Pub Date : 2024-09-18DOI: 10.2500/aap.2024.45.240046
John Anderson,Daniel Soteres,Raffi Tachdjian,Jennifer Mellor,Lucy Earl,Hannah Connolly,Kieran Wynne-Cattanach,Kellyn Moran,Krystal Sing,Bob G Schultz,Salome Juethner
BACKGROUNDHereditary angioedema (HAE) is a rare genetic disorder characterized by painful, debilitating, and potentiallyfatal swelling attacks. Lanadelumab is approved as long-term prophylaxis (LTP) in patients with HAE. However, realworld data on LTP use in patients with HAE are limited.OBJECTIVETo describe clinical characteristics, attack history, and quality of life (QoL) of patients with HAE type I/II whowere receiving lanadelumab or other LTPs.METHODSData were drawn from the Adelphi HAE Disease Specific Program, a cross-sectional survey of HAE physicians conducted in the United States from July to November 2021. Physician-reported disease characteristics, HAE attack frequency, and QoL were compared among patients receiving lanadelumab or other LTPs for at least 12 months.RESULTSPhysicians reported data for 144 patients, of whom 29 had received lanadelumab and 115 had received another prophylaxis for at least 12 months. The mean +/- standard deviation number of attacks in the previous 12 months was loweramong patients receiving lanadelumab than other LTPs (2.3 +/- 3.1 versus 3.4 +/- 2.8, respectively; p = 0.075). Although bothgroups had similar current disease activity and severity, more patients receiving lanadelumab versus other LTPs had high disease activity (51.7% versus 12.5%, respectively; p < 0.0001) and disease severity rated as severe (51.7% versus 16.1%, respectively; p = 0.0001) at diagnosis. Physicians reported that more patients who received lanadelumab had good or very good QoL(72.4%) than those receiving other LTPs (36.5%) (p = 0.003).CONCLUSIONAnalysis of these findings suggests lower attack frequency, lower symptomatic impact, and better QoL inpatients treated with lanadelumab than another prophylaxis in a real-world setting.
背景遗传性血管性水肿（HAE）是一种罕见的遗传性疾病，其特点是肿胀发作时疼痛难忍、使人衰弱并可能致命。拉那珠单抗被批准作为 HAE 患者的长期预防用药 (LTP)。目的描述接受拉那珠单抗或其他 LTPs 的 I/II 型 HAE 患者的临床特征、发作史和生活质量（QoL）。方法数据来自 Adelphi HAE 特定疾病项目，该项目是 2021 年 7 月至 11 月在美国对 HAE 医生进行的横断面调查。结果医生报告了144名患者的数据，其中29名患者接受了拉那珠单抗治疗，115名患者接受了至少12个月的其他预防治疗。接受拉那珠单抗治疗的患者在过去12个月中的平均+/-标准差发作次数低于接受其他LTP治疗的患者（分别为2.3 +/- 3.1对3.4 +/- 2.8；P = 0.075）。虽然两组患者目前的疾病活动度和严重程度相似，但接受拉那珠单抗治疗的患者比接受其他 LTP 治疗的患者在诊断时疾病活动度高（分别为 51.7% 对 12.5%；p < 0.0001），疾病严重程度被评为重度（分别为 51.7% 对 16.1%；p = 0.0001）。医生报告称，与接受其他 LTPs 治疗的患者（36.5%）相比，接受 lanadelumab 治疗的患者（72.4%）的 QoL 更好或非常好（p = 0.003）。
{"title":"Real-world outcomes in patients with hereditary angioedema prescribed lanadelumab versus other prophylaxis.","authors":"John Anderson,Daniel Soteres,Raffi Tachdjian,Jennifer Mellor,Lucy Earl,Hannah Connolly,Kieran Wynne-Cattanach,Kellyn Moran,Krystal Sing,Bob G Schultz,Salome Juethner","doi":"10.2500/aap.2024.45.240046","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240046","url":null,"abstract":"BACKGROUNDHereditary angioedema (HAE) is a rare genetic disorder characterized by painful, debilitating, and potentiallyfatal swelling attacks. Lanadelumab is approved as long-term prophylaxis (LTP) in patients with HAE. However, realworld data on LTP use in patients with HAE are limited.OBJECTIVETo describe clinical characteristics, attack history, and quality of life (QoL) of patients with HAE type I/II whowere receiving lanadelumab or other LTPs.METHODSData were drawn from the Adelphi HAE Disease Specific Program, a cross-sectional survey of HAE physicians