LymphoSign Journal-The Journal of Inherited Immune Disorders最新文献

{"title":"Epstein–Barr virus infection in primary immunodeficiency","authors":"A. Ovadia, I. Dalal","doi":"10.14785/LYMPHOSIGN-2018-0011","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0011","url":null,"abstract":"Primary immunodeficiency (PID) is a group of genetic disorders which affects immune cell development, differentiation, and function. The affected individuals are highly susceptible to infection by a diverse array of pathogens. Epstein–Barr virus (EBV) infection is ubiquitous in humans and usually involves an asymptomatic or self-limiting clinical course. In rare cases, EBV can cause not only an acute infection but also a severe exaggerated immune response and lymphoproliferative disease. Furthermore, EBV infection in patients with PID can lead to immune dysregulation and increased risk of malignancies, in addition to the severe course of the acute infection. Recognition of the different genetic defects and their effect on immunological pathways provide us with fundamental insights into the pathophysiology of EBV infection and associated disease, and may lead to developing better targeted therapies in the future. Here, we review all of PIDs with an abnormal response to EBV disease. Statement of novelty: Here we provide a review of the current knowledge of all PIDs reported to be associated with abnormal response to EBV infection and associated disease, such as hemophagocytic lymphohistiocytosis.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48535783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene therapy for PNP deficiency protocol","authors":"L. Vong","doi":"10.14785/LYMPHOSIGN-2018-0007","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0007","url":null,"abstract":"Purine nucleoside phosphorylase (PNP) is a key enzyme required for the degradation of purine nucleosides into uric acid or their salvage into nucleic acids. Patients who are deficient in PNP suffer from progressive T cell immunodeficiency, with increased susceptibility to infections, autoimmunity, and neurologic abnormalities. In the absence of successful treatment to restore immune function, these patients rarely survive to adulthood. Hematopoietic stem cell transplantation is the only known cure for PNP deficiency. Use of an HLA-matched donor is preferable as the outcome with alternative donors have been variable; however, this option is rarely available. Gene therapy represents a therapeutic option that bypasses the need for a donor, and thus associated complications. Although first generation γ-retroviral vectors have been successful in some immunodeficiencies, in others, evidence of insertional mutagenesis prompted a halt in their use. More recently, the introduction of safer lentiviral vectors holds promise in offering a viable option to treat immunodeficiency. Here, we present a clinical trial protocol utilizing self-inactivating lentiviral vectors to treat PNP deficiency. Patients will be evaluated up to 3 years post-transplantation to determine the safety of lentiviral-treated stem cell infusion, as well as the extent of immune reconstitution. Statement of novelty: This protocol describes the novel treatment of PNP deficiency using lentiviral-based gene therapy.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46641556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physician–patient shared decision making in the treatment of primary immunodeficiency: an interview-based survey of immunologists","authors":"Christopher C. Lamb","doi":"10.14785/LYMPHOSIGN-2018-0010","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0010","url":null,"abstract":"Background: Patient–physician shared decision making (SDM) can result in better care as well as reduced treatment costs. A better understanding of the factors predicting when physicians implement SDM during the treatment of primary immunodeficiency (PID) could provide insight for making recommendations to improve outcomes and reduce healthcare costs in PID and other long-term chronic conditions. Method: This study made use of grounded theory and was based on the interview responses of 15 immunologists in the United States. It focused on their decision making in the diagnosis and treatment of PID, how they interact with patients, and the circumstances under which they encourage SDM with patients. Results: All invited immunologists took part in the interviews and were included in the study. All but one had 10 or more years of experience in treating PID. The study found that SDM is bounded/limited by “nudging” bias, power balance considerations, and consideration of patient health literacy alignment. Immunologists also reported that they were mainly responsible for coordinating care and for allowing sufficient time for consultations. Conclusion: SDM occurs between the physician and patient throughout the treatment of PID. The study also shows the ways physicians influence SDM by guiding patients through the process. Statement of novelty: Little is known about the factors that influence SDM in the long-term management of chronic diseases. The present study investigated the extent to which immunologists experienced in the treatment of patients with PID include SDM in clinical practice. Findings such of these may be of use when formulating treatment guidelines and improving the effectiveness of long-term management of PID.