ACAAI/AAAAI Inborn Errors of Immunity Guideline – Key Recommendations Guideline Bites

Guideline Resources

• Inborn Errors of Immunity
• American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology
• April 3, 2026
• Summary
• Full-text

Inborn Errors of Immunity Guideline (Clinical Approach to Diagnosis) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Clinical Approach to the Diagnosis of Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

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• The guideline recommends investigating for inborn errors of immunity diagnosis in patients with recurrent, severe, or rare infections, autoinflammation, autoimmunity, severe atopy, atypical malignancy, bone marrow failure, or combinations of these conditions. 
• The guideline recommends obtaining a detailed family history to support the IEI diagnosis and to identify undiagnosed affected relatives. 
• The guideline recommends an integrated approach for the diagnosis of a suspected IEI: clinical, immunologic, and genetic components. 
• The guideline recommends that the evaluation of immunodeficiency should include testing for secondary causes of immunodeficiency. 
• The guideline suggests consultation with a clinical immunology expert and multidisciplinary care for the evaluation and follow-up of suspected or diagnosed patients with IEI. 
• The guideline suggests the provision of supportive resources for patients and families diagnosed with IEI.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Newborn Screening for Severe Combined Immunodeficiency and Athymia—Diagnostic and Initial Approach. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Newborn Screening) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Newborn Screening for Severe Combined Immunodeficiency and Athymia—Diagnostic and Initial Approach from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

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• The guideline recommends T-cell receptor excision circle, or TREC, quantitation for newborn population-based screening for the early identification of newborns with severe combined immunodeficiency, or SCID, and complete athymia. 
• The guideline recommends the urgent confirmation of an abnormal newborn screening or NBS for SCID with complete blood counts with differential and flow cytometric measurement of peripheral blood lymphocyte subset populations, including assessment of numbers of T, B, and NK subsets and naive T cells. 
• The guideline recommends that diagnostic evaluation for SCID and athymia includes genetic testing, ascertainment of maternal T-cell engraftment, IgE levels, eosinophilia, T-cell oligoclonality, Tcell proliferation, and adenosine deaminase enzyme activity.
• The guideline recommends urgent referral to centers with expertise in the care of severe immunodeficiency after SCID or athymia diagnosis is confirmed. 
• The guideline recommends referral to clinicians with expertise in inborn errors of immunity, or IEI for assessment and diagnosis of patients with non-SCID T-cell lymphopenia detected by NBS.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Genetic Evaluation of Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Genetic Evaluation) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Genetic Evaluation of Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends single-gene sequencing to test patients with suspected IEI who have a similarly affected family member with a known genetic defect or who present with a condition with a defect in a gene that might not be reliably analyzed using high-throughput massively parallel sequencing. 
• The guideline recommends targeted gene panel sequencing including genes associated with IEI or exome sequencing as an initial step for genetic diagnosis, when a familial gene defect does not explain the patient’s condition. 
• The guideline suggests whole genome sequencing of individuals with suspected IEI and non-immunologic traits or with high suspicion for a noncoding genetic defect. 
• The guideline recommends DNA copy number variant testing in patients with IEI with a suspected gene(s) deletion or duplication. 
• The guideline recommends the American College of Medical Genetics and Genomics guidelines for evaluating gene variant pathogenicity. 
• The guideline recommends familial genetic testing to aid in gene variant pathogenicity resolution. 
• The guideline suggests familial genetic testing to ascertain risk of disease in currently unaffected relatives. 
• The guideline recommends investigating multiple genetic diagnoses when a monogenic diagnosis does not explain the patient’s clinical characteristics. 
• The guideline recommends that genetic testing for patients with IEI can be ordered by clinicians with expertise in IEI.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Immunologic Diagnosis of Predominantly Antibody Deficiencies. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Antibody Deficiencies) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Immunologic Diagnosis of Predominantly Antibody Deficiencies from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends that patients with suspected antibody deficiencies be evaluated with immunoglobulin measurement, antigen-specific antibody responses, and lymphocyte phenotyping and exclusion of secondary causes. 
• The guideline recommends the diagnosis of agammaglobulinemia for patients with low or undetectable serum immunoglobulin concentrations and low or undetectable circulating B lymphocytes and normal total CD3+ T cell numbers. 
• The guideline recommends the diagnosis of common variable immune deficiency for patients with low serum IgG and low serum IgA and/or low IgM levels and demonstrated impaired antibody response to infection or immunization and other causes of hypogammaglobulinemia have been excluded.
• The guideline recommends the diagnosis of selective IgA deficiency for patients older than 4 years of age with serum IgA level below the limit of detection and normal serum IgG and IgM levels. 
• The guideline suggests the diagnosis of IgG subclass deficiency for patients with recurrent infections and low levels of 1 or more serum IgG subclass levels and normal serum total IgG levels. 
• The guideline suggests the diagnosis of specific antibody deficiency to polysaccharides for patients with recurrent respiratory infections and impaired antibody responses to polysaccharides and normal serum total IgG levels. 
• The guideline suggests the diagnosis of SAD to protein antigen for patients with recurrent infections and impaired antibody responses to protein antigen immunizations and normal serum total IgG levels. 
• The guideline recommends that patients with low serum IgG and IgA levels and normal or elevated serum IgM level be given the diagnosis of immunoglobulin classswitch defects after ruling out combined immunodeficiencies that present with similar laboratory findings. 
• The guideline recommends the diagnosis of transient hypogammaglobulinemia of infancy for infants and children with low serum IgG level and normal antibody response to immunizations and absent evidence of secondary causes. 
• The guideline suggests the diagnosis of unspecified primary hypogammaglobulinemia for patients with recurrent infections and low serum IgG level and normal cellular immunity and absent evidence of secondary causes of low IgG levels and not fulfilling diagnostic criteria for the above-mentioned antibody deficiency disorders. 

