Today, we are outlining key recommendations from the American College of Allergy, Asthma, and Immunology (ACAAI) and American Academy of Allergy, Asthma & Immunology (AAAAI) guideline, Inborn Errors of Immunity. 

The 2026 ACAAI/AAAAI guideline update builds on the 2015 guideline, outlining the many advances in the care and diagnosis of patients with primary immune deficiency disorders (now also known as IEI). Although the guideline includes more than 70 recommendations, we curated a selection of key recommendations below. The following recommendations discuss clinical approaches to diagnosing IEI, genetic evaluation of IEI, surveillance of potential clinical manifestations in IEI, and more.

For a complete look at all the recommendations included in the 2026 update, view the full-text version. 

Key Elements of the 2026 Update

Clinical Approach to the Diagnosis of Inborn Errors of Immunity 

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

Genetic Evaluation of Inborn Errors of Immunity

  • We recommend 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.
  • We recommend 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.
  • We suggest whole genome sequencing of individuals with suspected IEI and non-immunologic traits or with high suspicion for a noncoding genetic defect.
  • We recommend DNA copy number variant testing in patients with IEI with a suspected gene(s) deletion or duplication.
  • We recommend the American College of Medical Genetics and Genomics (ACMG) guidelines for evaluating gene variant pathogenicity.
  • We recommend familial genetic testing to aid in gene variant pathogenicity resolution.
  • We suggest familial genetic testing to ascertain risk of disease in currently unaffected relatives.
  • We recommend investigating multiple genetic diagnoses when a monogenic diagnosis does not explain the patient's clinical characteristics.
  • We recommend that genetic testing for patients with IEI can be ordered by clinicians with expertise in IEI.

Surveillance of Potential Clinical Manifestations in Inborn Errors of Immunity

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

Infection Prevention in Inborn Errors of Immunity

  • We recommend targeted antimicrobial prophylaxis for patients with IEI and increased susceptibility to infections.
  • We recommend using only irradiated, cytomegalovirus (CMV)-negative, lymphocyte-depleted blood products for administration to patients with combined immunodeficiencies or athymia.
  • We recommend educating patients regarding environmental exposures that may increase the risk of infections for patients with IEI.
  • We suggest 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.

Immunizations in the Management of Inborn Errors of Immunity

  • We recommend the use of vaccine recommendations from public agencies (eg, WHO and CDC) and professional medical organizations (eg, AAAAI, ACAAI, and CIS) for patients with IEI.

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