conducted in the United States from July to November 2021. Physician-reported disease characteristics, HAE attack frequency, and QoL were compared among patients receiving lanadelumab or other LTPs for at least 12 months.RESULTSPhysicians reported data for 144 patients, of whom 29 had received lanadelumab and 115 had received another prophylaxis for at least 12 months. The mean +/- standard deviation number of attacks in the previous 12 months was loweramong patients receiving lanadelumab than other LTPs (2.3 +/- 3.1 versus 3.4 +/- 2.8, respectively; p = 0.075). Although bothgroups had similar current disease activity and severity, more patients receiving lanadelumab versus other LTPs had high disease activity (51.7% versus 12.5%, respectively; p < 0.0001) and disease severity rated as severe (51.7% versus 16.1%, respectively; p = 0.0001) at diagnosis. Physicians reported that more patients who received lanadelumab had good or very good QoL(72.4%) than those receiving other LTPs (36.5%) (p = 0.003).CONCLUSIONAnalysis of these findings suggests lower attack frequency, lower symptomatic impact, and better QoL inpatients treated with lanadelumab than another prophylaxis in a real-world setting.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269570","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 : 2024-09-13DOI: 10.2500/aap.2024.45.240033
Martyn Paddick,Kim Clark,Eric Wolford,John More
BACKGROUNDInadequate production of immunoglobulin G (IgG) antibodies renders patients with primary immunodeficiencysusceptible to infection by numerous pathogens, some of which can lead to severe asthma exacerbation and possible death. These patients who are immunocompromised are often reliant on intravenous immunoglobulin (IVIG) therapies, which provide passive antibodies against various respiratory pathogens, including measles virus and encapsulated bacteria.OBJECTIVEWe conducted a subanalysis of data from a multicenter, multinational, phase III, open-label bioequivalencestudy to compare protective concentrations of IgG antibodies provided by a 5% and a 10% IVIG product in patients with primaryimmunodeficiency.METHODSPatients on stable 21- or 28-day regimens of previous IVIG products were assigned to receive study treatment (adults: 5% IVIG and 10% IVIG; children: 10% IVIG) at doses of 300-800 mg/kg per infusion. Trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, and IgG against Haemophilus influenzae type b and Streptococcus pneumoniae serotypes were evaluated.RESULTSA total of 48 patients (33 adults ages 16-55 years; 15 children ages 2-15 years) were enrolled and received treatment.No statistically significant differences in trough concentrations of total IgG, IgG subclasses, measles neutralizing antibodies, or IgG directed at encapsulated bacteria were observed between the 5% and 10% formulations in analyses by age (adult or pediatric) or infusion schedule (every 21 or 28 days). All evaluated patients had trough IgG concentrations above accepted thresholds for protection against disease.CONCLUSIONThese findings support the conclusion that, at dose levels and infusion schedules prescribed in clinical practice,this 5% and 10% IVIG product provided consistent, predictable, and bioequivalent IgG concentrations for adult and pediatricpatients with primary immunodeficiency disease. Both formulations delivered trough antibody concentrations of total IgG, measles- neutralizing antibodies, and antibodies against encapsulated bacteria that are above thresholds accepted as protective.