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Diagnosis of Combined Immunodeficiencies, Phagocyte Defects, InnateImmune Defects, and Complement Deficiencies. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Immunodeficiencies & more) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Diagnosis of Combined Immunodeficiencies, Phagocyte Defects, Innate Immune Defects, and Complement Deficiencies from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends immunologic investigations in patients with infectious manifestations, autoimmunity, malignancy, or organ-specific pathologies, suggesting cellular and humoral immunodeficiency. 
• The guideline recommends the diagnosis of combined immunodeficiency, or CID for patients with impairment of both cellular and antibody immune functions. 
• The guideline recommends immunologic investigations and testing of diagnostic biological markers in patients with suspicion of CID and certain specific clinical findings in non-immunologic organs and systems. 
• The guideline suggests periodic assessments of immunologic function in patients with CID and syndromic features. 
• The guideline recommends that patients with suspected quantitative neutrophil defects be screened with serial CBCs with differential. 
• The guideline recommends that patients with suspected Leukocyte Adhesion Deficiency (LAD) be tested with flow cytometry analysis of relevant phagocyte surface molecules for LAD I and II, and targeted genetic testing for LAD I, II, III and IV.
• The guideline recommends that patients with suspected chronic granulomatous disease (CGD) have measurement of phagocyte oxidase activity and genetic testing for CGD associated gene defects. 
• The guideline recommends that patients with pulmonary alveolar proteinosis be tested for pathogenic variants in the genes encoding the GM-CSF receptor and for autoantibodies to GM-CSF.
• The guideline recommends that patients with suspected inherited susceptibility to a specific pathogen(s) be investigated for associated gene defects of innate immunity in addition to exclusion of adaptive immune defects and secondary causes of immune defects. 
• The guideline recommends that patients with recurrent or severe infections by encapsulated bacteria and with normal antibody responses be evaluated for complement deficiency. 
• The guideline recommends that patients presenting with thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure be screened for abnormalities of complement regulatory proteins and/or autoantibodies against complement Factor H . 
• The guideline recommends genetic testing when complement function screening is abnormal.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Immunologic Diagnosis of Primary Immune Dysregulation Disorders and Autoinflammatory Disorders. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Immunologic Diagnosis of Disorders) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Immunologic Diagnosis of Primary Immune Dysregulation Disorders and Autoinflammatory Disorders from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends evaluation for IEI in patients with clinical manifestations of immune dysregulation, such as immunodeficiency, autoimmunity, lymphoproliferation, and autoinflammation. 
• The guideline recommends the assessment of cellular and humoral immunologic functions in patients with suspected primary immune dysregulation disorders. 
• The guideline recommends that patients with periodic fevers and chronic systemic inflammation should be evaluated for IEI and secondary causes such as infection, autoimmune disease, or malignancy. 
• The guideline recommends that patients who exhibit lymphoproliferation and autoimmunity be evaluated for primary and secondary immune dysregulation syndromes.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Surveillance of Potential Clinical Manifestations in Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Surveillance in IEI) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Surveillance of Potential Clinical Manifestations in Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline suggests the evaluation of growth and nutritional status in patients with IEI. 
• The guideline suggests testing for specific infectious pathogens in patients with IEI known to be associated with high morbidity and mortality to these infections.
• The guideline recommends the assessment of complete blood cell counts with differential in patients with IEI. 
• The guideline recommends against routine screening for autoantibodies, given the high proportion of asymptomatic patients with autoantibodies in circulation. 
• The guideline recommends the evaluation for major organ system functions and screening for cancer and mental health disorders in patients with IEI.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Genetic Evaluation of Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Immunoglobulin Replacement) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Immunoglobulin Replacement from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends immunoglobulin replacement therapy for patients with IEI with IgG antibody deficiency. 
• The guideline recommends that initial dosing of immunoglobulin for replacement therapy be at 400 mg/kg to 600 mg/kg per month, followed by dose adjustment, if necessary. 
• The guideline recommends the monitoring of serum IgG levels, complete blood cell counts with differential, and serum chemistry panel for patients on immunoglobulin replacement therapy. 
• The guideline recommends maintaining serum IgG levels at more than 800 mg/dL to improve outcomes. 
• The guideline recommends that immunoglobulin replacement therapy is indicated as a continuous therapy for IEI. 
• The guideline recommends that a low or absent IgA level, in the setting of low IgG levels, is not a contraindication for immunoglobulin replacement therapy. 
• The guideline suggests that the route of immunoglobulin replacement therapy be determined based on patient tolerance or preference.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Infection Prevention in Inborn Errors of Immunity, Management of Co-Morbidities in Inborn Errors of Immunity, and Immunizations in the Management of Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com. 

