D2.124 - Clinical Significance of Humoral Immunodeficiency in Patients with Severe Asthma

Reduced circulating total immunoglobulin G (IgG) or IgG subclass levels have been associated with recurrent respiratory tract infections, increased exacerbations, and higher mortality in patients with chronic obstructive pulmonary disease. However, the prevalence and clinical significance of humoral immunodeficiency in patients with severe asthma have not been well investigated. This study aimed to evaluate the prevalence of humoral immunodeficiency and its associated clinical characteristics in patients with severe asthma using the data from the Korean Severe Asthma Registry (KoSAR).

Total IgG, IgA, IgM, and IgG subclass levels were measured in 313 patients enrolled in KoSAR who were regularly followed for one year. IgG subclass deficiency (IgGSCD) was defined as deficiency in any IgG subclass documented on at least two separate measurements. Clinical parameters and outcomes such as lung function, exacerbation, and oral corticosteroid (OCS) use were compared between patients with and without IgGSCD.

Among patients with severe asthma (n=313), six patients showed hypogammaglobulinemia, and 38.7% (n = 121) had IgGSCD, IgG3 deficiency was the most common (n = 110, 35.1%), followed by IgG2 deficiency (n = 35, 11.2%). Patients with IgGSCD tended to experience more frequent moderate-to-severe exacerbations at baseline and at 12 months follow-up, however, these differences were not statistically significant. Especially, the number of severe exacerbations was higher in patients with IgGSCD experienced than those without IgGSCD (1.52 ± 2.15 vs. 1.10 ± 1.71, P = 0.071). In addition, cumulative OCS dose (prednisolone-equivalent) over one year was significantly higher in patients with IgGSCD compared with those without IgGSCD (1762.71 ± 1984.28 mg vs. 1110.00 ± 1055.92 mg, P = 0.030). Patients with IgGSCD showed lower blood eosinophil percentages and more frequent use of macrolide antibiotics (P = 0.022 for both). Among IgG subclass deficiencies, IgG2 deficiency was associated with the highest frequency of severe exacerbations and greatest cumulative OCS exposure. 

Humoral immunodeficiency, particularly IgGSCD, is common in patients with severe asthma and is associated with increased disease burden. IgGSCD may represent a clinically relevant and potentially treatable trait in severe asthma.