{"title":"Protective antibody concentrations in primary immunodeficiency following infusion with 5% or 10% intravenous immunoglobulin.","authors":"Martyn Paddick,Kim Clark,Eric Wolford,John More","doi":"10.2500/aap.2024.45.240033","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240033","url":null,"abstract":"BACKGROUNDInadequate production of immunoglobulin G (IgG) antibodies renders patients with primary immunodeficiencysusceptible to infection by numerous pathogens, some of which can lead to severe asthma exacerbation and possible death. These patients who are immunocompromised are often reliant on intravenous immunoglobulin (IVIG) therapies, which provide passive antibodies against various respiratory pathogens, including measles virus and encapsulated bacteria.OBJECTIVEWe conducted a subanalysis of data from a multicenter, multinational, phase III, open-label bioequivalencestudy to compare protective concentrations of IgG antibodies provided by a 5% and a 10% IVIG product in patients with primaryimmunodeficiency.METHODSPatients on stable 21- or 28-day regimens of previous IVIG products were assigned to receive study treatment (adults: 5% IVIG and 10% IVIG; children: 10% IVIG) at doses of 300-800 mg/kg per infusion. Trough concentrations of total IgG, IgG subclasses, measles-neutralizing antibodies, and IgG against Haemophilus influenzae type b and Streptococcus pneumoniae serotypes were evaluated.RESULTSA total of 48 patients (33 adults ages 16-55 years; 15 children ages 2-15 years) were enrolled and received treatment.No statistically significant differences in trough concentrations of total IgG, IgG subclasses, measles neutralizing antibodies, or IgG directed at encapsulated bacteria were observed between the 5% and 10% formulations in analyses by age (adult or pediatric) or infusion schedule (every 21 or 28 days). All evaluated patients had trough IgG concentrations above accepted thresholds for protection against disease.CONCLUSIONThese findings support the conclusion that, at dose levels and infusion schedules prescribed in clinical practice,this 5% and 10% IVIG product provided consistent, predictable, and bioequivalent IgG concentrations for adult and pediatricpatients with primary immunodeficiency disease. Both formulations delivered trough antibody concentrations of total IgG, measles- neutralizing antibodies, and antibodies against encapsulated bacteria that are above thresholds accepted as protective.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269580","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240051
Natchanun Klangkalya,Thomas A Fleisher,Sergio D Rosenzweig
Primary immunodeficiency diseases encompass a variety of genetic conditions characterized by a compromised immune system and typically results in increased susceptibility to infection. In fact, they also manifest as autoimmunity, autoinflammation, atopic diseases, and malignancy. Currently, the number of recognized monogenic primary immunodeficiency disorders is set at ∼500 different entities, owing to the exponential use of unbiased genetic testing for disease discovery. In addition, the prevalence of secondary immunodeficiency has also been on the rise due to the increased use of immunosuppressive drugs to treat diseases based on immune dysregulation, an increase in the number of individuals undergoing hematopoietic stem cell transplantation, and other chronic medical conditions, including autoimmunity. Although the clinical symptoms of immunodeficiency disorders are broad, an early diagnosis and tailored management strategies are essential to mitigate the risk of infections and prevent disease-associated morbidity. Generally, the medical history and physical examination can provide useful information that can help delineate the possibility of immune defects. In turn, this makes it feasible to select focused laboratory tests that identify immunodeficiency disorders based on the specific immune cells and their functions or products that are affected. Laboratory evaluation involves quantitative and functional classic testing (e.g., leukocyte counts, serum immunoglobulin levels, specific antibody titers in response to vaccines, and enumeration of lymphocyte subsets) as well as genetic testing (e.g., individual gene evaluation via Sanger sequencing or unbiased evaluation based on next-generation sequencing). However, in many cases, a diagnosis also requires additional advanced research techniques to validate genetic or other findings. This article updates clinicians about available laboratory tests for evaluating the immune system in patients with primary immunodeficiency disorders. It also provides a comprehensive list of testing options, organized based on different components of host defense.
