The Evolutionary Scenario of Pediatric Unclassified Primary Antibody Deficiency to Adulthood

Sgrulletti M, Costagliola G, Giardino G, Graziani S, Del Duca E, Di Cesare S, Di Matteo G, Consolini R, Pignata C, Moschese V.

Background: Unclassified primary antibody deficiency (unPAD) is a relatively novel inborn error of immunity (IEI) condition that can vary with time to more defined entities. Since long-term follow-up (FU) studies are scarce, we aimed to provide insight into the evolutionary clinical and immunological scenario of unPAD children to adulthood and identification of biomarkers of primary immune deficiency (PID) persistence.

Methods: A total of 23 pediatric unPAD patients underwent clinical and immunological FU for a mean time of 14 years (range 3-32 years, median 16 years).

Results: UnPAD diagnosis may change over time. At the last FU, 10/23 (44%) children matched the diagnosis of transient hypogammaglobulinemia of infancy and 13/23 (56%) suffered from a persistent PID. In detail, an unPAD condition was confirmed in 7/23 (30%) patients, whereas 3/23 (13%), 2/23 (9%), and 1/23 (4%) were reclassified as common variable immunodeficiency, selective IgA deficiency, and isolated IgM deficiency, respectively. Low IgA, low specific antibody response to pneumococcus, and lower respiratory tract infections at diagnosis were independently associated with IEI persistence.

Conclusions: Long-term monitoring of unPAD patients is required to define their outcome and possible evolution towards a definitive IEI diagnosis.

Keywords: TNFRSF13B mutations; children; common variable immunodeficiency; inborn errors of immunity; isolated IgM deficiency; primary antibody deficiency; selective IgA deficiency; transient hypogammaglobulinemia of infancy; unclassified primary antibody deficiency.

Clin Med. 2023