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Systematic review of literature and analysis of big data from the national health insurance system on primary immunodeficiencies in Korea.

Clin Exp Pediatr. 2020 Jul 13;:

Authors: Son S, Kang JM, Hahn Y, Ahn K, Kim YJ

Abstract
There are very scant data on the epidemiology of primary immunodeficiency diseases (PIDs) in Korea. Here we attempted to estimate the PID epidemiology and disease burden in Korea. A systematic review was performed of studies retrieved from the PubMed, KoreaMed, and Google Scholar databases. Studies on PIDs published in Korean or English between January 2001 and November 2018 were analyzed. The number of PID patients and the healthcare costs were estimated from Health Insurance Review and Assessment Service (HIRA) Korea data for 2017. A total of 398 PID patients were identified from 101 reports. Immunodeficiencies affecting cellular and humoral immunity were reported in 11 patients, combined immunodeficiency with associated or syndromic features in 40, predominantly antibody deficiencies in 144, diseases of immune dysregulation in 58, congenital defects of phagocytes in 104, defects in the intrinsic and innate immunity in 1, auto-inflammatory disorders in 4, complement deficiencies in 36, and phenocopies of PID in none. From the HIRA reimbursement data, a total of 1,162 outpatients and 306 inpatients were treated for 8,166 and 6,149 days, respectively. In addition, reimbursement was requested for 8,200 outpatient and 1,090 inpatient cases and $1,924,000 and $4,715,000 were reimbursed in 2017, respectively. This study systematically reviewed published studies on PID and analyzed the national open data system of the HIRA to estimate the disease burden of PID, for the first time in Korea.

PMID: 32683811 [PubMed – as supplied by publisher]

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Pathogenesis of immune thrombocytopenia in common variable immunodeficiency.

Autoimmun Rev. 2020 Jul 16;:102616

Authors: Tinazzi E, Osti N, Beri R, Argentino G, Veneri D, Dima F, Bason C, Jadav G, Dolcino M, Puccetti A, Lunardi C

Abstract
Immune Thrombocitopenic Purpura (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction and variable reduced platelet production. Besides antibody-mediated platelet destruction, new pathogenic mechanisms have been reported to be involved in reducing platelet count. Among these, desialylation is one of the most recent and innovative mechanisms that has been found to be implied, at least in part, in non-antibody mediated platelet clearance. Common Variable Immunodeficiency (CVID) is the most common Primary Immunodeficiency seen in clinical practice. About 25-30% of CVID patients are affected by autoimmune manifestation, among which ITP is the most common. Little is know about pathophysiological mechanisms that lead to ITP in CVID. Given the poor antibody production typical of CVID patients, we aimed at verifying whether platelet desialylation could be responsible for CVID associated thrombocytopenia. According to our results, we may suggest that in CVID patients, ITP is due to a decreased bone marrow platelets production, rather than an increased peripheral platelet destruction, which is more common in patients with primary ITP. An increased platelet desialylation doesn’t appear to be implicated in the thrombocytopenia secondary to CVID, while it is implicated in the pathogenesis of primary ITP. Nevertheless an intriguing aspect has emerged from this study: regardless the presence of thrombocytopenia, the majority of CVID patients present a double platelet population as far as desialylation concerns, whilst no one of the healthy donors and of the patients with primary ITP shows a similar characteristic.

PMID: 32682985 [PubMed – as supplied by publisher]

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Clinical, Immunological and Genetic findings in Patients with UNC13D Deficiency (FHL3): a Systematic Review.

Pediatr Allergy Immunol. 2020 Jul 17;:

Authors: Amirifar P, Ranjouri MR, Abolhassani H, Moeini Shad T, Almasi-Hashiani A, Azizi G, Moamer S, Aghamohammadi A, Yazdani R

Abstract
BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive immune disorder that is caused by mutations in 6 different genes related to the formation and function of secretory lysosomes within cytotoxic T lymphocytes and natural killer (NK) cells. Thus defect in these genes are associated with the accumulation of antigens due to defective cytotoxic function. FHL type3 (FHL3) accounts for nearly 30-40% of FHL, and its underlying reason is mutation in UNC13D gene which encodes Munc13-4 protein.
METHODS: For the first time, we aimed to systematically review clinical features, immunologic data and genetic findings of patients with FHL3. We conducted electronic searches for English-language articles in PubMed, Web of Science, Embase, and Scopus databases to collect comprehensive records related to patients with UNC13D mutations.
RESULTS: A total of 279 abstracts were initially reviewed for inclusion. Among them, 57 articles corresponding to 322 individual FHL3 patients fulfilled our selection criteria. Finally, 73 and 249 patients were considered as a severe and mild feature groups, respectively. Our results confirmed that fever, hepatosplenomegaly and hemophagocytosis are common clinical features in the disease. Moreover, reduced fibrinogen, and NK cell activity as well as increased ferritin, and triglycerides are important markers for early diagnosis of the FHL3 disease. Investigation of genotype showed that the most prevalent type and zygosity of UNC13D are splice-site errors and compound heterozygous, respectively.
CONCLUSION: FHL3 patients have a wide range of clinical manifestations, which makes it difficult to diagnose. Therefore, it seems that the sequencing of the entire UNC13D gene (coding and non-coding regions) is the most appropriate way to accurate diagnosis of FHL3 patients.