{"title":"Diagnostic tests for primary immunodeficiency disorders: Classic and genetic testing.","authors":"Natchanun Klangkalya,Thomas A Fleisher,Sergio D Rosenzweig","doi":"10.2500/aap.2024.45.240051","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240051","url":null,"abstract":"Primary immunodeficiency diseases encompass a variety of genetic conditions characterized by a compromised immune system and typically results in increased susceptibility to infection. In fact, they also manifest as autoimmunity, autoinflammation, atopic diseases, and malignancy. Currently, the number of recognized monogenic primary immunodeficiency disorders is set at ∼500 different entities, owing to the exponential use of unbiased genetic testing for disease discovery. In addition, the prevalence of secondary immunodeficiency has also been on the rise due to the increased use of immunosuppressive drugs to treat diseases based on immune dysregulation, an increase in the number of individuals undergoing hematopoietic stem cell transplantation, and other chronic medical conditions, including autoimmunity. Although the clinical symptoms of immunodeficiency disorders are broad, an early diagnosis and tailored management strategies are essential to mitigate the risk of infections and prevent disease-associated morbidity. Generally, the medical history and physical examination can provide useful information that can help delineate the possibility of immune defects. In turn, this makes it feasible to select focused laboratory tests that identify immunodeficiency disorders based on the specific immune cells and their functions or products that are affected. Laboratory evaluation involves quantitative and functional classic testing (e.g., leukocyte counts, serum immunoglobulin levels, specific antibody titers in response to vaccines, and enumeration of lymphocyte subsets) as well as genetic testing (e.g., individual gene evaluation via Sanger sequencing or unbiased evaluation based on next-generation sequencing). However, in many cases, a diagnosis also requires additional advanced research techniques to validate genetic or other findings. This article updates clinicians about available laboratory tests for evaluating the immune system in patients with primary immunodeficiency disorders. It also provides a comprehensive list of testing options, organized based on different components of host defense.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269574","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240062
Joseph A Bellanti,Russell A Settipane
{"title":"Essentials of an immunodeficiency primer: A practical reference for the allergist/immunologist and the allergy-immunology fellow-in-training (FIT).","authors":"Joseph A Bellanti,Russell A Settipane","doi":"10.2500/aap.2024.45.240062","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240062","url":null,"abstract":"","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269572","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240055
Kamran Imam,Jenny Huang,Andrew A White
Background: Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. Methods: These isotype deficiencies have a variable presentation from asymptomatic to recurrent infections resistant to prophylactic antibiotics. Results: Atopic disorders and autoimmune diseases are common comorbidities. IgE deficiency has been associated with impaired vaccine response and an increased risk of malignancy, particularly in patients with no allergic comorbidities and those with non-common variable immunodeficiency (CVID) humoral immunodeficiency, IgM deficiency, IgG2 deficiency, and CD4 lymphopenia. Conclusion: Close monitoring for malignancy should be strongly considered for these patients who are at risk. Treatment is variable and may include antimicrobial therapies for illnesses and prophylactic antibiotics in select patients, and immunoglobulin replacement can be considered for patients with refractory, recurrent infections.
{"title":"Isotype deficiencies (IgG subclass and selective IgA, IgM, IgE deficiencies).","authors":"Kamran Imam,Jenny Huang,Andrew A White","doi":"10.2500/aap.2024.45.240055","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240055","url":null,"abstract":"Background: Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. Methods: These isotype deficiencies have a variable presentation from asymptomatic to recurrent infections resistant to prophylactic antibiotics. Results: Atopic disorders and autoimmune diseases are common comorbidities. IgE deficiency has been associated with impaired vaccine response and an increased risk of malignancy, particularly in patients with no allergic comorbidities and those with non-common variable immunodeficiency (CVID) humoral immunodeficiency, IgM deficiency, IgG2 deficiency, and CD4 lymphopenia. Conclusion: Close monitoring for malignancy should be strongly considered for these patients who are at risk. Treatment is variable and may include antimicrobial therapies for illnesses and prophylactic antibiotics in select patients, and immunoglobulin replacement can be considered for patients with refractory, recurrent infections.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269577","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240070
Cody S Nelson,Carolyn H Baloh
Primary immune regulatory disorders (PIRD) comprise a heterogeneous group of monogenic disorders that impact homeostatic control of inflammation and immune tolerance. Patients with a PIRD typically present to medical care with symptoms of autoimmunity or hyperinflammation as the dominant clinical feature, symptoms that include fever, rash, lymphadenopathy, organomegaly, arthritis, and colitis are commonplace. Notably, PIRDs are a distinct entity from primary immune deficiency disorders (PIDD), which are primarily defined by a qualitative or quantitative defect in immunity, which manifests as a susceptibility to recurrent infections. PIDDs and PIRDs can be challenging to differentiate because the clinical presentations can be similar. Red flags for PIRDs include multiple autoimmune diagnoses in the same patient, chronic lymphadenopathy, hepatomegaly, and/or splenomegaly, chronic colitis, hemophagocytic lymphohistiocytosis (HLH), Epstein Barr virus (EBV) susceptibility, recurrent or persistent fever, vasculitis, and sterile inflammation. For simplicity in this brief review, we limit our discussion of PIRDs to the following categories multiple autoimmune diseases, immune dysregulation with colitis, disorders with HLH and/or EBV susceptibility, autoinflammatory syndromes, type 1 interferonopathies, and disorders of sterile inflammation. Diagnosing a PIRD requires a broad immune evaluation for both immune system deficiencies and inflammation, along with genetic testing. Given the complex nature of these diseases, treatment often requires a team of subspecialists. Treatment, depending on the specific diagnosis, may be somewhat empiric with nonspecific immune modulators, symptom-directed therapies, and, in severe cases, hematopoietic stem cell transplantation; however, with the increasing number of biologics available, we are often able to use targeted immune therapy or even gene therapy.