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43852455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal defects and immunodeficiency syndrome with normal in vitro IgG production","authors":"Alexandra Langlois, Bahar Torabi, M. Dembele, M. Desjardins, R. Alizadehfar, Moshe Ben-Shohan, I. D. Bie, A. Sant’Anna, C. Mccusker, B. Mazer","doi":"10.14785/LYMPHOSIGN-2018-0008","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0008","url":null,"abstract":"Background: Gastrointestinal defects and immunodeficiency syndrome (GIDID) is a severe neonatal disorder usually fatal within the first months of life. We report a case presenting with intestinal atresia, combined immunodeficiency, and a novel association with hypothyroidism and cardiac malformations. The immune phenotype was remarkable for agammaglobulinemia, lymphopenia, and mildly decreased lymphocyte proliferation. We present here the unique phenotype as well as studies to determine if the agammaglobulinemia was due to an intrinsic B lymphocyte defect. Methods: Peripheral blood mononuclear cells from the patient and a healthy control were isolated by Ficoll-Hypaque centrifugation and stimulated with anti-CD40, IL-4 and IL-21 for 7 days. Total IgG production was measured by ELISA in the supernatant of the stimulated sample on day 7. Cells were stained for CD19, CD27, IgM, CD11b, CD11c, and CD14. Results: At day 7, supernatant from the patient stimulated cells contained levels of total IgG comparable to the control (755 ng/mL vs. 658 ng/mL, respectively). B cell maturation appeared impaired, as morphologically the patient sample demonstrated fewer B cell clones and cells with dendritic projections. Conclusions: Despite this typical severe clinical picture of GIDID with agammaglobulinemia, IgG production was detected under optimal stimulation for induction of plasma cells. This suggests that there may not be an inherent defect in class switching and antibody production in B cells in this disorder. It is possible that the in vivo physical or cytokine milieu may be defective for optimal B cell function. Further studies assessing the function of the immune cells as well as possible gastrointestinal loss of immunoglobulins are needed in this disease. Statement of novelty: Despite much improvement in understanding the effects of TTC7A mutations in GIDID, the root cause of hypogammaglobulinemia in these patients is still unclear. The work portrayed in this study furthers the current knowledge. It suggests that when appropriately stimulated in vitro, this patient’s B cells were capable of adequate immunoglobulin production. Moreover, to the best of our knowledge, this patient is the first with this genetic defect to be reported with hypothyroidism and cardiac malformations.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46909506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukocyte adhesion deficiency-I caused by a novel mutation in ITGB2 presenting with pyoderma gangrenosum","authors":"A. Haynes, Andrew W O’Keefe, P. Dancey, K. Ohson, L. Turner, M. Chard","doi":"10.14785/LYMPHOSIGN-2018-0006","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0006","url":null,"abstract":"Background: Leukocyte adhesion deficiency (LAD) syndromes are primary immunodeficiency disorders caused by defects in adhesion molecules on leukocytes resulting in impaired migration into tissues. Common cutaneous manifestations of LAD include bacterial infections, omphalitis with delayed separation of the umbilical cord, impaired pus formation and poor wound healing. LAD is associated with significant morbidity and mortality, making early diagnosis and management integral in the care of these patients. Methods: Molecular testing and flow cytometry for expression of CD18 were performed on 2 siblings presenting with cutaneous lesions including pyoderma gangrenosum (PG). Results: We describe 2 siblings with a novel homozygous mutation in ITGB2 (c.2070del, p.Asp690Glufs*25) resulting in an atypical presentation of LAD-I with PG. Conclusion: LAD should be considered in patients presenting with unexplained PG, even in the absence of significant infections or umbilical cord complications. Statement of novelty: To the best of our knowledge, we describe a novel homozygous mutation in ITGB2 (c.2070del, p.Asp690Glufs*25) resulting in LAD-I. Patients with LAD-I may present with unexplained PG and may lack classic symptoms including umbilical cord complications.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49104319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an ambulatory infusion protocol for Abatacept","authors":"Karen Queffelec, Michelle Anderson, H. Convery, B. Reid","doi":"10.14785/LYMPHOSIGN-2018-0005","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0005","url":null,"abstract":"The identification of the genetic causes of Common Variable Immune Deficiency (CVID) has led to recognition of the need for biological medications to treat the autoimmune manifestations that CVID patients with LRBA and CTLA4 deficiency experience. Immunologists have not traditionally used biological medications as treatment in CVID patients and may not be familiar with the use of them. We present the process and protocol as well as a nursing checklist used by the Division of Rheumatology for the use of Abatacept. Statement of novelty: The methodology used to develop the order set and nursing checklist may be applied to other biologic medications as they become available.