Notably, a retrospective comparison of the clinical and immunological features in the diagnosis of persistent IEI vs. THI cohorts allowed us to identify the following relevant clues of IEI persistence: (I) age at diagnosis > 4 years, (II) history of RRTI and pneumonia, (III) hospitalization due to serious infections and, particularly, to pneumonia, (IV) an isolated or combined IgM deficiency, (V) combined deficiency of IgA and IgM, (VI) combined IgG, IgA, and IgM defect, (VII) low anti-PCP antibody response, and (VIII) low switched memory B cells. Here, CD40LG is linked to infection.