{"title":"Immunodeficiency: Overview of primary immune regulatory disorders (PIRDs).","authors":"Cody S Nelson,Carolyn H Baloh","doi":"10.2500/aap.2024.45.240070","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240070","url":null,"abstract":"Primary immune regulatory disorders (PIRD) comprise a heterogeneous group of monogenic disorders that impact homeostatic control of inflammation and immune tolerance. Patients with a PIRD typically present to medical care with symptoms of autoimmunity or hyperinflammation as the dominant clinical feature, symptoms that include fever, rash, lymphadenopathy, organomegaly, arthritis, and colitis are commonplace. Notably, PIRDs are a distinct entity from primary immune deficiency disorders (PIDD), which are primarily defined by a qualitative or quantitative defect in immunity, which manifests as a susceptibility to recurrent infections. PIDDs and PIRDs can be challenging to differentiate because the clinical presentations can be similar. Red flags for PIRDs include multiple autoimmune diagnoses in the same patient, chronic lymphadenopathy, hepatomegaly, and/or splenomegaly, chronic colitis, hemophagocytic lymphohistiocytosis (HLH), Epstein Barr virus (EBV) susceptibility, recurrent or persistent fever, vasculitis, and sterile inflammation. For simplicity in this brief review, we limit our discussion of PIRDs to the following categories multiple autoimmune diseases, immune dysregulation with colitis, disorders with HLH and/or EBV susceptibility, autoinflammatory syndromes, type 1 interferonopathies, and disorders of sterile inflammation. Diagnosing a PIRD requires a broad immune evaluation for both immune system deficiencies and inflammation, along with genetic testing. Given the complex nature of these diseases, treatment often requires a team of subspecialists. Treatment, depending on the specific diagnosis, may be somewhat empiric with nonspecific immune modulators, symptom-directed therapies, and, in severe cases, hematopoietic stem cell transplantation; however, with the increasing number of biologics available, we are often able to use targeted immune therapy or even gene therapy.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269571","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240057
Vishaka R Hatcher,Veronica C Alix,Tasha S Hellu,Meredith M Schuldt
Specific antibody deficiency (SAD) is a common primary immunodeficiency disorder that should be considered in older children and adults with recurrent and/or severe sinopulmonary infections. The diagnosis is characterized by inadequate antibody response to polysaccharide vaccine, specifically, pneumococcal, with normal responses to protein antigens and normal levels of serum immunoglobulins as well as immunoglobulin G (IgG) subclasses. The underlying mechanism for SAD is not completely elucidated. It is understood that young children have limited polysaccharide responsiveness, which develops with increased age. Due to this phenomenon, the consensus is that there is adequate immune maturity after age 2 years, which is the earliest for the SAD diagnosis to be established. There remains a lack of consensus on thresholds for polysaccharide nonresponse, and there are several commercial laboratories that measure a range of serotypes, with the recommendation for patients to have their diagnostic evaluation with serotype testing both before vaccination and after vaccination to be conducted by the same laboratory. Once a diagnosis has been made, the management of SAD is based on the clinical severity. Clinicians may consider prophylactic antibiotics as well as immunoglobulin replacement. These patients should be closely followed up, with the possibility of discontinuation of IgG replacement after 12 to 24 months. Children are more likely to demonstrate resolution of SAD than are adolescents and adults. Patients with SAD may also progress to a more severe immunodeficiency; therefore, continued monitoring remains a crucial principle of practice in the care of patients with SAD.