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43041836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of induced pluripotent stem cells to investigate the effects of purine nucleoside phosphorylase deficiency on neuronal development","authors":"Michael Tsui, J. Biro, J. Chan, W. Min, E. Grunebaum","doi":"10.14785/LYMPHOSIGN-2018-0003","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0003","url":null,"abstract":"Background: Inherited defects in the function of the purine nucleoside phosphorylase (PNP) enzyme can cause severe T cell immune deficiency and early death from infection, autoimmunity, or malignancy. In addition, more than 50% of patients suffer diverse non-infectious neurological complications. However the cause for the neurological abnormalities are not known. Objectives: Differentiate induced pluripotent stem cells (iPSC) from PNP-deficient patients into neuronal cells to better understand the effects of impaired purine metabolism on neuronal development. Methods: Sendai virus was used to generate pluripotent stem cells from PNP-deficient and healthy control lymphoblastoid cells. Cells were differentiated into neuronal cells through the formation of embryoid bodies. Results: After demonstration of pluripotency, normal karyotype, and retention of the PNP deficiency state, iPSC were differentiated into neuronal cells. PNP-deficient neuronal cells had reduced soma and nuclei size in comparison to cells derived from healthy controls. Spontaneous apoptosis, determined by Caspase-3 expression, was increased in PNP-deficient cells. Conclusions: iPSC from PNP-deficient patients can be differentiated into neuronal cells, thereby providing an important tool to study the effects of impaired purine metabolism on neuronal development and potential treatments. Statement of novelty: We report here the first generation and use of neuronal cells derived from induced pluripotent stem cells to model human PNP deficiency, thereby providing an important tool for better understanding and management of this condition.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44887480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-reactive protein and other biomarkers—the sense and non-sense of using inflammation biomarkers for the diagnosis of severe bacterial infection","authors":"T. Niehues","doi":"10.14785/LYMPHOSIGN-2018-0001","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0001","url":null,"abstract":"Severe bacterial infection (SBI) poses a significant clinical problem as its mortality and morbidity is still unacceptably high. A systematic literature analysis was performed with an emphasis on recent meta analyses examining the specificity and sensitivity of conventional inflammation biomarkers (C-reactive protein, procalcitonin, interleukin-6, interleukin-8) for diagnosing SBI. Most inflammation biomarkers do not show high sensitivity and are of limited value regarding SBI detection. To the practicing clinician, the sole use of inflammation markers is not useful for differentiating between viral or bacterial origin of infection in an individual patient. Thus, only in combination with clinical biometric markers, taken from patient history and physical examination, is the analysis of inflammation biomarkers to some degree helpful in clinical practice. To date, their sensitivity and specificity have been best captured in the field of neonatology, where levels of interleukin-6 have been measured in combination with relevant perinatal factors. The indiscriminate use of inflammation biomarkers for the diagnosis of SBI may lead to over diagnosis. Novel technologies for pathogen detection and more precise measurement of the host-response using microarrays, allowing for simultaneous detection of multiple genes or proteins, promise to improve the value of laboratory biomarkers for the diagnosis of SBI. Statement of novelty: Presented here is an up-to-date systematic analysis of C-reactive protein and inflammation biomarkers with regard to their use in the diagnosis of SBI. I question whether a broad use of C-reactive protein is useful in patients presenting with infection. The results of the systematic analysis are put into context with recent concerns about over-diagnosing in medicine. This paper is adapted from a publication in the German journal Monatsschrift Kinderheilkunde.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43971881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic granulomatous disease due to different mutations in patients from the same consanguineous extended family","authors":"A. Broides, R. Gavrieli, J. Levy, R. Levy, N. Hadad, D. Roos, B. Wolach, A. Nahum","doi":"10.14785/LYMPHOSIGN-2018-0004","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0004","url":null,"abstract":"Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease. Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":"1 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41513110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}