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Subtle Immunodeficiency in Severe Asthma: IgA and IgG2 Correlate with Lung Function and Symptoms

Background: Atopy, increased serum IgE and eosinophilic airway inflammation are common in asthma and may indicate aberrant immune responses, but the cause(s) are unknown. It was hypothesized that differences in serum immunoglobulins, immunoglobulin free light chains (FLC) and secretory IgA (sIgA) would exist between subjects with asthma of varying severity and normal subjects, and the levels would correlate with lung function, symptoms and airway inflammation. Methods: Serum IgG, IgA, IgE and IgM, IgG subclasses and FLC, and bronchoalveolar lavage sIgA were evaluated from 15 normal subjects, 9 mild and 22 severe asthmatics with similar atopic status. Asthma symptoms were obtained by questionnaire, and airway inflammation was assessed by immunostaining for five inflammatory cell types. Results: Immunoglobulin levels in all groups were generally within the normal range. However, IgA and IgG were lower in severe asthmatics than normal subjects (overall p = 0.006 and 0.02, respectively). IgA, but not IgG, correlated with lung function and asthma symptoms (r-values >0.58; p-values <0.009). Although similar among the groups, higher sIgA and IgG2 also positively correlated with lung function and negatively with asthma symptoms (r-values >0.63; p-values <0.009). IgA and IgG/IgG1 positively correlated with tissue mast cells. Conclusions: Subtle alterations in IgA- and IgG2-mediated responses in asthma may be disease-related. As their levels are generally normal, it is possible that the quality/repertoire of immune protection provided by these isotypes, perhaps against carbohydrate epitopes, may be altered in asthma.