Pub Date : 2019-05-22DOI: 10.14785/LYMPHOSIGN-2019-0005
L. Vong
This protocol is excerpted from recent clinical trials used to study the pharmacokinetics, safety, and tolerability of subcutaneously administered immunoglobulin (SCIG) in subjects with primary immunodeficiency. The primary objective is to determine the weekly dose of SCIG product that produces a steady-state area under the concentration-time curve of total immunoglobulin G level that is non-inferior to that of regularly administered intravenous immunoglobulin (IVIG). We include details of the target population, eligibility criteria, treatment phases, key assessments and procedures, and study analyses. Given that IVIG may be problematic in patients with poor venous access or those who develop systemic adverse effects, among others, the development of SCIG for use in the home setting provides an alternative treatment technique for adults and children with primary immunodeficiency. Statement of novelty: This protocol describes the main topics found in prospective clinical studies evaluating the safety and pharmacokinetics of SCIG in subjects with primary immunodeficiency.
{"title":"A clinical trial protocol to evaluate the safety and pharmacokinetics of subcutaneously administered immunoglobulin in patients with primary immunodeficiency","authors":"L. Vong","doi":"10.14785/LYMPHOSIGN-2019-0005","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2019-0005","url":null,"abstract":"This protocol is excerpted from recent clinical trials used to study the pharmacokinetics, safety, and tolerability of subcutaneously administered immunoglobulin (SCIG) in subjects with primary immunodeficiency. The primary objective is to determine the weekly dose of SCIG product that produces a steady-state area under the concentration-time curve of total immunoglobulin G level that is non-inferior to that of regularly administered intravenous immunoglobulin (IVIG). We include details of the target population, eligibility criteria, treatment phases, key assessments and procedures, and study analyses. Given that IVIG may be problematic in patients with poor venous access or those who develop systemic adverse effects, among others, the development of SCIG for use in the home setting provides an alternative treatment technique for adults and children with primary immunodeficiency. Statement of novelty: This protocol describes the main topics found in prospective clinical studies evaluating the safety and pharmacokinetics of SCIG in subjects with primary immunodeficiency.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43443380","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}
Pub Date : 2019-04-24DOI: 10.14785/LYMPHOSIGN-2018-0016
Amarilla B. Mandola, Asako Nozawa, T. Eiwegger
Histamine is a bioactive amine which is considered a key player in the allergic response. Thus, histamine receptor blockers (antihistamines) play an important role in the treatment of a number atopic diseases such as allergic rhinitis, conjunctivitis, and acute and chronic forms of urticaria. Histamine is produced by immune cells but also by bacteria in the gut. Beyond its role in the acute allergic response, histamine exerts numerous effects by binding to its 4 pleiotropic G-protein coupled histamine receptors. Here, we describe the roles of these histamine receptors and antihistamines in the human system, clinical applications, side effects, and novel concepts for the usage of antihistamines with different specificity based on guidelines and recommendations. Statement of novelty: This review provides an overview of histamine receptors and links it to clinical relevance of antagonizing their action in clinical routine.
