DataSheet_1_Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.docx

IntroductionThe 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.ResultsIn 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).Conclusions1) 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.

引言
J 项目（JP）医师教育及临床研究协作计划始于2004年，至今已涵盖32个国家，主要位于东欧和中欧地区（ECE）。截至2021年底，JP 已组织了344场针对先天性免疫缺陷（IEI）的会议，旨在提高对IEI患者的认知，并促进其诊断和治疗。结果
在本研究中，我们分析了会议概况以及主要的诊断和治疗参数。JP中心的领导者们提供了来自30个国家的患者数据，总人口达到5,065,675,650人。其中两个国家报告了来自JP中心的IEI患者数据（土耳其的科尼亚和埃及的开罗大学）。诊断标准基于IUIS专家委员会于2020年更新的IEI分类。JP会议的数量从2004年和2005年的每年6场增加到2020年和2021年的44场和63场。各国累计会议数量从1场到59场不等，这在一定程度上反映了各自国家的人口状况，但并非完全如此。总计报告了24,879名患者，平均患病率为4.9%。大多数患者为抗体缺陷（46.32%），其次是联合免疫缺陷患者（14.3%）。骨髓衰竭和IEI表型患者的比例均不到1%。在13个国家中，患者数量显著高于ESID登记处的报告。7,572名患者接受了免疫球蛋白（IgG）替代治疗（其中5,693例为静脉注射），1,480名患者接受了造血干细胞移植（HSCT）。对基本诊断参数的搜索发现，免疫化学和流式细胞术在27个和28个国家可用，靶向基因测序和下一代测序在21个和18个国家可用。IEI中心和领域的专家数量分别为260和690。我们发现IEI中心数量与接受静脉免疫球蛋白（IVIG）治疗的患者数量（相关系数，cc，0.916）以及接受HSCT治疗的患者数量（cc，0.905）之间存在高度相关性。当比较专家数量时，也发现了类似的关联。然而，仅接受皮下免疫球蛋白（SCIG）治疗的患者数量与专家数量（cc，0.489）仅有轻微相关性，且中心数量与SCIG患者的数量之间没有发现相关性。结论
1) 这项研究首次描述了JP国家IEI护理的主要诊断和治疗参数；2) 数据表明，JP对东欧和中欧地区IEI护理的发展产生了巨大的影响；3) 我们的数据有助于确定JP在各国活动的主要未来目标；4) 我们提出，IEI中心和IEI专家的数量与最重要的治疗参数密切相关；5) 我们建议，在医疗专业人员中开展专科教育对于提高诊断水平和确保这一脆弱且仍被高度忽视的患者群体的适当护理起着关键作用；6) 本研究还为JP国家IEI护理的更多具体方面的进一步分析提供了基础，包括遗传诊断、疾病特异性患病率、新生儿筛查以及JP国家的专业合作。