Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

Abstract

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.

Clinical exome sequencing data from patients with inborn errors of immunity: cohort level meta-analysis and the benefit of systematic reanalysis

“…The molecular diagnostic rate in our cohort is limited, mainly owing to patient characteristics, including a predominantly adult population with late disease onset, high proportion of disease categories with a lower chance of monogenic findings, and the inclusion of less severe immune phenotypes where ES is used to rule out an IEI. The distribution of patient phenotypes differs from those in the large patient registry for IEI from the European Society for Immunodeficiencies, which includes a higher percentage of patients with PAD and lower percentages of patients with immune dysregulation, defects in intrinsic immunity and autoinflammatory disease (97). Nevertheless, our cohort reflects clinical practice with an unselected, cross-sectional cohort and a wide array of disease manifestations.…”

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders

“…Recent guidelines in the field of primary immunodeficiency have recommended rigorous screening for primary immunodeficiency if two or more warning signs are present in patients with recurrent infections [31]. As each of our five patients showed two or more warning signs, we propose to include immunological assessments (complete blood count, immunoglobulins, T/B/NK subsets with FACS) at initial presentation and/or diagnosis of a PUF60-related disorder to assess for any signs of immunodeficiency, especially with a patient history of recurrent infections [35][36][37][38].…”