{"title":"Histamine, histamine receptors, and anti-histamines in the context of allergic responses","authors":"Amarilla B. Mandola, Asako Nozawa, T. Eiwegger","doi":"10.14785/LYMPHOSIGN-2018-0016","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0016","url":null,"abstract":"Histamine is a bioactive amine which is considered a key player in the allergic response. Thus, histamine receptor blockers (antihistamines) play an important role in the treatment of a number atopic diseases such as allergic rhinitis, conjunctivitis, and acute and chronic forms of urticaria. Histamine is produced by immune cells but also by bacteria in the gut. Beyond its role in the acute allergic response, histamine exerts numerous effects by binding to its 4 pleiotropic G-protein coupled histamine receptors. Here, we describe the roles of these histamine receptors and antihistamines in the human system, clinical applications, side effects, and novel concepts for the usage of antihistamines with different specificity based on guidelines and recommendations. Statement of novelty: This review provides an overview of histamine receptors and links it to clinical relevance of antagonizing their action in clinical routine.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44774951","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}
Pub Date : 2019-02-25DOI: 10.14785/LYMPHOSIGN-2019-0002
Mohammad Alsalamah, L. Vong, Lorand Cimpean, H. Dadi
Introduction: The evaluation of lymphocyte proliferation responses is a critical component of the clinical work up for patients with suspected immunodeficiencies. Those with severe combined immunodeficiency (SCID) have consistently low to absent responses (stimulation index, SI) to the mitogen phytohemagglutinin (PHA). However, patients with combined immunodeficiency (CID) have more varied proliferative responses, and are open to a wide range of interpretations. Aims: To establish lymphocyte proliferation response reference ranges for patients with T cell defects, especially those with CID as well as healthy controls. Methods: Data was collected retrospectively from charts of patients with a diagnosis of SCID (n = 39), CID (n = 52), or from healthy controls (n = 440). Reference percentiles were calculated using the 95% of the distribution of the test results. Results: The reference ranges for the control group ranged from 134 to 2220.5, whereas those with CID were distributed between 0.81 and 169.1. Patients with typical SCID had profound low proliferative responses, with SI <5. Conclusion: Our results highlight the variability of lymphocyte proliferation responses to PHA in patients with CID as well as healthy controls. These reference ranges will assist with the critical interpretation of assay results, particularly when values fall on the extreme end of the range. Statement of novelty: We provide reference ranges for lymphocyte proliferation responses to PHA from patients with CID and healthy controls.
{"title":"Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction","authors":"Mohammad Alsalamah, L. Vong, Lorand Cimpean, H. Dadi","doi":"10.14785/LYMPHOSIGN-2019-0002","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2019-0002","url":null,"abstract":"Introduction: The evaluation of lymphocyte proliferation responses is a critical component of the clinical work up for patients with suspected immunodeficiencies. Those with severe combined immunodeficiency (SCID) have consistently low to absent responses (stimulation index, SI) to the mitogen phytohemagglutinin (PHA). However, patients with combined immunodeficiency (CID) have more varied proliferative responses, and are open to a wide range of interpretations. Aims: To establish lymphocyte proliferation response reference ranges for patients with T cell defects, especially those with CID as well as healthy controls. Methods: Data was collected retrospectively from charts of patients with a diagnosis of SCID (n = 39), CID (n = 52), or from healthy controls (n = 440). Reference percentiles were calculated using the 95% of the distribution of the test results. Results: The reference ranges for the control group ranged from 134 to 2220.5, whereas those with CID were distributed between 0.81 and 169.1. Patients with typical SCID had profound low proliferative responses, with SI <5. Conclusion: Our results highlight the variability of lymphocyte proliferation responses to PHA in patients with CID as well as healthy controls. These reference ranges will assist with the critical interpretation of assay results, particularly when values fall on the extreme end of the range. Statement of novelty: We provide reference ranges for lymphocyte proliferation responses to PHA from patients with CID and healthy controls.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41878650","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}
Pub Date : 2019-02-25DOI: 10.14785/LYMPHOSIGN-2019-0003
S. Betschel, R. Brager, A. Haynes, T. Issekutz, V. Kim, B. Mazer, C. Mccusker, C. Roifman, Tamar S. Rubin, G. Sussman, S. Turvey, S. Waserman
Immunoglobulin replacement therapy is a mainstay in the treatment of immune deficiencies characterized by antibody failure. Whether the cause is primary or secondary, affected patients frequently present with a history recurrent and complicated infections of the upper and (or) lower respiratory tract. Such replacement therapy has been available since the 1980s, although treatment modalities have since been refined to provide improved protection against infections resulting in reduced morbidity and mortality. Here, we describe an algorithm for diagnosing patients with suspected primary or secondary immunodeficiency, including assessment of clinical, laboratory, and genetic information, when considering initiating immunoglobulin replacement. The increasing availability of molecular genetic techniques will likely result in decreased diagnostic delay for these patients. Statement of novelty: We describe here an algorithm for diagnosing patients with immunodeficiency requiring immunoglobulin replacement therapy.
