Allergy And Asthma Proceedings[JOURNAL]
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200 papers
Integrating innovation and shared decision-making in allergy and immunology practice.
Bellanti JA, Settipane RA
Allergy Asthma Proc · 2024 Nov · PMID 39517073 · Full text
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A systematic review and meta-analysis exploring the bidirectional association between asthma and gastroesophageal reflux disease in children.
Zheng K, Wang X, Tang L … +3 more , Chen L, Zhao Y, Chen X
Allergy Asthma Proc · 2024 Nov · PMID 39517072 · Publisher ↗
Asthma is the most prevalent chronic respiratory disease in children, and gastroesophageal reflux disease (GERD) is one of its extraesophageal complications of asthma. Both conditions are commonly observed in pediatric o...
Asthma is the most prevalent chronic respiratory disease in children, and gastroesophageal reflux disease (GERD) is one of its extraesophageal complications of asthma. Both conditions are commonly observed in pediatric outpatient clinics, but the causality between them in children is still debated. Therefore, we conducted a systematic review and meta-analysis to evaluate the bidirectional association between asthma and GERD in children. We systematically reviewed original studies published from January 2000 to February 2024 by searching the data bases. We also performed manual retrieval and screening to identify studies that met the inclusion criteria. The quality of the final included studies was evaluated by using the Newcastle-Ottawa Scale, and outcome measures were extracted. We identified nine eligible studies, which included 304,399 children of different ages from seven countries. Overall, the risk of developing GERD in children with asthma (odds ratio [OR] 2.16 [95% confidence interval [CI], 1.6-2.91) was higher than the risk of developing asthma in children with GERD (OR 1.55 [95% CI, 1.32-1.82]). Based on the available studies, it can be concluded that asthma and GERD are mutually aggravating factors in children, presenting a bidirectional association. However, the risk of developing GERD in children with asthma is higher to some extent. More large-scale and high-quality prospective cohort studies are needed in the future to provide richer evidence and more research opportunities.
Dupilumab rapidly improves eustachian tube dysfunction and otologic symptoms in aspirin-exacerbated respiratory disease.
Mullur J, Lundberg M, Maurer R … +2 more , Laidlaw TM, Buchheit KM
Allergy Asthma Proc · 2024 Nov · PMID 39517071 · Full text
Patients with aspirin-exacerbated respiratory disease (AERD) frequently experience symptoms consistent with eustachian tube dysfunction (ETD), which can substantially impair patient quality of life. We analyzed a cohort...
Patients with aspirin-exacerbated respiratory disease (AERD) frequently experience symptoms consistent with eustachian tube dysfunction (ETD), which can substantially impair patient quality of life. We analyzed a cohort of 98 adult patients with AERD who participated in a longitudinal, survey-based study. By assessing data over 1 year, we established that, in patients with AERD, the ear/facial subdomain of the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire could predict performance on the 7-item Eustachian Tube Dysfunction Questionnaire, a validated instrument for the diagnosis of ETD. We then performed a re-analysis of data from a prospective, open-label study of 22 adult patients with AERD treated with dupilumab for 3 months. We found that treatment with dupilumab was associated with a significant decrease in the SNOT-22 ear/facial subdomain score, which reflects a substantial reduction in otologic symptoms and ETD within 1 month of initiating dupilumab and was sustained for 3 months afterward. Our findings provide evidence that dupilumab significantly improved ETD and otologic symptoms in AERD, evidenced by changes in the SNOT-22 ear/facial subdomain score. The presence of ETD and otologic symptoms should be considered when determining the optimal therapeutic course for patients with AERD.
The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis.
Huang YC, Caldarone L, Sherman C … +3 more , Deutsch R, Ahn J, Bellanti JA
Allergy Asthma Proc · 2024 Nov · PMID 39517070 · Full text
Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 20...
Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 2020. Current analyses provided by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of messenger RNA (mRNA) 1273 and BNT162b2 vaccines administered, respectively. The mechanisms by which these mRNA vaccines induce adverse vaccine reactions have been the subject of conflicting reports. Although skin testing with excipient components found in mRNA-1273 and BNT162b2 vaccines, such as polyethylene glycol (PEG) and related vaccine lipid products, were originally recommended to identify potential predictive biomarkers of adverse allergic reactions, more recent evidence has suggested that routine skin testing with these vaccine excipients have poor predictability and do not correlate with susceptibility to vaccine injury. The goal of this proof-of-concept (POC) exploratory study was to investigate the role of leukocyte activation (LA) induced by lipid excipients found in mRNA COVID-19 vaccines in the pathogenesis of COVID-19 mRNA vaccine-associated adverse reactions by using an LA assay developed in our laboratory. An LA assay was performed on blood samples obtained from 30 study subjects who were assigned to three study groups: group 1 consisted of 10 subjects who had received an mRNA COVID-19 vaccine and developed a serious vaccine adverse reaction; group 2 consisted of 10 subjects who had received a COVID-19 vaccine and developed a mild adverse reaction; and group 3 consisted of 10 subjects who had not received a COVID-19 vaccine and were asymptomatic. Five excipients were tested in each of the 10 subjects; hence, a potential of 50 reactions could be expressed in each of the three groups. In the subjects in group 1 who had shown clinically severe vaccine effects, 8 of 50 (16%) had severe LA index (LAI) responses (>144.83), 12 of 50 (24%) had moderate LAI responses (87.62 -144.82), and 30 of 50 (60%) had no reaction (0 - 87.61). In the subjects in group 2 who had shown clinically mild vaccine effects, 4 of 50 (8%) had severe LAI responses (>144.83), 9 of 50 (18%) had moderate LAI responses (87.62 -144.82), and 37 of 50 (74%) had no reaction. In the subjects in group 3 who had not received the vaccine and, therefore, had no clinical vaccine effects, 2 of 50 (4%) had severe LAI responses (>144.83), 10 of 50 (20%) had moderate LAI responses (87.62 -144.82), and 38 of 50 (76%) had no reaction LA index (LAI) responses. The results of this exploratory POC study suggest that the measurement of LA induced by PEG and other vaccine-related lipid excipients found in mRNA COVID-19 vaccines may provide a novel and useful predictive biomarker associated with adverse non-immunoglobulin E (IgE) related allergic reactions to these vaccines. The study results also underscore growing concerns related to these non-IgE hypersensitivity reactions and their potential for pathogenesis of adverse vaccine reactions. This is particularly noteworthy because, with the continuing emergence of novel and evolving variants of severe acute respiratory syndrome corona-virus 2 mutants, yearly immunization with mRNA vaccines will most likely be recommended. Although the study was not sufficiently powered to draw definitive conclusions with regard to associations between vaccine-associated COVID-19 reactions and LA, the trends of a more severe set of clinical reactions seen associated with LAI reactivity scores, particularly with ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), suggest a potential benefit worthy of exploration in future randomized controlled trials.
For the patient.
Allergy Asthma Proc · 2024 Nov · PMID 39517069 · Publisher ↗
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Immunodeficiency: Overview of primary immune regulatory disorders (PIRDs).
Nelson CS, Baloh CH
Allergy Asthma Proc · 2024 Sep · PMID 39294916 · Full text
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 car...
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.
Essentials of an immunodeficiency primer: A practical reference for the allergist/immunologist and the allergy-immunology fellow-in-training (FIT).
Bellanti JA, Settipane RA
Allergy Asthma Proc · 2024 Sep · PMID 39294915 · Full text
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Immunodysregulation in immunodeficiency.
Chang C
Allergy Asthma Proc · 2024 Sep · PMID 39294914 · Publisher ↗
The primary immunodeficiency diseases are often accompanied by autoimmunity, autoinflammatory, or aberrant lymphoproliferation. The paradoxical nature of this association can be explained by the multiple cells and molecu...
