Când trebuie să ne gândim la imunodeficiența primară?

Summary. Primary immunedeficiencies (PIDs) are rare disorders, with discordant statistics regarding their reported prevalence (dependent on population, country, PID center): 1.51/100,000 (Germany), 4.97/100,000 (France), 12.4/ 100,000(Australia), 10/100,000 (worldwide), 80-100/ 100, 000 inhabitants (EDQM). It is estimated that 1% of the global population has PID and > 6 million persons suffer from PID worldwide, 70-90% of them remaining undiagnosed (I. Meyts, 2021; JM Boyle, 2007).Rezumat. Imunodeficiențele primare (IDP) sunt tulburări rare, cu statistici discordante în ceea ce privește prevalența raportată (în funcție de populație, țară, centru PID): 1,51/100.000 (Germania), 4,97/100.000 (Franța), 12,4/ 100.000 (Australia), 10/100.000 (în toată lumea), 80-100/ 100.000 locuitori (EDQM). Se estimează că 1% din populația globală are BIP și > 6 milioane de persoane suferă de BIP la nivel mondial, 70-90% dintre ele rămânând nediagnosticate

RNA sequencing suggests that non-coding RNAs play a role in the development of acquired haemophilia

Funding Information: Adrian Bogdan Tigu and Ionut Hotea contributed equally to the current manuscript and are both considered first author. The authors also gratefully acknowledge the support of Sergiu Pasca, M.D. – Johns Hopkins University School of Medicine, Baltimore, United States, for his contribution on the statistical analysis. Funding Information: IH is funded by an internal grant of the Iuliu Hatieganu University – School of Doctoral Studies. BT is supported by a national grant of the Romanian Academy of Scientists (Academia Oamenilor de Stiinta din Romania) 2023–2024. ABT, DG, JTB and VG are supported by an international collaborative grant of the European Economic Space between Romania and Iceland 2021–2023: ‘Cooperation strategy for knowledge transfer, internationalization and curricula innovation in the field of research education at the 3rd level of study –AURORA.’. The experiments were funded by an international grant awarded by the Novo Nordisk Haemophilia Foundation to the Romanian Haematology Society—Romania 4. CT is supported by a grant by grants awarded by the Romanian National Ministry of 350 Research, Innovation, and Digitalisation: Project PN‐III‐P4‐ID‐PCE‐2020‐1118. Publisher Copyright: © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Acquired haemophilia (AH) is a rare disorder characterized by bleeding in patients with no personal or family history of coagulation/clotting-related diseases. This disease occurs when the immune system, by mistake, generates autoantibodies that target FVIII, causing bleeding. Small RNAs from plasma collected from AH patients (n = 2), mild classical haemophilia (n = 3), severe classical haemophilia (n = 3) and healthy donors (n = 2), for sequencing by Illumina, NextSeq500. Based on bioinformatic analysis, AH patients were compared to all experimental groups and a significant number of altered transcripts were identified with one transcript being modified compared to all groups at fold change level. The Venn diagram shows that haemoglobin subunit alpha 1 was highlighted to be the common upregulated transcript in AH compared to classical haemophilia and healthy patients. Non-coding RNAs might play a role in AH pathogenesis; however, due to the rarity of HA, the current study needs to be translated on a larger number of AH samples and classical haemophilia samples to generate more solid data that can confirm our findings.Peer reviewe

Efficacy and Safety of Hizentra®, a New 20% Immunoglobulin Preparation for Subcutaneous Administration, in Pediatric Patients with Primary Immunodeficiency

Subcutaneous IgG treatment for primary immunodeficiencies (PI) is particularly well suited for children because it does not require venous access and is mostly free of systemic adverse events (AEs). In a prospective, open-label, multicenter, single-arm, Phase III study, 18 children and five adolescents with PI were switched from previous intravenous (IVIG) or subcutaneous (SCIG) IgG treatment to receive dose-equivalent, weekly subcutaneous infusions of Hizentra® for 40 weeks. Mean IgG trough levels were maintained in patients previously on SCIG, or increased in those previously on IVIG, regardless of age. No serious bacterial infections were reported during the efficacy period of the study. The rates of non-serious infections were 4.77 (children) and 5.18 (adolescents) infections per patient per year. Related AEs were observed in seven children (38.9%) and two adolescents (40%). Three serious AEs and two AEs leading to discontinuation (all unrelated) were reported in children. Hizentra® is an effective and well-tolerated treatment for pediatric patients

