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Background: Newborn screening (NBS) for the early detection of inborn errors of immunity (IEI) has been implemented in a few countries. The objective of this study was to verify the situation and define obstacles to the implementation of NBS worldwide. Methods: A questionnaire was developed by the Inborn Errors of Immunity Committee of the World Allergy Organization (WAO) with 17 questions regarding NBS for IEI in the physician's workplace, NBS test type, problems hindering NBS implementation, reimbursement for IEI therapy, presence of a national IEI registry, referral centers, molecular diagnosis, hematopoietic stem cell transplantation centers, gene therapy, and immunoglobulin replacement therapy. The survey was sent by email once a week to doctors and others associated with WAO and the main immunology societies worldwide as a Google Form™ to be completed during September and October 2021. Results: Two hundred twenty-nine questionnaires were completed, of which 216 (94.3%) were completed by physicians. One hundred seventy-six (76.8%) physicians were both allergists and immunologists. The agreement between allergists/immunologists and non-allergists/non-immunologists for the question “Is there NBS for IEI in the country you work in?” was good (κ = 0,64: 95% CI 0.55–0.69). Ninety-eight (42.8%) participants were from Latin America, 35 (15.3%) from North America, 29 (12.6%) from Europe, 18 (7.9%) from Africa, 44 (19.2%) from Asia, and 5 (2.2%) from Oceania. More than half the participants (n = 124, 54.2%) regularly treated patients with IEI, followed by occasional treatment (n = 77, 33.6%), or never (n = 28, 12.2%). Of the respondents, 14.8% reported that their countries performed NBS for IEI, whereas 42.2% reported their countries did not. T-cell receptor excision circles was the most widely used technique in some countries, with 75 (59.9%) for the diagnosis of NBS for IEI, followed by combined use with kappa deleting-recombination excision circles. Only 13 participants (10.3%) underwent neonatal exon screening in their respective countries. Financial and technical issues were among the major obstacles to the implementation of NBS for IEI. Conclusions: This pilot study showed that few countries have implemented NBS for IEI, despite the presence of immunology referral centers and the availability of hematopoietic stem cell transplantation and intravenous immunoglobulin replacement therapy. The findings highlight the difficulties, mainly financial and technical, hindering wide application of NBS. Sharing experiences, technologies, and resources at the international level can help overcome these difficulties.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total of 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10–28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3–11.3%) had bronchial asthma, 3.6% (1.9–9.1%) atopic dermatitis, 3.0% (1.0–7.8%) allergic rhinitis, and 1.3% (0.5–3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5–25%) and diagnosis delay was reported in 7.5% (0.9–20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2–62.5%) and 20.0% (10–32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Primary immunodeficiency diseases (PIDs) are genetically inherited diseases characterized by an increased susceptibility to infections, autoimmunity, lymphoproliferation, and malignancies. PIDs are under-diagnosed and the registered cases and reported prevalence are far below the estimated numbers especially in countries with large population and high consanguinity rates. Delays in diagnosis yield major morbidities and mortalities with resultant increased economic burden. Newborn screening using TRECs and KRECs, currently being implemented in some countries, is aimed through early diagnosis, to overcome the delays in the diagnosis and hence the poor outcome of some of the severe PIDs. However, the limited resources in developing countries challenges the implementation of newborn PID screening programs. There are considerable gaps in our knowledge that must be bridged. Setting the norms of TRECs and KRECs for each country is needed. Furthermore, some PIDs that might present in the neonatal period could not be detected by the current screening programs, and their diagnosis requires clinical expertise. Not to mention, local guidelines for the management of patients diagnosed by NBS should be set forth. Also, in the absence of NBS, clinicians should be aware of the early manifestations of PID. All these mandate conducting studies genuine to each country, developing programs for raising public awareness and clinical training of physicians to attain the required immunological skills.