Introduction: Previous studies have associated non-infectious complications with alterations of the profile of helper TCD4+ cells in common variable immunodeficiency (CVID) patients. However, these studies have not discriminated pure CVID from those patients suffering from an underlying CD4+ T-cell production defect (late-onset combined immunodeficiency -LOCID-) criteria. We aimed to evaluate the relationship between CD4+ T-cell compartment alterations and the clinical behavior of CVID and LOCID patients.
Methods: CD4+ T-cell subsets were analyzed in 53 CVID and 19 LOCID patients, in parallel with 146 healthy donors (4-88 years) using EuroFlow-based flow cytometry methods.
Results: Higher percentage of patients with decreased T-cell subset counts were observed in LOCID vs. CVID patients, including Treg (84% vs. 61% of patients respectively), Th2 (100% vs. 45%), Th17 (95% vs. 49%), and Th1/Th2 (63% vs. 28%), as compared to age-reference values. In contrast, few LOCID and CVID patients showed decreased TFH (5% and 2%), Th1 (21% and 20%), and Th1/Th17 (16% and 14%) counts. Multivariant analysis showed two clearly distinct subgroups of LOCID, those with higher Th1 counts presenting with a higher frequency of autoimmune cytopenia (100% vs. 22%, p=0.005) and interstitial lung disease (60% vs. 11%, p=0.04), together with lower frequency of non-respiratory infections (50% vs. 100%, p=0.02). In addition, four CVID subgroups were identified, one of them without alterations in the Th compartment and the others were identified based on Th1 and TFH cell alterations, with a significantly higher frequency of autoimmune cytopenia in CVID cases with higher Th1 cells (88% vs. 18% vs. 8% vs. 44%, p<0.001).
Conclusions: LOCID patients show more severe T-cell defects (Treg, Th2, Th17, and Th1/Th2) than CVID patients. Interestingly, autoimmune cytopenias were almost restricted to patients with expanded Th1 CD4+ T cells in blood, in both LOCID and CVID patients, together with higher prevalence of interstitial lung disease.