Clinical Report: Immune System Impairment in Nucleotide Excision Repair Disorders

Background

Nucleotide excision repair (NER) is crucial for maintaining genomic stability by repairing DNA lesions. Inherited defects in NER genes lead to rare disorders that are primarily characterized by photosensitivity and neurodevelopmental issues. However, immune dysfunction has been overlooked, despite evidence suggesting it plays a significant role in the morbidity of these patients.

Data Highlights

Recent studies have reported various immune abnormalities in NER disorders, including:

Key Findings

• Impaired vaccine responses in patients with NER disorders.
• Hypogammaglobulinemia and IgG subclass deficiencies observed in some patients.
• Altered B cell differentiation and CD4 lymphopenia reported.
• Restricted T cell receptor repertoires noted in specific genetic subgroups.
• Defective dendritic cell maturation identified as a significant concern.

Clinical Implications

Clinicians should consider the potential for immune dysfunction in patients with NER disorders, particularly during infections or vaccinations.

Conclusion

The recognition of immune dysfunction as a significant aspect of NER disorders may lead to improved clinical management and outcomes for affected patients.

Related Resources & Content

1. Frontiers in Immunology, 2026 -- Immune dysfunction in nucleotide excision repair disorders: an underrecognized clinical phenotype with relevance for inborn errors of immunity
2. Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee - PMC
3. Frontiers in Immunology — A multidisciplinary RNA-guided approach to complement genomic analysis of unsolved patients with an inborn error of immunity
4. Frontiers in Immunology — De novo NFKBIA variants within the N-terminal hotspot: consistent immunophenotype and divergent clinical presentations
5. Bone Marrow Transplantation — Is Assessing Gene Polymorphisms Useful for Personalizing Treatment in HSCT Patients?
6. Blood Cancer Journal — Inherited Genetic Variants Linked to Diffuse Large B-Cell Lymphoma Risk
7. Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee - PMC
8. Frontiers | Immune dysfunction in nucleotide excision repair disorders: an underrecognized clinical phenotype with relevance for inborn errors of immunity
9. 2025 Inborn errors of immunity practice parameter: Guidance from the Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma & Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI) and the Clinical Immunology Society (CIS) - PubMed