{"title":"Report of the National Immunoglobulin Replacement Expert Committee: algorithm for diagnosis of immunodeficiency requiring antibody replacement therapy","authors":"S. Betschel, R. Brager, A. Haynes, T. Issekutz, V. Kim, B. Mazer, C. Mccusker, C. Roifman, Tamar S. Rubin, G. Sussman, S. Turvey, S. Waserman","doi":"10.14785/LYMPHOSIGN-2019-0003","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2019-0003","url":null,"abstract":"Immunoglobulin replacement therapy is a mainstay in the treatment of immune deficiencies characterized by antibody failure. Whether the cause is primary or secondary, affected patients frequently present with a history recurrent and complicated infections of the upper and (or) lower respiratory tract. Such replacement therapy has been available since the 1980s, although treatment modalities have since been refined to provide improved protection against infections resulting in reduced morbidity and mortality. Here, we describe an algorithm for diagnosing patients with suspected primary or secondary immunodeficiency, including assessment of clinical, laboratory, and genetic information, when considering initiating immunoglobulin replacement. The increasing availability of molecular genetic techniques will likely result in decreased diagnostic delay for these patients. Statement of novelty: We describe here an algorithm for diagnosing patients with immunodeficiency requiring immunoglobulin replacement therapy.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45614440","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}
Pub Date : 2019-02-22DOI: 10.14785/LYMPHOSIGN-2019-0001
Y. Schejter, Amarilla B. Mandola, B. Reid
Introduction: Coronin 1A belongs to a large family of actin regulatory proteins with a role in T cell homeostasis. A role for coronin 1A was also observed in macrophages, NK, and neuronal cells. To date, coronin 1A deficiency has been described in relatively few patients with combined immunodeficiency. Aim: We studied here the molecular and genetic basis of immunodeficiency detected by newborn screening for severe combined immunodeficiency. Methods: Patient data was collected in accordance with REB approved protocols. Immune work up, including T and B cell proliferative responses and serum concentrations of immunoglobulins, was performed. Next generation sequencing techniques and cellular analyses were also utilized. Results: The patient presented with T cell lymphopenia, reduction in CD4+CD45Ra+ cells and hypogammaglobulinemia. Uniquely, she also had persistent severe neutropenia. Whole exome sequencing and Sanger confirmation revealed a novel homozygous mutation in coronin 1A. Conclusion: Coronin 1A deficiency can be detected after birth by T cell receptor excision circle-based newborn screening. Statement of novelty: We report here a patient with a novel mutation in coronin 1A, identified during newborn screening with low T cell receptor excision circle levels and neutropenia, which is a unique finding in this condition.
{"title":"Coronin 1A deficiency identified by newborn screening for severe combined immunodeficiency","authors":"Y. Schejter, Amarilla B. Mandola, B. Reid","doi":"10.14785/LYMPHOSIGN-2019-0001","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2019-0001","url":null,"abstract":"Introduction: Coronin 1A belongs to a large family of actin regulatory proteins with a role in T cell homeostasis. A role for coronin 1A was also observed in macrophages, NK, and neuronal cells. To date, coronin 1A deficiency has been described in relatively few patients with combined immunodeficiency. Aim: We studied here the molecular and genetic basis of immunodeficiency detected by newborn screening for severe combined immunodeficiency. Methods: Patient data was collected in accordance with REB approved protocols. Immune work up, including T and B cell proliferative responses and serum concentrations of immunoglobulins, was performed. Next generation sequencing techniques and cellular analyses were also utilized. Results: The patient presented with T cell lymphopenia, reduction in CD4+CD45Ra+ cells and hypogammaglobulinemia. Uniquely, she also had persistent severe neutropenia. Whole exome sequencing and Sanger confirmation revealed a novel homozygous mutation in coronin 1A. Conclusion: Coronin 1A deficiency can be detected after birth by T cell receptor excision circle-based newborn screening. Statement of novelty: We report here a patient with a novel mutation in coronin 1A, identified during newborn screening with low T cell receptor excision circle levels and neutropenia, which is a unique finding in this condition.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":"1 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41475822","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}
Pub Date : 2019-01-28DOI: 10.14785/LYMPHOSIGN-2018-0012
R. Seger
Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and to resolve inflammation. The last few years have witnessed major advances in pathogenesis and clinical management of the disease: Better understanding of 3 physiologic anti-inflammatory functions of NADPH oxidase-derived reactive oxygen species: Promotion of the clearance of dying host cells, suppression of inflammasomes, and regulation of type I interferon signalling. This insight is opening new avenues for targeted drug interventions. Advances in reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell transplantation (HSCT) make it a promising and safe procedure even for fragile patients with ongoing severe infection or hyperinflammation. Encouraging early data of a multicenter trial of gene-replacement therapy using a self-inactivated lentiviral vector. Combining targeted anti-infectious/anti-inflammatory measures and considering extended indications for curative HSCT are key to improving patient outcome further. Gene therapy will likely become a viable option for disease correction, but long-term assessment is not yet possible. Statement of novelty: We discuss important advances in pathogenesis and treatment of CGD that will change our approach to clinical management.