特异性抗体缺乏症（SAD）是一种常见的原发性免疫缺陷疾病，对于反复发作和/或严重鼻窦肺部感染的年长儿童和成人，应考虑该病。其诊断特点是对多糖疫苗（尤其是肺炎球菌疫苗）的抗体反应不足，而对蛋白抗原的反应正常，血清免疫球蛋白和免疫球蛋白 G (IgG) 亚类的水平正常。SAD 的内在机制尚未完全阐明。据了解，幼儿对多糖的反应性有限，随着年龄的增长，这种反应性会逐渐增强。基于这一现象，目前的共识是，2 岁以后免疫系统就已充分成熟，这是确诊 SAD 的最早年龄。目前对多糖无应答的阈值仍未达成共识，有几家商业实验室可以检测一系列血清型，建议患者在接种疫苗前和接种疫苗后都由同一实验室进行血清型检测诊断评估。一旦确诊，将根据临床严重程度对 SAD 进行治疗。临床医生可考虑使用预防性抗生素和免疫球蛋白替代物。应对这些患者进行密切随访，可能在 12-24 个月后停止更换 IgG。与青少年和成人相比，儿童更有可能缓解 SAD。SAD 患者也可能发展为更严重的免疫缺陷；因此，持续监测仍是护理 SAD 患者的一项重要原则。
{"title":"Primary Immunodeficiency: Specific antibody deficiency with normal IgG.","authors":"Vishaka R Hatcher,Veronica C Alix,Tasha S Hellu,Meredith M Schuldt","doi":"10.2500/aap.2024.45.240057","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240057","url":null,"abstract":"Specific antibody deficiency (SAD) is a common primary immunodeficiency disorder that should be considered in older children and adults with recurrent and/or severe sinopulmonary infections. The diagnosis is characterized by inadequate antibody response to polysaccharide vaccine, specifically, pneumococcal, with normal responses to protein antigens and normal levels of serum immunoglobulins as well as immunoglobulin G (IgG) subclasses. The underlying mechanism for SAD is not completely elucidated. It is understood that young children have limited polysaccharide responsiveness, which develops with increased age. Due to this phenomenon, the consensus is that there is adequate immune maturity after age 2 years, which is the earliest for the SAD diagnosis to be established. There remains a lack of consensus on thresholds for polysaccharide nonresponse, and there are several commercial laboratories that measure a range of serotypes, with the recommendation for patients to have their diagnostic evaluation with serotype testing both before vaccination and after vaccination to be conducted by the same laboratory. Once a diagnosis has been made, the management of SAD is based on the clinical severity. Clinicians may consider prophylactic antibiotics as well as immunoglobulin replacement. These patients should be closely followed up, with the possibility of discontinuation of IgG replacement after 12 to 24 months. Children are more likely to demonstrate resolution of SAD than are adolescents and adults. Patients with SAD may also progress to a more severe immunodeficiency; therefore, continued monitoring remains a crucial principle of practice in the care of patients with SAD.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269579","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240028
Luigi D Notarangelo
Genetically determined defects of T-cell development comprise a heterogeneous group of conditions characterized by peripheral T-cell lymphopenia due to impaired intrathymic differentiation of T-cell progenitors. Collectively, these conditions are typically referred to as severe combined immune deficiency (SCID). In some cases (leaky SCID), residual function of the defective gene allows partial T-cell development. The vast majority of SCID disorders are due to genetic defects that affect the T-cell differentiation potential of hematopoietic stem cells, through a variety of mechanisms. However, some forms of SCID reflect impaired development or function of thymic stromal cells. A lack of peripheral T cells leads to increased susceptibility to severe infections since early in life. SCID is inevitably fatal unless immune reconstitution is achieved, most often through hematopoietic cell transplantation. Enzyme replacement therapy, gene therapy, and thymus implantation represent other forms of treatment in selected cases. The availability of newborn screening has greatly facilitated prompt recognition of SCID, which allows statistically significant improvement in survival after hematopoietic cell transplantation.