The primary immunodeficiency diseases are often accompanied by autoimmunity, autoinflammatory, or aberrant lymphoproliferation. The paradoxical nature of this association can be explained by the multiple cells and molecules involved in immune networks that interact with each other in synergistic, redundant, antagonistic, and parallel arrangements. Because progressively more immunodeficiencies are found to have a genetic etiology, in many cases, a monogenic pathology, an understanding of why immunodeficiency is really an immune dysfunction becomes evident. Understanding the role of specific genes allows us to better understand the complete nature of the inborn error of immunity (IEI); the latter is a term generally used when a clear genetic etiology can be discerned. Autoimmune cytopenias, inflammatory bowel disease, autoimmune thyroiditis, and autoimmune liver diseases as well as lymphomas and cancers frequently accompany primary immunodeficiencies, and it is important that the practitioner be aware of this association and to expect that this is more common than not. The treatment of autoimmune or immunodysregulation in primary immunodeficiencies often involves further immunosuppression, which places the patient at even greater risk of infection. Mitigating measures to prevent such an infection should be considered as part of the treatment regimen. Treatment of immunodysregulation should be mechanism based, as much as we understand the pathways that lead to the dysfunction. Focusing on abnormalities in specific cells or molecules, cytokines, will become increasingly used to provide a targeted approach to therapy, a prelude to the success of personalized medicine in the treatment of IEIs.
Immunoglobulin therapy for immunodeficiency.
Wilson BE, Freeman CM
Allergy Asthma Proc · 2024 Sep · PMID 39294913 · Publisher ↗
Immunoglobulin replacement is donor-derived pooled immunoglobulin G, which provides passive immunity to patients with antibody deficiency or dysfunction. It may be administered either intravenous or subcutaneous routes....
Immunoglobulin replacement is donor-derived pooled immunoglobulin G, which provides passive immunity to patients with antibody deficiency or dysfunction. It may be administered either intravenous or subcutaneous routes. Intravenous immunoglobulin is administered at higher doses every 3-4 weeks, whereas most forms of subcutaneous immunoglobulin are administered at lower doses, usually every 1-2 weeks. Benefits and risks, including adverse effects, convenience, and cost vary according to route of administration. Immunoglobulin products also differ in their composition, so patient-specific comorbidities are important to consider when selecting an immunoglobulin product. We discuss adverse effects associated with immunoglobulin therapy, their associated risk factors, treatment, and ways to mitigate these risks. Finally, the laboratory monitoring and vaccination recommendations for patients on immunoglobulin replacement therapy are reviewed.
Immunodeficiency: Quantitative and qualitative phagocytic cell defects.
Mickey D, Camacho JV, Khan A … +1 more , Kaufman D
Allergy Asthma Proc · 2024 Sep · PMID 39294912 · Publisher ↗
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 mate...
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.
Primary antibody deficiencies.
Nguyen AT, Aquino MR
Allergy Asthma Proc · 2024 Sep · PMID 39294911 · Publisher ↗
Primary antibody deficiencies are characterized by the inability to effectively produce antibodies and may involve defects in B-cell development or maturation. Primary antibody deficiencies can occur at any age, dependin...
Primary antibody deficiencies are characterized by the inability to effectively produce antibodies and may involve defects in B-cell development or maturation. Primary antibody deficiencies can occur at any age, depending on the disease pathology. Certain primary antibody deficiencies affect males and females equally, whereas others affect males more often. Patients typically present with recurrent sinopulmonary and gastrointestinal infections, and some patients can experience an increased risk of opportunistic infections. Multidisciplinary collaboration is important in the management of patients with primary antibody deficiencies because these patients require heightened monitoring for atopic, autoimmune, and malignant comorbidities and complications. The underlying genetic defects associated with many primary antibody deficiencies have been discovered, but, in some diseases, the underlying genetic defect and inheritance are still unknown. The diagnosis of primary antibody deficiencies is often made through the evaluation of immunoglobulin levels, lymphocyte levels, and antibody responses. A definitive diagnosis is obtained through genetic testing, which offers specific management options and may inform future family planning. Treatment varies but generally includes antibiotic prophylaxis, vaccination, and immunoglobulin replacement. Hematopoietic stem cell transplantation is also an option for certain primary antibody deficiencies.
