IPINeT Ped-unPAD Study: Goals, Design, and Preliminary Results

Abstract

Background: An unclassified primary antibody deficiency (unPAD) is a widely heterogeneous clinical entity, recently identified within the spectrum of Inborn Errors of Immunity (IEIs). Since unPAD has been traditionally considered as a mild condition, it has incorrectly received little attention, resulting in the paucity of extensive and comparable studies describing its natural history. To address the gaps in characterizing, understanding, and managing pediatric unPAD patients, the Italian Primary Immunodeficiency Network (IPINet) Ped-unPAD study has recently been launched. Methods: Seventeen IPINeT Centers have expressed interest to participate, and data collection is still on-going. Hereby, we anticipate preliminary key issues emerging from the first 110 enrolled patients, attending three IPINet Centers. Results: A proportion of unPAD patients have experienced a severe infectious phenotype, which required hospitalization in a quarter of patients and antibiotic prophylaxis or Immunoglobulin Replacement Therapy in approximately 10% of patients. In this partial cohort, a mean follow-up (FU) of 5 years confirmed unPAD diagnosis in fifty percent of cases, with the remaining being reclassified as the Transient Hypogammaglobulinemia of Infancy (25%) and other IEIs (25%), such as a Common Variable Immunodeficiency, Selective IgA deficiency, Selective IgM deficiency, and IgG3 subclass deficiency. Conclusions: Despite a phenotype overlap at diagnosis, clinicians should be aware that unPAD is a mutable condition that deserves comprehensive evaluation and long-term monitoring to dissect the final diagnosis for optimal treatment.

Keywords: children; common variable immunodeficiency; inborn errors of immunity; primary antibody deficiency; transient hypogammaglobulinemia of infancy; unclassified primary antibody deficiency.

Figure 1

Patient stratification according to reduced Ig isotype(s)/IgG subclasses.

Figure 2

Diagnostic reclassification of 110 unPAD patients at last FU: unPAD (clear blue), THI (green), IgMD (orange), CVID (red), SIGAD (grey), IgG subclass deficiency (yellow).

Figure 3

IEI evolution according to reduced Ig isotype(s)/IgG subclasses at diagnosis.