In Italy, genetic testing for inborn errors of immunity (IEI) is currently performed either at one of the Academic University Hospitals or IRCSS (Istituti di Ricovero e Cura a carattere Scientifico) with a Medical Genetics Department, or at accredited private genetics laboratories. The Department of human genetics of Academic institutions specialized in the diagnosis and therapy of IEI, are considered referral centers for the interpretation of IEI genomic data. In Italy, genetic counselling should precede and follow a genetic testing (pre-test and post-test) as recommended by the Ministry of Health. The diagnostic report must be signed by a geneticist with Medical Genetics specialty.
In Italy, health insurance is not currently mandatory. Patients are covered by public assistance and citizens who have a private health insurance represent a minority. The Italian National Health System (SSN) provide assistance through 21 partly independent Regional Health System (SSR). In Italy, by law, region will pay for the genetic analyses of patients under the strong suspicion of an IEI, covering the full cost of the analysis under exemption for rare diseases. The National Plan for Rare diseases (2023-2026), which includes IEI, foresees an integrated model according a design which is multicentric and multidisciplinary across different national centres. However, there is disparity in terms of mobility across Regions as some Regions allow it for treatment but not for diagnostic testing. In fact, genetic testing might be performed in specialized centres from other Regions.
NGS panels and CES (clinical exome sequencing) are covered by NHS assistance. The cost is approximately 4.000€ per trio analysis and 1500€ per single CES, but may vary depending whether performed by a public or private center. Pre-test counselling may be offered either by a geneticist, or a pediatrician or an immunologist with expertise in genetic. The specialist prescribes the test and acquires the informed consent. For refugees with no health assistance, genetic testing might be more difficult to perform, although in principle a 6-month temporary card may allow genetic testing.
In the context of research projects, laboratories can provide genetic testing, which is covered by project funding. Research projects could be: a) specific for primary immunodeficiencies and include immunological studies as well, or b) genetic-based centred for the diagnosis of unsolved and complex cases that require a multidisciplinary approach, thus open to physicians from different areas (genetics, neurology, immunology,etc.). Funding is mainly covered by Ministry of Health, Ministry of University and Research or other national/international institutions on a competitive basis (usually for a 2-5-year funding). The IRCCS pediatric network (RETE IDEA) receives funding in a dedicated call from the Ministry of Health.
Results are classified either as disease causing, disease associated, or as a variant of unknown significance. In the last case, the physician in charge has the opportunity to consult the “list of functional testing” (https://ern-rita.org/working-group/molecular-testing/) of the European reference network RITA (https://ern-rita.org/) to receive laboratory support in the interpretation of findings. For data protection reasons, laboratory results can only be communicated to the submitting physician.
A genetic diagnosis of IEI is usually communicated to the patients during a post-test genetic counselling to the patients or their guardians. Only physicians educated in the genetics of inborn errors of immunity or geneticists may communicate the genetic results to the patients or their guardians.