Immunodeficiency: Burden of Illness.
Hsueh JC, Van Hersh AT, Zhao W
Allergy Asthma Proc · 2024 Sep · PMID 39294910 · Publisher ↗
Immunodeficiency disorders pose substantial burdens on the health-care system and the patients affected. Broadly, immunodeficiencies can be divided into primary immunodeficiency disorders (PIDDs) and secondary immunodefi...
Immunodeficiency disorders pose substantial burdens on the health-care system and the patients affected. Broadly, immunodeficiencies can be divided into primary immunodeficiency disorders (PIDDs) and secondary immunodeficiency disorders. This review will focus on PIDDs. The overall prevalence for PIDDs is estimated to be ∼1-2% of the population but may be underestimated due to underdiagnosis of these conditions. PIDDs affect males slightly more often than females. The mortality rates differ based on the specific condition but can be extremely high if the condition is left undiagnosed or untreated. The most common causes of death are infections, respiratory complications, and cancers (e.g., lymphoma). Comorbidities and complications include infection, chronic lung disease, granulomatous lymphocytic interstitial lung disease, and autoimmune disorders. The disease burden of patients with common variable immunodeficiency (CVID) is estimated to be greater than patients with diabetes mellitus and chronic obstructive pulmonary disease. PIDDs have a serious impact on the quality of life of the patients, including sleep disturbance, anxiety, and social participation as well as other psychosocial burdens associated with these disorders. The financial cost of PIDDs can be substantial, with the cost of untreated CVID estimated to be $111,053 per patient per year. Indirect costs include productivity loss and time lost due to infusion and hospital visits. Secondary immunodeficiency is not fully discussed in this review but likely contributes equally to the burden of overall immunodeficiency disorders. Management of patients with PIDDs should use a comprehensive approach, including medical, nursing, psychiatric, and quality of life, to improve the outcome.
Hematopoietic stem cell transplantation for primary immunodeficiency.
Alsaati N, Grier A, Ochfeld E … +2 more , McClory S, Heimall J
Allergy Asthma Proc · 2024 Sep · PMID 39294909 · Publisher ↗
Primary immunodeficiencies, also commonly called inborn errors of immunity (IEI), are commonly due to developmental or functional defects in peripheral blood cells derived from hematopoietic stem cells. In light of this,...
Primary immunodeficiencies, also commonly called inborn errors of immunity (IEI), are commonly due to developmental or functional defects in peripheral blood cells derived from hematopoietic stem cells. In light of this, for the past 50 years, hematopoietic stem cell transplantation (HSCT) has been used as a definitive therapy for IEI. The fields of both clinical immunology and transplantation medicine have had significant advances. This, in turn, has allowed for both an increasing ability to determine a monogenic etiology for many IEIs and an increasing ability to successfully treat these patients with HSCT. Therefore, it has become more common for the practicing allergist/immunologist to diagnose and manage a broad range of patients with IEI before and after HSCT. This review aims to provide practical guidance for the clinical allergist/immunologist on the basics of HSCT and known outcomes in selected forms of IEI, the importance of pre-HSCT supportive care, and the critical importance of and guidance for life-long immunologic and medical monitoring of these patients.
Overview of secondary immunodeficiency.
Herman KE, Tuttle KL
Allergy Asthma Proc · 2024 Sep · PMID 39294908 · Publisher ↗
In contrast to inborn errors of immunity (IEI), which are inherited disorders of the immune system that predispose to infections, malignancy, atopy, and immune dysregulation, secondary immunodeficiencies and immune dysre...
