Background: It is well-known that a group of Common Variable Immunodeficiency (CVID) patients actually suffer from late-onset combined immunodeficiency (LOCID), a different disease with a T-cell defect associated with a more aggressive clinical behavior. Different criteria have been proposed for diagnostic of LOCID (the DEFI and Freiburg criteria) based on naïve CD4+ T-cell frequency. However, these criteria have been arbitrarily established without considering age-related variations in the reference values for naïve CD4+ T cells. Aims: To validate a new age-matched criteria to better discriminate LOCID among patients with a CVID-like clinical phenotype.
Methods: A total of 157 CVID patients from 11 hospitals were studied in parallel to 270 healthy donors using the Euroflow PID Orientation tube (PIDOT).
Results: Using the new age-matched criteria, a higher number of LOCID patients was observed (n=56) vs. the Freiburg (n=35) and DEFI (n=21) classifications. The age-based criteria was particularly efficient to identify LOCID patients, among the 18-39y (36% vs. 23% and 9%; p<0.01) and 40-59y (46% vs. 28% and 19%; p<0.001) CVID age-groups. Frequency of infections were associated with IgG and IgA serum levels at diagnosis, but presence of non-infectious complications were exclusively found among individuals with low naïve CD4+ T-cell counts, independently of the LOCID criteria. However, the age-based criteria showed a higher sensitivity for identifying of patients suffering autoimmune cytopenia (66% vs. 41% and 24%), enteropathy (60% vs. 31% and 31%) splenomegaly (60% vs. 40% and 24%), hepatomegaly (69% vs. 42% and 35%), lymphadenopathy (71% vs. 49% and 27%), granulomas (70% vs. 44% and 25%) and interstitial lung disease (59% vs. 47% and 24%) than the Freiburg and DEFI criteria, respectively. Conclusions The new age-matched criteria to identify CVID patients with decreased naïve CD4+ T-cell counts provides a more accurate diagnosis of LOCID, associated with more severe clinical phenotypes.