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Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI., Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174)., Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abolhassani, Avcin, Bahceciler, Balashov, Bata, Bataneant, Belevtsev, Bernatowska, Bidló, Blazsó, Boisson, Bolkov, Bondarenko, Boyarchuk, Bundschu, Casanova, Chernishova, Ciznar, Csürke, Erdős, Farkas, Fomina, Galal, Goda, Guner, Hauser, Ilyina, Iremadze, Iritsyan, Ismaili-Jaha, Jesenak, Kelecic, Keles, Kindle, Kondratenko, Kostyuchenko, Kovzel, Kriván, Kuli-Lito, Kumánovics, Kurjane, Latysheva, Latysheva, Lázár, Markelj, Markovic, Maródi, Mammadova, Medvecz, Miltner, Mironska, Modell, Modell, Mosdósi, Mukhina, Murdjeva, Műzes, Nabieva, Nasrullayeva, Naumova, Nagy, Onozó, Orozbekova, Pac, Pagava, Pampura, Pasic, Petrosyan, Petrovic, Pocek, Prodeus, Reisli, Ress, Rezaei, Rodina, Rumyantsev, Sciuca, Sediva, Serban, Sharapova, Shcherbina, Sitkauskiene, Snimshchikova, Spahiu-Konjusha, Szolnoky, Szűcs, Toplak, Tóth, Tsyvkina, Tuzankina, Vlasova and Volokha.)

Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.