Inborn Errors of Immunity Guideline (Infection Prevention & Management) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the sections on Infection Prevention in Inborn Errors of Immunity, Management of Co-Morbidities in Inborn Errors of Immunity, and Immunizations in the Management of Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends targeted antimicrobial prophylaxis for patients with IEI and increased susceptibility to infections. 
• The guideline recommends using only irradiated, CMV-negative, lymphocyte-depleted blood products for administration to patients with combined immunodeficiencies or athymia. 
• The guideline recommends educating patients regarding environmental exposures that may increase the risk of infections for patients with IEI. 
• The guideline suggests prompt diagnostic testing in patients with IEI with acute infection symptoms and the use of antimicrobial regimens with duration longer than recommended for immunocompetent patients. 
• The guideline suggests that systemic comorbidities in patients with IEI should be evaluated and managed with a multidisciplinary team with expertise in IEIrelated comorbidities.
• The guideline recommends prompt management of cytopenia(s) or malignancies in patients with IEI. 
• The guideline recommends the use of vaccine recommendations from public agencies and professional medical organizations for patients with IEI. 

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Immune Reconstitution Therapy for Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Immune Reconstitution Therapy) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Immune Reconstitution Therapy for Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline suggests that allogeneic hematopoietic stem cell transplantation, or HSCT for patients with IEI be performed at a center with experience in HSCT for IEI. 
• The guideline recommends that patients with typical SCID or leaky/atypical SCID receive definitive therapy with allogeneic HSCT or gene therapy.
• The guideline recommends that patients with congenital athymia disorders be treated with cultured thymus tissue implantation (CTTI). 
• The guideline recommends that patients with CID disorders who have severe cellular immune defects or who manifest severe or refractory disease complications be considered for allogeneic HSCT. 
• The guideline recommends that patients with primary hemophagocytic lymphohystiocytosis, or HLH disorders and patients with X-linked lymphoproliferative disease type 1 be evaluated for allogeneic HSCT. 
• The guideline suggests that patients with immune dysregulation who manifest severe or refractory disease complications be evaluated for allogeneic HSCT. 
• The guideline recommends HSCT for patients with defects in neutrophil number or function associated with severe clinical phenotypes. 
• The guideline suggests HSCT in patients with innate immune defects affecting hematopoietic cell lineages and who manifest with recurrent, persistent severe infections. 
• The guideline recommends that any patient with IEI who receives definitive treatment with HSCT, CTTI, or gene therapy receive life-long follow-up by clinicians experienced in evaluating immune reconstitution and monitoring for long-term complications of these procedures.

And there you have it. Stay tuned for our next Guideline Bite, where we’ll go over recommendations on Precision Medicine in Inborn Errors of Immunity and Quality of Life in Inborn Errors of Immunity. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

Inborn Errors of Immunity Guideline (Precision Medicine and QoL) Guideline Video

Video Transcription

In today’s Guideline Bite we'll be going over the section on Precision Medicine in Inborn Errors of Immunity and Quality of Life in Inborn Errors of Immunity from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology’s guideline on Inborn Errors of Immunity (IEI).

Let’s get started.

• The guideline recommends performing quality-of life (QoL) measurements in patients with IEI, inclusive of patient-reported outcome (PRO) measurements conducted with a validated tool. 
• The guideline suggests that PROs should be measured using a disease-specific QoL instrument and at important management changes in the patient’s clinical journey. 
• The guideline suggests that patients with IEI have perceived health assessed at each clinical encounter. 
• The guideline suggests that patients with IEI be assessed for fatigue at each clinical encounter. 
• The guideline suggests implementing shared decision making between the provider and the patient as part of clinical care to improve QoL and patient satisfaction.

And there you have it. Make sure to check out the full guideline from the American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma and Immunology on guidelinecentral.com.

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