In contrast to inborn errors of immunity (IEI), which are inherited disorders of the immune system that predispose to infections, malignancy, atopy, and immune dysregulation, secondary immunodeficiencies and immune dysregulation states (SID) are acquired impairments in immune cell function and/or regulation, and may be transient, reversible, or permanent. SIDs can derive from a variety of medical comorbidities, including protein-losing conditions, malnutrition, malignancy, certain genetic syndromes, prematurity, and chronic infections. Medications, including immunosuppressive and chemotherapeutic drugs, can have profound effects on immunity and biologic agents used in rheumatology, neurology, and hematology/oncology practice are increasingly common causes of SID. Iatrogenic factors, including surgical procedures (thymectomy, splenectomy) can also contribute to SID. A thorough case history, medication review, and laboratory evaluation are necessary to identify the primary driver and determine proper management of SID. Careful consideration should be given to whether a primary IEI could be contributing to autoimmunity, malignancy, and posttreatment complications (e.g., antibody deficiency). SID management consists of addressing the driving condition and/or removing the offending agent if feasible. If SID is suspected to be permanent, then antibiotic prophylaxis, additional immunization, and immunoglobulin replacement should be considered.
Genetically-determined defects of T cell development.
Notarangelo LD
Allergy Asthma Proc · 2024 Sep · PMID 39294907 · Full text
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. Collecti...
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.
Immunodeficiency: Complement disorders.
McMurray JC, Schornack BJ, Weskamp AL … +8 more , Park KJ, Pollock JD, Day WG, Brockshus AT, Beakes DE, Schwartz DJ, Mikita CP, Pittman LM
Allergy Asthma Proc · 2024 Sep · PMID 39294906 · Full text
The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lec...
The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lectin pathways augment the innate response. Impairment, deficiency, or overactivation of any of the known 50 complement proteins may lead to increased susceptibility to infection with encapsulated organisms, autoimmunity, hereditary angioedema, or thrombosis, depending on the affected protein. Classic pathway defects result from deficiencies of complement proteins C1q, C1r, C1s, C2, and C4, and typically manifest with features of systemic lupus erythematosus and infections with encapsulated organisms. Alternative pathway defects due to deficiencies of factor B, factor D, and properdin may present with increased susceptibility to Neisseria infections. Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) and ficolin 3, may be asymptomatic or lead to pyogenic infections and autoimmunity. Complement protein C3 is common to all pathways, deficiency of which predisposes patients to severe frequent infections and glomerulonephritis. Deficiencies in factor H and factor I, which regulate the alternative pathway, may lead to hemolytic uremic syndrome. Disseminated Neisseria infections result from terminal pathway defects (i.e., C5, C6, C7, C8, and C9). Diagnosis of complement deficiencies involves screening with functional assays (i.e., total complement activity [CH50], alternative complement pathway activity [AH50], enzyme-linked immunosorbent assay [ELISA]) followed by measurement of individual complement factors by immunoassay. Management of complement deficiencies requires a comprehensive and individualized approach with special attention to vaccination against encapsulated bacteria, consideration of prophylactic antibiotics, treatment of comorbid autoimmunity, and close surveillance.
Quality of life in primary immunodeficiency: Its contribution to shared decision-making and patient outcomes.
Ballow M
Allergy Asthma Proc · 2024 Sep · PMID 39294905 · Publisher ↗
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, psy...
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.
Primary Immunodeficiency: Specific antibody deficiency with normal IgG.
Hatcher VR, Alix VC, Hellu TS … +1 more , Schuldt MM
Allergy Asthma Proc · 2024 Sep · PMID 39294904 · Full text
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 characterize...
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.
Isotype deficiencies (IgG subclass and selective IgA, IgM, IgE deficiencies).
Imam K, Huang J, White AA
Allergy Asthma Proc · 2024 Sep · PMID 39294903 · Publisher ↗
Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. These isotype deficiencies have a variable presentation from asymp...
Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. These isotype deficiencies have a variable presentation from asymptomatic to recurrent infections resistant to prophylactic antibiotics. 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. 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.
Diagnostic tests for primary immunodeficiency disorders: Classic and genetic testing.
Klangkalya N, Fleisher TA, Rosenzweig SD
Allergy Asthma Proc · 2024 Sep · PMID 39294902 · Full text
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 auto...
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.
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