由基因决定的 T 细胞发育缺陷包括一组不同的病症，其特点是 T 细胞祖细胞胸膜内分化受损导致外周 T 细胞淋巴细胞减少。这些病症统称为严重合并免疫缺陷症（SCID）。在某些情况下（漏性 SCID），缺陷基因的残余功能允许部分 T 细胞发育。绝大多数 SCID 疾病是由于基因缺陷通过各种机制影响了造血干细胞的 T 细胞分化潜能。然而，某些形式的 SCID 反映了胸腺基质细胞的发育或功能受损。外周 T 细胞的缺乏会导致患者从生命早期开始就更容易受到严重感染。除非通过造血细胞移植实现免疫重建，否则 SCID 将不可避免地致命。酶替代疗法、基因疗法和胸腺植入术是针对特定病例的其他治疗方法。新生儿筛查的普及极大地促进了对 SCID 的及时识别，使造血细胞移植后的存活率在统计学上得到显著提高。
{"title":"Genetically-determined defects of T cell development.","authors":"Luigi D Notarangelo","doi":"10.2500/aap.2024.45.240028","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240028","url":null,"abstract":"Genetically determined defects of T-cell development comprise a heterogeneous group of conditions characterized by peripheral T-cell lymphopenia due to impaired intrathymic differentiation of T-cell progenitors. Collectively, these conditions are typically referred to as severe combined immune deficiency (SCID). In some cases (leaky SCID), residual function of the defective gene allows partial T-cell development. The vast majority of SCID disorders are due to genetic defects that affect the T-cell differentiation potential of hematopoietic stem cells, through a variety of mechanisms. However, some forms of SCID reflect impaired development or function of thymic stromal cells. A lack of peripheral T cells leads to increased susceptibility to severe infections since early in life. SCID is inevitably fatal unless immune reconstitution is achieved, most often through hematopoietic cell transplantation. Enzyme replacement therapy, gene therapy, and thymus implantation represent other forms of treatment in selected cases. The availability of newborn screening has greatly facilitated prompt recognition of SCID, which allows statistically significant improvement in survival after hematopoietic cell transplantation.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269575","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240049
David Mickey,Juanita Valdes Camacho,Adil Khan,David Kaufman
The immune system is divided into two major branches: innate and adaptive. The innate immune system is the body's first line of defense and rapidly responds in a nonspecific manner to various microorganisms, foreign materials, or injuries. Phagocytes, which include macrophages, monocytes, and neutrophils, are innate immune cells that can surround and kill microorganisms, ingest foreign material, and remove dead cells. They also indirectly boost both innate and adaptive immune responses through various activation signals. Phagocytic defects characteristically lead to fungal and bacterial infections of the respiratory tract, lymph nodes, skin, and other organ systems, and they are commonly associated with inflammatory bowel disease. This primer will review high-yield innate defects of phagocytic cells, including defects of respiratory (oxidative) burst, defects of neutrophil migration, cyclic and severe congenital neutropenias and associated disorders, and other phagocyte defect disorders.
