ; ^d ; Marc Lecuit ; MD ; PhD^a ; ^c ; ^t ; ^aa ; Olivier Lortholary ; MD ; PhD^a ; ^c ; ^t ; Anne Durandy ; MD ; PhD^d ; ^bb ; Alain Fischer ; MD ; PhD^a ; ^c ; ^d ; ^bb ; ^{alain.fischer@inserm.fr}
• 关键词：Haemophilus influenzae ; infections ; immunoglobulins ; IgM ; immunodeficiency
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：129
• 期：3
• 页码：770-777
• 全文大小：499 K

文摘

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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.