First Report from the Czech National Registry of Inborn Errors of Immunity (2012-2025) NUMBER OF WORDS: 3764 NUMBER OF TABLES: 9 NUMBER OF FIGURES: 6

Zita Chovancova¹Eva Hlavackova²Roman Hakl²Tomas Milota^3,4Pavlina Kralickova⁵Ivana Malkusova⁶Beata Hutyrova⁷Michaela Safarova⁸Jana Vydlakova⁹Dalibor Jilek¹⁰Jiri Novak¹¹Helena Schneiderova¹²Petra Kralova¹³Alena Zimulova¹⁴Vitezslav Novak¹⁵Jaromir Bystron¹⁶Dita Zaveska¹⁷Vendula Latalova¹⁸Frantisek Kopriva¹⁹Martin Kasl²⁰Vladimir Kracik²¹Renata Formankova²²Petr Sedlacek²³Karolina Vytiskova²⁴Michal Svoboda²⁴Hana Novakova²⁴Jiri Litzman^25*

• ¹Masaryk Universiry, Faculty of Medicine, Dept Clin Immunol. Allergol, St. Anne's University Hospital Brno, Brno, Czechia
• ²Masaryk University, Faculty of Medicine, Dept Clin Immunol. Allergol, St. Anne's University Hospital Brno, Brno, Czechia
• ³Second Faculty of Medicine, Department of Immunology, Univerzita Karlova, Prague, Czechia
• ⁴Fakultni nemocnice v Motole, Prague, Czechia
• ⁵Charles University in Hradec Kralove, Dept Clin Immunol. Allergol, Fakultni nemocnice Hradec Kralove, Hradec Kralove, Czechia
• ⁶Dept Allergol Clin Immunol, University Hospital Pilsen, Univerzita Karlova Lekarska fakulta v Plzni, Pilsen, Czechia
• ⁷Dept Allergol. Clin. Immunol., Fakultni nemocnice Olomouc, Olomouc, Czechia
• ⁸Chales University, First Faculty of Medicine, Institute of Immunology and Microbiology, Vseobecna fakultni nemocnice v Praze, Prague, Czechia
• ⁹Dept. Clin. Immunol. Allergol, Institut klinicke a experimentalni mediciny, Prague, Czechia
• ¹⁰Dept Clin Immunol Allergol, Masarykova nemocnice Usti nad Labem oz, Ústí nad Labem, Czechia
• ¹¹Centre Clin. Immunol., Nemocnice Ceske Budejovice a s, Ceske Budejovice, Czechia
• ¹²Masaryk University, Dept Pediatr, Fakultni nemocnice Brno, Brno, Czechia
• ¹³Dept. Allergol. Clin. Immunol., Fakultni nemocnice Kralovske Vinohrady, Prague, Czechia
• ¹⁴Dept. Pulmonary .Med., Krajska Nemocnice Tomase Bati as, Zlin, Czechia
• ¹⁵Dept. Immunol., Zdravotni ustav se sidlem v Ostrav, Ostrava, Czechia
• ¹⁶Dept. Allergol. Clin. Immunol., Fakultni nemocnice Ostrava, Ostrava, Czechia
• ¹⁷Charles University in Hradec Kralove, Faculty of Medicine,, Dept Pediatrics, Fakultni nemocnice Hradec Kralove, Hradec Kralove, Czechia
• ¹⁸Faculty of Medicine and Dentistry, Dept. Pediatrics, Univerzita Palackeho v Olomouci, Olomouc, Czechia
• ¹⁹Faculty of Medicine and Dentistry, Dept .Peditrics., Univerzita Palackeho v Olomouci, Olomouc, Czechia
• ²⁰Kasmed Ltd, Tabor., Tabor, Czechia
• ²¹Dept. Clin Mikrobiol, Imunol., Krajska Nemocnice Liberec as, Liberec, Czechia
• ²²Charles University, Second Faculty of Medicine, Dept. Pediatr. Hematol. and Oncol., Fakultni nemocnice v Motole, Prague, Czechia
• ²³Charles University, Second Faculty of Medicine, Dept Pediatr Hemtol. Oncol., Fakultni nemocnice v Motole, Prague, Czechia
• ²⁴Institute of Biostatistics and Analyses, Brno, Czechia
• ²⁵Masaryk University, Faculty of Medicine, Dept. Clin. Immunol .Allergol., St. Anne's University Hospital Brno, Brno, Czechia

Congenital immune system defects represent an ever-growing group of diseases characterized by increased susceptibility to infections and association with autoimmune, autoinflammatory, allergic and malignant complications. Here, we provide the first comprehensive report on inborn errors of immunity (IEIs) in Czechia based on the analysis of patient data from the Czech national registry (CzNR) of IEIs.The online platform of CzNR of IEIs was established in 2012, compiling data about epidemiology, type of diagnosis, clinical and laboratory parameters, as well as the treatment of patients diagnosed with IEIs since 1981.The total of 1,443 registered patients includes 697 males (48.3%) and 746 females (51.7%). The median age at diagnosis was 21.0 (0-86) years. The most represented group of patients was those with antibody deficiencies (No=788; 54.6%). This was followed by complement deficiencies (No=242; 16.8%), combined immunodeficiencies with syndromic features (No=250; 17.3%), combined immunodeficiencies (No=55; 3.8%), congenital defects of phagocyte number, function, or both (No=31; 2.1%), autoinflammatory disorders (No=28; 1.9%), immune dysregulation diseases (No=24; 1.7%), intrinsic and innate immunity defects (No=21; 1.5%), primary immunodeficiency phenocopies (No=3; 0.2%), and bone marrow failure disorders (No=1; 0.1%). Common variable immunodeficiency (No=504; 34.9%), hereditary angioedema (No=222; 15.4%), and DiGeorge syndrome (No=182; 12.6%) were the most frequent diagnoses.In this article, we report the epidemiology of IEIs in the Czech Republic for the first time based on the CzNR of IEIs data. The prevalence of IEIs is approximately 13.2 patients per 100000 inhabitants of the Czech Republic. psychiatric medication (primarily clozapine). A separate section was dedicated to the treatment of hereditary angioedema (HAE) attacks. Patients with multiple overlapping phenotypes were entered into the registry according to their primary diagnosis based on the IUIS classification, even if they suffered from additional associated immunopathological complications.The Czech Republic, located in Central Europe, has nearly 11 million inhabitants and an area of 78,866 km 2 . It is divided into 14 self-governing regions. Almost all regions have medical facilities that provide care for patients with PIDs/IEIsIEIs and contribute data to the CzNR of PIDs/IEIsIEIs.