{"title":"Chronic granulomatous disease 2018: advances in pathophysiology and clinical management","authors":"R. Seger","doi":"10.14785/LYMPHOSIGN-2018-0012","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0012","url":null,"abstract":"Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and to resolve inflammation. The last few years have witnessed major advances in pathogenesis and clinical management of the disease: Better understanding of 3 physiologic anti-inflammatory functions of NADPH oxidase-derived reactive oxygen species: Promotion of the clearance of dying host cells, suppression of inflammasomes, and regulation of type I interferon signalling. This insight is opening new avenues for targeted drug interventions. Advances in reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell transplantation (HSCT) make it a promising and safe procedure even for fragile patients with ongoing severe infection or hyperinflammation. Encouraging early data of a multicenter trial of gene-replacement therapy using a self-inactivated lentiviral vector. Combining targeted anti-infectious/anti-inflammatory measures and considering extended indications for curative HSCT are key to improving patient outcome further. Gene therapy will likely become a viable option for disease correction, but long-term assessment is not yet possible. Statement of novelty: We discuss important advances in pathogenesis and treatment of CGD that will change our approach to clinical management.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":"1 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2019-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66653326","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}
Pub Date : 2018-12-01DOI: 10.14785/LYMPHOSIGN-2018-0009
C. Weisser, D. Bulman, Kayla Flamenbaum, Maian Roifman
Background: The protein encoded by interleukin-2 receptor common gamma chain (IL2RG) is an important signaling component of many interleukin receptors, including those of interleukin-2, -4, -7, and -21, known as the common gamma chain. Mutations in the gene encoding the common gamma chain of the interleukin-2 receptor cause X-linked severe combined immunodeficiency (SCID). In this report, we present an unknown genetic defect of a patient diagnosed with SCID whose genetic analysis was performed 2 decades later. Methods: Whole genome sequencing and Sanger confirmation were used to identify a novel frameshift mutation in IL2RG. Massively parallel sequencing of genes associated with SCID were performed on the patient’s mother and sister. Results: Next generation sequencing techniques identified a heterozygous frame-shift deletion in the gene encoding the common gamma chain of IL2RG in our patient. The patient’s mother had a low level mosaicism for the same deletion. The sister had no detectable deletion. Conclusion: We have identified a novel mutation in IL2RG resulting in an X-linked SCID phenotype. The genetic analysis of the patient’s mother revealed a mosaicism which was not passed on to his sister. The importance of genetic analysis in family members and SCID patients with an unknown genetic defect should be emphasized for family planning and subsequent genetic counseling. Statement of novelty: Genetic testing is an extremely important component in evaluating severe combined immunodeficiency as it impacts treatment course and prognosis, and allows for genetic analysis and counselling of family members.
