Objective:

To summarize clinical evidence for immune dysfunction in nucleotide excision repair (NER) disorders and discuss its implications for immunological assessment.

Approach:

• Clinical Evidence Review: The article reviews recent clinical and immunological studies that highlight immune abnormalities in NER disorders.
• Molecular Context: It interprets immune dysfunction in the context of global genome and transcription-coupled NER.

Key Findings:

• Immune dysfunction in NER disorders includes impaired vaccine responses, hypogammaglobulinemia, IgG subclass deficiency, altered B cell differentiation, CD4 lymphopenia, restricted T cell receptor repertoires, and defective dendritic cell maturation.
• Immune abnormalities are more prominent in specific molecular subgroups, particularly those involving transcription-associated NER defects.
• NER disorders have traditionally been viewed primarily in terms of dermatologic and neurologic manifestations, with immune dysfunction considered secondary.

Interpretation:

Recent findings indicate that immune dysfunction may be an underrecognized aspect of certain NER disorders, particularly those affecting transcription-associated NER functions.

Limitations:

• Systematic immunological assessment has been performed in only a limited number of patients and genotypes.
• The molecular heterogeneity of the NER pathway complicates the understanding of immune involvement.

Conclusion:

The article emphasizes the need for further research into the immune implications of NER disorders to improve clinical assessment and classification.