Inborn Errors of Immunity in Iran: Epidemiology, Diagnostic Framework, and Future Directions
Epidemiology and Genetic Landscape
Inborn errors of immunity (IEI) are expected to be more prevalent in Iran than in many other regions, largely due to the high rate of consanguinity. This unique genetic background has enabled the discovery of numerous novels and complex IEI-associated genes, contributing to the global understanding of immune function. Despite these advances, many affected individuals remain undiagnosed, underscoring the gap between genetic potential and clinical recognition.
Diagnostic Pathways and Infrastructure
Diagnosis of IEI in Iran follows a structured, multidisciplinary pathway. Patients with suspected disease are first assessed by clinical immunologists, who collect detailed clinical and immunological data and initiate targeted laboratory investigations. When genetic etiology is suspected, patients are referred to clinical geneticists for advanced testing and variant interpretation. Specialized immunology and genetics departments exist in most provincial capitals, while inter-institutional collaborations help ensure that patients from underserved regions can also access comprehensive diagnostic services.
Genetic testing is primarily conducted in academic medical centers, national research institutes, and select private laboratories. Methods employed include:
- Sanger sequencing for known familial mutations or hotspot variants (turnaround: 2–4 weeks).
- NGS-based gene panels.
- Whole-exome and whole-genome sequencing (WES/WGS), increasingly available through international collaborations (turnaround: 2–6 months).
- Functional assays for novel or uncertain variants, often performed in partnership with international collaborators.
Results are reviewed by multidisciplinary teams of immunologists, geneticists, and bioinformaticians. Variants of uncertain significance are discussed in national and international forums, with functional validation often proving decisive. Post-test genetic counseling addresses recurrence risks, cascade testing of family members, and reproductive options such as prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD).
Systemic and Policy Considerations
National insurance typically reimburses up to 80% of treatment costs, helping reduce long-term care burdens. However, coverage for genetic testing remains limited, leaving families reliant on NGOs or international research projects. Additional challenges include:
- Delayed or missed diagnosis, sometimes for years.
- Restricted access to immunoglobulin and other essential therapies, with periodic shortages and financial barriers.
- Unequal access to care, particularly for patients in underserved or rural areas.
- Psychosocial burdens, affecting education, careers, and family life.
- Navigating new therapies, requiring updated knowledge, equitable access, and regulatory support.
A major public health concern is the universal BCG vaccination administered at birth, which can cause life-threatening complications in undiagnosed infants with severe IEI. At present, Iran lacks a national newborn screening program (e.g., TREC/KREC), though pilot projects and advocacy initiatives are ongoing.
Research and Capacity Building
Iran has developed strong IEI research capacity, including:
- Establishment of national IEI patient registries
- University-led clinical and translational research programs
- International collaborations leading to the discovery of novel IEI-associated genes
Future Directions
Iran’s combination of strong clinical expertise, established infrastructure, and active research networks positions the country as a potential regional leader in IEI diagnosis and management. Closing the diagnostic and treatment gap will require:
- Expanding physician awareness and training.
- Broadening access to advanced genetic and functional testing nationwide.
- Strengthening national and international coordination in diagnosis, counseling, and research.
Advancing these priorities will not only improve outcomes for patients in Iran but also enable the country to contribute more substantially to global IEI research and innovation.
Report prepared by Roya Sherkat, M.D, Clinical Immunologist;
Director, Immunodeficiency Diseases Research Center & Association, Isfahan University of Medical Sciences