{"title":"Interleukin-2 receptor common gamma chain (IL2RG) defects present a diagnostic challenge","authors":"C. Weisser, D. Bulman, Kayla Flamenbaum, Maian Roifman","doi":"10.14785/LYMPHOSIGN-2018-0009","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0009","url":null,"abstract":"Background: The protein encoded by interleukin-2 receptor common gamma chain (IL2RG) is an important signaling component of many interleukin receptors, including those of interleukin-2, -4, -7, and -21, known as the common gamma chain. Mutations in the gene encoding the common gamma chain of the interleukin-2 receptor cause X-linked severe combined immunodeficiency (SCID). In this report, we present an unknown genetic defect of a patient diagnosed with SCID whose genetic analysis was performed 2 decades later. Methods: Whole genome sequencing and Sanger confirmation were used to identify a novel frameshift mutation in IL2RG. Massively parallel sequencing of genes associated with SCID were performed on the patient’s mother and sister. Results: Next generation sequencing techniques identified a heterozygous frame-shift deletion in the gene encoding the common gamma chain of IL2RG in our patient. The patient’s mother had a low level mosaicism for the same deletion. The sister had no detectable deletion. Conclusion: We have identified a novel mutation in IL2RG resulting in an X-linked SCID phenotype. The genetic analysis of the patient’s mother revealed a mosaicism which was not passed on to his sister. The importance of genetic analysis in family members and SCID patients with an unknown genetic defect should be emphasized for family planning and subsequent genetic counseling. Statement of novelty: Genetic testing is an extremely important component in evaluating severe combined immunodeficiency as it impacts treatment course and prognosis, and allows for genetic analysis and counselling of family members.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45098064","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}
Pub Date : 2018-12-01DOI: 10.14785/lymphosign-2018-0014
{"title":"Abstracts from the Immunodeficiency Canada—6th SCID Symposium, Halifax, NS, 13 September 2018","authors":"","doi":"10.14785/lymphosign-2018-0014","DOIUrl":"https://doi.org/10.14785/lymphosign-2018-0014","url":null,"abstract":"","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42322756","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}
Pub Date : 2018-12-01DOI: 10.14785/LYMPHOSIGN-2018-0015
J. Hsieh, Amarilla B. Mandola, S. Betschel
Introduction: Major histocompatibility (MHC) class II deficiency is a rare autosomal recessive primary immunodeficiency with fewer than 200 patients reported worldwide. Patients usually present within their first year of life with severe and recurrent infections, failure to thrive, and chronic diarrhea. The disorder is caused by absent or reduced MHC class II expression on cell surfaces, leading to defective cellular and humoral immune responses. The disease is associated with a poor prognosis, with most patients dying in early childhood due to infectious complications. Aim: To report the clinical, immunological, and genetic features of an adult patient with MHC class II deficiency who did not undergo hematopoietic stem cell transplant (HSCT). We also explore proposed theories as to why some patients with MHC class II deficiency survive to adulthood, beyond the typical life expectancy. Results: We present a 23-year-old gentleman who was diagnosed with MHC class II deficiency at the age of 6 months based on a near complete absence of Human Leukocyte Antigen - DR isotype on peripheral blood mononuclear cells and CD4+ lymphopenia. He is one of a few patients with the condition reported in the literature to have survived to adulthood despite not having undergone HSCT. Next generation sequencing revealed a novel homozygous mutation in the CIITA gene, 1 of 4 genes involved in the regulation of MHC class II transcription. Discussion: MHC class II deficiency is considered a single entity phenotypic condition where the main problem lies in reduced or absent MHC class II expression and results in downstream immunologic effects, including CD4+ lymphopenia and impaired antigen specific responses. However, phenotypic differences between patients are emerging as more cases are described in the literature. Our patient, now 23 years old, has survived significantly beyond life expectancy despite not having HSCT. Statement of novelty: We describe a case of an adult patient diagnosed with MHC class II deficiency due to a novel homozygous intronic splice site variant in the CIITA gene.