{"title":"Immunodeficiency: Quantitative and qualitative phagocytic cell defects.","authors":"David Mickey,Juanita Valdes Camacho,Adil Khan,David Kaufman","doi":"10.2500/aap.2024.45.240049","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240049","url":null,"abstract":"The immune system is divided into two major branches: innate and adaptive. The innate immune system is the body's first line of defense and rapidly responds in a nonspecific manner to various microorganisms, foreign materials, or injuries. Phagocytes, which include macrophages, monocytes, and neutrophils, are innate immune cells that can surround and kill microorganisms, ingest foreign material, and remove dead cells. They also indirectly boost both innate and adaptive immune responses through various activation signals. Phagocytic defects characteristically lead to fungal and bacterial infections of the respiratory tract, lymph nodes, skin, and other organ systems, and they are commonly associated with inflammatory bowel disease. This primer will review high-yield innate defects of phagocytic cells, including defects of respiratory (oxidative) burst, defects of neutrophil migration, cyclic and severe congenital neutropenias and associated disorders, and other phagocyte defect disorders.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269576","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 : 2024-09-01DOI: 10.2500/aap.2024.45.240056
Mark Ballow
Quality of life (QOL) measures have become increasingly important in the management of patients with complex diseases. There are a number of instruments to measure QOL that include broad areas or domains of physical, psychological, social, spiritual, and environmental issues. The number of potential domains plus the large number of items within each domain have led to the development of a large variety of QOL instruments and of different approaches by using both health-related and non-health-related factors. Health-related QOL (HRQOL) measures have been incorporated into clinical trials to assess changes in the patient's perspective on his or her disease and the effects of treatment. An important aspect of these HR-QOL instruments is that these questionnaires are patient reported and usually self-administered. The life-long therapy of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) can be a challenge to the patient, his or her family and the physician. A number of patient-reported surveys have been published that examined treatment satisfaction and the comparison between IVIG and SCIG replacement therapy in patients with primary immunodeficiency. This review explores the use of HR-QOL surveys in patient preferences for mode and route of immunoglobulin therapy and site of care. Shared decision-making will be explored to emphasize the importance of this approach in optimizing patient care and compliance.
生活质量（QOL）测量在复杂疾病患者的管理中变得越来越重要。目前有许多测量 QOL 的工具，其中包括身体、心理、社会、精神和环境等广泛领域。潜在领域的数量加上每个领域内的大量项目，导致了大量 QOL 工具的开发，以及通过使用与健康相关和非健康相关因素的不同方法。与健康相关的 QOL（HRQOL）测量已被纳入临床试验，以评估病人对其疾病的看法和治疗效果的变化。这些健康相关 QOL 工具的一个重要方面是，这些问卷由患者报告，通常由患者自行填写。静脉注射免疫球蛋白（IVIG）或皮下注射免疫球蛋白（SCIG）的终身治疗对患者、患者家属和医生来说都是一项挑战。许多患者报告的调查报告都对原发性免疫缺陷患者的治疗满意度以及 IVIG 和 SCIG 替代治疗的比较进行了研究。本综述探讨了人力资源-QOL 调查在患者对免疫球蛋白治疗方式和途径以及治疗地点的偏好方面的应用。还将探讨共同决策，以强调这种方法在优化患者护理和依从性方面的重要性。
{"title":"Quality of life in primary immunodeficiency: Its contribution to shared decision-making and patient outcomes.","authors":"Mark Ballow","doi":"10.2500/aap.2024.45.240056","DOIUrl":"https://doi.org/10.2500/aap.2024.45.240056","url":null,"abstract":"Quality of life (QOL) measures have become increasingly important in the management of patients with complex diseases. There are a number of instruments to measure QOL that include broad areas or domains of physical, psychological, social, spiritual, and environmental issues. The number of potential domains plus the large number of items within each domain have led to the development of a large variety of QOL instruments and of different approaches by using both health-related and non-health-related factors. Health-related QOL (HRQOL) measures have been incorporated into clinical trials to assess changes in the patient's perspective on his or her disease and the effects of treatment. An important aspect of these HR-QOL instruments is that these questionnaires are patient reported and usually self-administered. The life-long therapy of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) can be a challenge to the patient, his or her family and the physician. A number of patient-reported surveys have been published that examined treatment satisfaction and the comparison between IVIG and SCIG replacement therapy in patients with primary immunodeficiency. This review explores the use of HR-QOL surveys in patient preferences for mode and route of immunoglobulin therapy and site of care. Shared decision-making will be explored to emphasize the importance of this approach in optimizing patient care and compliance.","PeriodicalId":520163,"journal":{"name":"Allergy & Asthma Proceedings","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269578","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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