Advances in Primary Immunodeficiencies (Inborn Errors of Immunity) in Central-Eastern Europe: Volume II. (2023)

Malgorzata Pac^1*, Jean-Laurent Casanova^{2, 3, 4, 5}, Irina A. Tuzankina⁶ and László D. Maródi^{2, 7}

tremendous role of International Union of Immunological Societies (IUIS) and its Expert Committee updating categorization of IEI approximately every 2 years. According to the last 2022 report 485 different genetic defects causing IEI are known (55 novel comparying to 2019 report), categorized as previously into 10 groups and published as phenotypical classification as well. Taking into account that number of all IEI remains underestimated all the efforts of enthusiastic doctor and scientists to improve diagnostics, recognition and treatment is of great value. 1,2,3 . The progress in the field of clinical and experimental immunology was done over the past decades mainly in Western Europe, the USA, Japan, and Australia [1][2][3][4][5] , also with significant contributions from Latin America, Africa, the Middle East, and both South and East Asia. Eastern and Central European (ECE) countries have remained isolated for many years, until the fall of the iron curtain in 1989, with limited access to the newest scientific achievements, diagnostic tools, and therapeutic methods. Only personal connections, and direct collaboration with clinical and research centers in Western Europe and the US, made some progress possible in that region. Within the last 30 years a lot of efforts let overcome the gap between ECE and Western Europe in terms of IEI diagnostics, including molecular tests, treatment, and education. One of the most important initiative was the J Project, initiated in 2004 by the clinicians and scientists in Eastern and Central Europe. The goal of JProject (JP) was to increase awareness, facilitate diagnosis including genetic tests, and improved therapy according to the latest knowledge in the area of ECE region. During the next years collaboration expanded to include in "daughter J Projects" such countries like Turkey, Iran, Egypt, Russia and others. [5][6][7][8][9][10] Between the end of 2019 and 2020 we succesfully published 11 manuscripts as an e-book dedicated to "Advances in Primary Immunodeficiencies (Inborn Errors of Immunity) in Central-Eastern Europe", covering the results of clinical and scientific work in the separate countries in the region as well the effects of JP network 11 . One year later we decided to edit the second volume of special research topic: "Advances in Primary Immunodeficiencies (Inborn Errors of Immunity) in Central-Eastern Europe" to expose the successful efforts of single immunological centers or countries as well as the effects of scientific collaboration within ECE region, and Western Europe and/or the US in the field of IEI. Finally after standard review process, 19 articles reflecting new diagnostic tools, their influence on recognition of IEI, country-related registries, analysis of clinical course of known and novel IEI and mutations as well as treatment were selected for publications.In March 2020 World Health Organization (WHO) announced COVID-19 pandemics affecting people all over the world regardless age, sex or comorbidities, with worse prognosis within an older people with type I interferon autoantibodies or concominant diseases. Patients with IEI also appeared to be at higher risk of developing COVID-19 at the beginning.However further observations from different centers showed that only certain types of IEI are associated with poor prognosis [12][13][14][15][16][17][18][19] In mini review Nikolouli et al provided analysis of the currently available in vitro models used to study IEI and its role for new therapeutic approaches.Following the world trend to make recognition of severe combined immunodeficiencies as well as other severe T or B lymphopenia as soon as possible, the pilot study results from Ukraine was published. TREC and KREC analyses were done in almost 10 500 newborn for severe combined immunodeficiency (SCID) and other severe IEI with one case of CID detected. The DNA samples from known IEI (SCID, CID, XLA) were used as controls. The study proved that newborn screening for SCID and other severe IEI let introduce proper treatment procedures such as HSCT and IgRT before the first symptoms and complication occurred.Selected papers described new genetic causes of different inborn errors of immunity, such as STIM1 GOF mutation, GATA2 defect. Other reports concerned rare and not typical manifestation of known gene defects, including LIG1 deficiency and Omenn-like syndrome, SRP54 deficiency and cyclic neutropenia or Pneumocystis jirovecii pneumonia in Aicardi-Goutieres syndrome.Different clinical aspects, such as pulmonary lesions or sleep quality or fatigue assessment in adult patient with humoral defects and other primary immunodeficiencies were discussed by Polish authors.The essential issues of an advancement in early diagnostics and treatment of ADA-SCID patients were presented in multicenter report from Poland. It showed limitations of enzyme replacement therapy due to high costs and lack of approval in EU and restricted access to gene therapy. It indicated that implementation of newborn screening program for SCID in Poland could improve early recognition and treatment of all SCID, including ADA-SCID.There was also space to discuss experimental aspects of human hepatocyte transplantation for liver disease.It should be emphasized that published papers document a substantial improvement of IEI awareness and research in the Central and Eastern Europe. The increased awareness of IEI led to better and quicker recognition, including new gene mutation in different IEI, introducing new diagnostic tools and treatment approaches, as well as better understanding of IEI-related complications or mechanisms, as shown in the collection of Research Topic.The Editors hope that the second edition of Special Issue: "Advances in Primary Immunodeficiencies (Inborn Errors of Immunity) in Central-Eastern Europe" will give the readers an opportunity to learn more about the remarkable development in the ECE region on IEI-related specific diseases, their molecular background, novel mutations in different phenotypes. It should also stimulate further research and cooperation within the J Project in ECE countries and elsewhere in this rapidly developing field of molecular medicine. Finally we are grateful to the Editors of Frontiers in Immunology for their invitation to put together this Issue.