{"title":"A novel homozygous mutation in CIITA resulting in MHC Class II deficiency in an adult patient","authors":"J. Hsieh, Amarilla B. Mandola, S. Betschel","doi":"10.14785/LYMPHOSIGN-2018-0015","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0015","url":null,"abstract":"Introduction: Major histocompatibility (MHC) class II deficiency is a rare autosomal recessive primary immunodeficiency with fewer than 200 patients reported worldwide. Patients usually present within their first year of life with severe and recurrent infections, failure to thrive, and chronic diarrhea. The disorder is caused by absent or reduced MHC class II expression on cell surfaces, leading to defective cellular and humoral immune responses. The disease is associated with a poor prognosis, with most patients dying in early childhood due to infectious complications. Aim: To report the clinical, immunological, and genetic features of an adult patient with MHC class II deficiency who did not undergo hematopoietic stem cell transplant (HSCT). We also explore proposed theories as to why some patients with MHC class II deficiency survive to adulthood, beyond the typical life expectancy. Results: We present a 23-year-old gentleman who was diagnosed with MHC class II deficiency at the age of 6 months based on a near complete absence of Human Leukocyte Antigen - DR isotype on peripheral blood mononuclear cells and CD4+ lymphopenia. He is one of a few patients with the condition reported in the literature to have survived to adulthood despite not having undergone HSCT. Next generation sequencing revealed a novel homozygous mutation in the CIITA gene, 1 of 4 genes involved in the regulation of MHC class II transcription. Discussion: MHC class II deficiency is considered a single entity phenotypic condition where the main problem lies in reduced or absent MHC class II expression and results in downstream immunologic effects, including CD4+ lymphopenia and impaired antigen specific responses. However, phenotypic differences between patients are emerging as more cases are described in the literature. Our patient, now 23 years old, has survived significantly beyond life expectancy despite not having HSCT. Statement of novelty: We describe a case of an adult patient diagnosed with MHC class II deficiency due to a novel homozygous intronic splice site variant in the CIITA gene.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46167410","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}
Pub Date : 2018-11-20DOI: 10.14785/LYMPHOSIGN-2018-0013
S. Prasad, J. Lipszyc, S. Tarlo
Background: Cleaning and disinfecting agents are widely used in modern life, in homes, schools, public places, and workplaces as well as in recreational facilities such as swimming pools. Use has been for sanitizing purposes and to assist in reduction of infection as well as for deodorizing purposes. However, adverse respiratory effects have been associated with use of cleaning products ranging from effects in infancy and early childhood up to adults at home and work. Methods: This review summarizes recent published literature on the effects of cleaning agents used pre-natally, in childhood and adult life, at home, work, and in swimming pools. Results: Several studies have indicated that there is an increased risk of developing asthma among adults with frequent exposure to cleaning products at work and in the home. Potential mechanisms include sensitization and respiratory irritant effects. Exposure to irritant chlorine by-products from swimming pools have also been associated with respiratory effects and increased risk of asthma. Potential effects from maternal exposures to cleaning products on infants, and effects on early childhood atopy are less clear. Conclusions: Exposure to cleaning agents increases relative risks of asthma among workers, and adults using these agents in the home. Risks are also increased with exposure to chlorinated by-products from swimming pools, both in adults and children. Further studies are needed to understand the mechanisms of these associations.
{"title":"Update on effects of cleaning agents on allergy and asthma","authors":"S. Prasad, J. Lipszyc, S. Tarlo","doi":"10.14785/LYMPHOSIGN-2018-0013","DOIUrl":"https://doi.org/10.14785/LYMPHOSIGN-2018-0013","url":null,"abstract":"Background: Cleaning and disinfecting agents are widely used in modern life, in homes, schools, public places, and workplaces as well as in recreational facilities such as swimming pools. Use has been for sanitizing purposes and to assist in reduction of infection as well as for deodorizing purposes. However, adverse respiratory effects have been associated with use of cleaning products ranging from effects in infancy and early childhood up to adults at home and work. Methods: This review summarizes recent published literature on the effects of cleaning agents used pre-natally, in childhood and adult life, at home, work, and in swimming pools. Results: Several studies have indicated that there is an increased risk of developing asthma among adults with frequent exposure to cleaning products at work and in the home. Potential mechanisms include sensitization and respiratory irritant effects. Exposure to irritant chlorine by-products from swimming pools have also been associated with respiratory effects and increased risk of asthma. Potential effects from maternal exposures to cleaning products on infants, and effects on early childhood atopy are less clear. Conclusions: Exposure to cleaning agents increases relative risks of asthma among workers, and adults using these agents in the home. Risks are also increased with exposure to chlorinated by-products from swimming pools, both in adults and children. Further studies are needed to understand the mechanisms of these associations.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2018-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49283299","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}
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