Clinical and immunological differentiation of isolated IgG and combined IgG & IgM deficiencies from common variable...

To assess the clinical relevance of diagnosing and classifying isolated IgG deficiency and combined IgG/IgM deficiency separately from CVID.

In a retrospective cohort of patients with primary hypogammaglobulinemia, we evaluated and compared the clinical spectrum and immunological findings of patients with CVID, isolated IgG deficiency, and combined IgG/IgM deficiency.

In comparison to CVID, respiratory tract infections and gastrointestinal infections were less common in isolated IgG or combined IgG/IgM deficiency, while recurrent mucocutaneous herpes simplex virus reactivations were more common. With respect to immune dysregulation, splenomegaly and immune thrombocytopenic purpura were more frequently observed in CVID. Comparison of immunophenotypic data, revealed relatively lower class-switch memory B cell counts in CVID, while patients with IgG deficiency displayed lower transitional B cells. Survival analysis for these cohorts reveals a significant divergence in long-term outcomes, demonstrating that patients with CVID experience markedly lower overall survival rates.

Comparison of CVID with isolated IgG deficiency or combined IgG/IgM deficiency revealed distinct immunophenotypic profiles, differences in both infectious and non-infectious manifestations, and markedly worse clinical outcomes in CVID. These findings suggest that CVID and unclassified antibody deficiencies - manifesting as isolated IgG deficiency or combined IgG/IgM deficiency - occupy different immunological niches. Consequently, our data support maintaining CVID as a distinct diagnostic entity, separate from IgG and IgG/IgM deficiencies, and highlight the need for tailored diagnostic approaches and follow-up strategies for these different forms of primary antibody deficiency.