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

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

Our experience with orthopedic surgery in hemophiliacs

Introduction: Patients having severe hemophilia (levels of deficient factor below 1%) frequently suffer from disabling chronic arthropathy. An adequate substitution treatment using the coagulation factor VIII or IX concentrates renders an elective surgery feasible. Objective: The objective of the study was to check the results of different surgical procedures in the treatment of hemophilic arthropathies, and to propose the best protocol of their treatment. Methods: This is a retrospective study on 26 hemophilic patients operated in the Orthopedics and Trauma Clinic II, Timisoara, from 2002 to 2005. Elective surgical procedures were mainly performed in the knee (21 arthroscopic procedures, 1 open arthrodesis), elbow (2 open synovectomies, 2 radial head excisions), ankle (1 arthroscopic synovectomy and debridement) and thigh (1 giant pseudo tumor excision, other minor procedures). The results after operations on moderate and severe chronic knee, elbow and ankle arthropathy were evaluated, with approximately 24-month follow-up period. Results: Arthroscopic procedures (22) yielded good and satisfactory results with significant improvement according to the evaluation criteria recommended by the World Hemophilia Federation (Gilbert clinical score, Pettersson radiological score, NUSS MRI score). Conclusion: Mini-invasive elective surgery in moderate to severe chronic arthropathy produces good results when performed in a specialized center and with multi-disciplinary approach

MINIMAL INVASIVE ORO-DENTAL PROCEDURES – RECOMMENDATIONS FOR OPTIMAL CARE IN CHILDREN WITH HAEMOPHILIA

Oral and dental treatments are an essential condition for a good quality of life for hemifiliacs. Hemophilia is a hereditary disease that is manifested in male subjects and consists in lifelong alteration of antihemorrhagic mechanisms. Clinical investigations show that a significant percentage of haemophiliacs are diagnosed with bleeding of the oral and periodontal mucosa during both prosthetic and dental morphology restoration maneuvers. Small dental surgery procedures such as anesthesia, extirpation of dental pulp and other surgical procedures require pre- and postoperative treatment with Factor VIII or factor IX. The authors present steps that are indicated to be performed before, during and after dental treatments that can cause bleedings in the oral cavity. The area and mode of use of alternative or complementary hemostatic therapy is also presented, as well as the precautions required during local anesthesia. In conclusion, it can be said that people with haemophilia or congenital bleeding tendencies are a priority group for dental and oral health care, since bleeding after dental treatment may cause severe or even fatal complications. Maintenance of a healthy mouth and prevention of dental problems is of great importance, not only to quality of life and nutrition, but also to avoid the dangers of surgery

Pitfalls in hemostasis exploration, a case report of a girl with Henoch-Schönlein type vasculitis

The adequate performance and correct interpretation of assays for coagulation factor inhibitors play a critical role for the hemostasis laboratory. Both, false positive and false negative inhibitor assays may be reported, leading to erroneous patient’s management. Therefore, we decided to present a case with a spurious image of an exceptionally rare acquired combined haemophilia A, B and C, with severe factor ( F) VIII, IX and XI deficiency, associated with high titre anti - F VIII, IX and XI inhibitors in a 4 years old girl with Henoch-Schönlein type vasculitis. Finally, performing, beside coagulometric methods also antigenic ELISA assays, we had to invalidate the diagnosis. The performance of antiphospholipd antibodies clarified the diagnosis , finally concluding as definite diagnosis Transient Lupus Anticoagulant Syndrome, with decisive impact on therapy and follow-up

Pharmacoeconomic Analysis of Hemophilia Care in Romania

Hemophilia, a congenital X linked disease, has the serious burden of bleeding, requiring life-long replacement with coagulation factors (CF). In the present day, there is a continuously improving treatment for this condition. Objective: Our observational, cross-sectional study aims at finding out whether a prophylactic replacement with CF is affordable from the point of view of its cost-effectiveness in our country. Material and methods: A cohort of 122 persons with hemophilia were included in this patient-reported outcome survey, and they answered a questionnaire consisting of 56 items, focused on 4 domains—socio-demographic, medical, quality of health/life and cost/cost-effectiveness. Results and discussion: The markers for quality of health/life were correlated with the direct and indirect costs of care, comparing subgroup 1 of patients with prophylactic vs. subgroup 2 with on-demand replacement. Based on the incremental quality adjusted life years and the incremental costs, we calculated the incremental cost-effectiveness ratio (ICER) proving that prophylaxis is more cost-effective than on-demand replacement on a long time basis. Conclusions: The ICER is a threshold recommending the reimbursement of costs for a life-long prophylactic replacement in our country