Mapping Out Autoimmunity Control in Primary Immune Regulatory Disorders

There is a growing understanding of the clinical overlap between primary immune deficiency and autoimmunity. An atypical or treatment-refractory clinical presentation of autoimmunity may in fact signal an underlying congenital condition of primary immune dysregulation (an inborn error of immunity). Detailed profiling of the family history is critical in the diagnostic process and must not be limited to the occurrence of frequent or atypical infections, but additionally should include inquiries into chronic forms of autoimmunity, hyperinflammation, and malignancy. A genetic and a functional diagnostic approach are complementary and nonoverlapping methods of identifying and validating an inborn error of immunity. Extended immune phenotyping of both affected and unaffected family members may provide insight into disease mode of inheritance, penetrance, and secondary inherited or environmentally acquired modifiers. Clinical care of a family with an inborn error of immunity may require local and national expertise in addition to cross-disciplinary care from the disciplines of pediatrics and internal medicine. Physician communication across subspecialties as well as distinct medical institutes can facilitate the appropriate disclosure of genetic testing results toward their prompt incorporation into patient care. Targeted immunomodulation based directly on genetic and functional immune phenotyping has the potential to reduce unnecessary immunosuppression and provide more exacting therapeutic benefit to our patients.