PMID: 32679608 [PubMed – as supplied by publisher]

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Meta-analysis of hematopoietic stem cell transplantation in major histocompatibility complex class II deficiency.

Pediatr Transplant. 2020 Jul 17;:e13774

Authors: Castano-Jaramillo LM, Bareño-Silva J, Tobon S, Escobar-Gonzalez AF

Abstract
Major histocompatibility complex class II deficiency is a rare case of PID. Specific recommendations for hematopoietic stem cell transplant, the only curative treatment option, are still lacking. This meta-analysis aims to identify the factors associated with better prognosis in these patients. Thirteen articles reporting 63 patients with major histocompatibility complex class II deficiency that underwent hematopoietic stem cell transplant were included. The median age for hematopoietic stem cell transplant was 18 months. The most common source of transplant was bone marrow, with alternative sources as umbilical cord blood emerging during recent years. The highest proportion of engraftment was seen with umbilical cord. Engraftment was higher in patients with matched donors, with better overall survival in patients with reduced-intensity conditioning. Graft-vs-host disease developed in 65% of the patients, with grades I-II being the most frequently encountered. There was a higher mortality in patients with myeloablative conditioning and no engraftment. There was an inverse correlation between survival and stage of graft-vs-host disease. The main cause of mortality was infectious disease, mostly secondary to viral infections. Ideally, matched grafts should be used, and reduced-intensity conditioning should be considered to reduce early post-transplant complications. GVHD and viral prophylaxis are fundamental.

PMID: 32678504 [PubMed – as supplied by publisher]

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Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort.

Nature. 2020 Jul 17;:

Authors: Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F, Primary Immunodeficiency Consortium for the NIHR Bioresource, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, Smith KGC

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32678341 [PubMed – as supplied by publisher]

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Assessment of weight and height of patients with primary immunodeficiency disorders and group of children with recurrent respiratory tract infections.

BMC Immunol. 2020 Jul 16;21(1):42

Authors: Pieniawska-Śmiech K, Bar K, Babicki M, Śmiech K, Lewandowicz-Uszyńska A

Abstract
BACKGROUND: Primary immunodeficiences (PIDs) are a group of chronic, serious disorders in which the immune response is insufficient. In consequence, it leads to an increased susceptibility to infections. Up to date, there are about 350 different disorders classified in that group. There are also patients suffering from recurrent respiratory tract infections (RRTI), however that group doesn’t present any abnormalities in terms of conducted immunological tests. Many factors, including medical, can have an impact on physical development of a child. Data such as birth weight and length, also weight, height, BMI during admission to the hospital were collected from 195 patients’ medical histories from their hospitalization at Clinical Immunology and Paediatrics Ward of J. Gromkowski Hospital in Wrocław. Investigated groups included patients with PIDs, RRTI and a control group of healthy children. Our purpose was to evaluate the physical growth of children with PID and children with RRTI by assessment of their height and weight. All of parameters were evaluated using centile charts, suitable best for the Polish population.
RESULTS: The lowest mean birth weight and height was found among the PIDs patients group. Children with PIDs during hospitalization had statistically relevant lower mean weight than the control group and almost 18% of them had their height situated below 3rd percentile. The statistically relevant differences have been found between them and RRTI group in terms of weight, height and nutritional status. The statistically significant difference was detected between the nutritional status of PID and control group.
CONCLUSIONS: There is a higher percentage of PID patients with physical growth abnormalities in comparison to healthy children. Our findings indicate a need for further investigation of immune system irregularities and their influence on physical growth of children.

PMID: 32677887 [PubMed – as supplied by publisher]

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The challenges presented by haematopoietic stem cell transplantation in children with primary immunodeficiency.

Br Med Bull. 2020 Jul 15;:

Authors: Gennery AR

Abstract
INTRODUCTION OR BACKGROUND: For many primary immunodeficiencies (PIDs), haematopoietic stem cell transplantation (HSCT) offers treatment to cure disease. However, patients with PID present a unique set of challenges when considering HSCT.
SOURCES OF DATA: Review of recent literature.
AREAS OF AGREEMENT: The most significant recent impact on successful outcome is introduction of newborn screening programmes for diagnosis of severe combined immunodeficiency-wider adoption of screening in an increasing number of countries will see further improvements. Other PIDs have better outcomes when treated earlier, before development of co-morbidities-early referral for consideration of HSCT is important. Evolution of conditioning regimens is improving short- and long-term toxicities-targeted busulfan and low-toxicity myeloablative treosulfan regimens deliver good survival with reduced short-term toxicities.
AREAS OF CONTROVERSY: The most radical development, still in clinical trials, is the use of mono-antibody-based conditioning, which eliminates the requirement for chemotherapy and is likely to become much more important in HSCT for non-malignant disease in the future.
GROWING POINTS: Multidisciplinary working for optimum care is essential.
AREAS TIMELY FOR DEVELOPING RESEARCH: International collaborations are important to learn about rare presentations and complications, and to formulate the most effective and safe treatment strategies.

PMID: 32676650 [PubMed – as supplied by publisher]

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