Frequency and clinical spectrum of immune dysregulation in primary immunodeficiencies: experience of a single Central European Adult Care Centre

Abstract

Primary immunodeficiencies (PIDs) encompass not only recurrent infections but also a wide range of manifestations of immune dysregulation, including autoimmunity, lymphoproliferation, granulomatous disease, and malignancies. The aim of the study was to analyse the prevalence and clinical features of immune dysregulation among adult patients with PID, and to evaluate the relationship between age at diagnosis, diagnostic delay, and the development of non-infectious complications. We retrospectively reviewed the records of 28 adult patients with PID receiving immunoglobulin replacement therapy. Features of immune dysregulation were analysed in relation to age at diagnosis and diagnostic delay. We were able to diagnose PID in 28 patients (estimated prevalence of adult-onset PID in the area of our centre is 3.01/100.000), among these, the most common group was primary antibody deficiency (PAD: 25/28, 89%). Immune dysregulation was observed in 22 patients (79%), three of whom presented without any infectious manifestations. The prevalence of autoimmune disease was significantly higher among patients diagnosed after the age of 50 than among those diagnosed in childhood (58% vs. 0%, p = 0.0377). ROC analysis identified age ≥ 41 years at diagnosis as a significant discriminator of immune dysregulation-related complications (AUC = 0.724, p = 0.025). Malignancy accounted for half of all deaths (3/6, 50%), while no patient died of infection. Immune dysregulation represents a hallmark of adult-onset PID, often preceding or occurring independently of recurrent infections. Malignancy, rather than infection, emerged as the leading cause of death. The observed gap between expected and diagnosed prevalence highlights an unmet need for improved recognition of PID in adults and better transition pathways from paediatric to adult care in Central and Eastern Europe.