Coexistence of (Partial) Immune Defects and Risk of Recurrent Respiratory Infections

Abstract

Background: Respiratory infections are major causes of morbidity and mortality, but determinants of susceptibility are poorly defined. We studied whether and to what extent immunologic and genetic factors are associated with increased susceptibility to respiratory infections. Methods: We evaluated the prevalence of IgA, IgM, IgG, and IgG subclass deficiencies, impairment in the antibody response against pneumococcal polysaccharides, G2m(n) allotypes, Fc␥RIIa polymorphisms, partial C2 and partial C4 deficiency, promoter polymorphisms in MBL2, and lymphocyte subset deficiencies in a control population and in consecutive children with recurrent respiratory infections. Results: IgA and/or IgG subclass deficiency was found in 27 of 55 patients (49%) and 6 of 43 controls (14%) (P ‫؍‬ 0.0006). An impaired antibody response to polysaccharides was found in 7 patients (19%) and in 0 of 37 controls (P ‫؍‬ 0.002). The Gm(n)marker was absent in 25 of 55 patients (45%) and 6 of 42 controls (14%) (P ‫؍‬ 0.009). The MBL2 variants O/O, A/O, and A/A occurred in 9, 14, and 32 of the 55 patients, respectively, and in 1, 19, and 23 of the 43 controls, respectively (P ‫؍‬ 0.05). There was no increase in the prevalence of partial C4 deficiency, C2 deficiency, lymphocyte subset deficiency, or Fc␥RIIa polymorphism in the patients compared to the controls. A combination of at least 2 immune defects was found in 31 of 55 patients (56%) and in 4 of 42 controls (11.6%) (P <0.0001). Conclusion: Specific antipolysaccharide antibody deficiency, IgA and/or IgG subclass deficiency, Gm(n) allotype, and MBL2 genotype are susceptibility factors for recurrent respiratory infections, and coexistence of sev-

Recurrent Respiratory Infections in Children – Definition, Diagnostic Approach, Treatment and Prevention

“…The children with estimated diagnosis of RRI usually have no significant alteration of the immune system and its functions. Coexistence of two or more partial mild immune deteriorations in children with RRI, which was observed by several authors, confirms the secondary post-infective nature of these changes (Bossuyt et al, 2007). It is probable, that all the observed non-specific deteriorations of immunity are rather the consequence of repeated viral infections than the predisposing factor leading to RRI.…”

“…According to the literature, several alterations in immune system and its function have been observed among children suffering from RRI (Atkinson et al, 2004;Bossuyt et al, 2007;Day et al, 2004;de Martino & Ballotti, 2007;Don et al, 2007;Finocchi et al, 2002;Gomi et al, 2004;Ianni et al, 2001;Kvestad et al, 2006;Li Volti et al, 2003;Ottenhoff et al, 2002;Pryjma et al, 1999) defects in the production post-infectious specific antibodies. The children with estimated diagnosis of RRI usually have no significant alteration of the immune system and its functions.…”

Defective pneumococcal antibody response in patients with recurrent respiratory tract infections

“…These patients may also have defective response to protein antigens. [11][12][13] Patients with SAD have an impaired antibody production against polysaccharide antigens whereas they have Data is presented as percentages. SAD: specific antibody deficiency, CVID: common variable immunodeficiency, AT: ataxia-telangiectasia, URI: upper respiratory tract infection.…”

Review of immunological and virological aspects as contributory factors in Sudden Unexpected Death in Infancy (SUDI)

“…IgA and IgG2 subclass deficiencies often coexist with other immune defects, such as complement (C)2 and C4 deficiencies, and are associated with recurrent susceptibility to infections [52]. These factors can therefore also contribute to the triple-risk model as part of the underlying vulnerabilities.…”