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.
ABSTRACT
PURPOSE: Inborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. This study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI. METHODS: Here, we describe the functioning of the IEI-Virtual Consultation System (VCS), an innovative platform created by the Italian Immunodeficiency Network (IPINet). RESULTS: In the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. A final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis. CONCLUSION: From our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. These results may help the functioning of other international platforms for the management of complex cases.