IL12RB1 Deficiency Appearing in North America: Expanding the Clinical Phenotypes

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Interleukin-12 receptor beta 1 (IL12RB1) deficiency is a primary immunodeficiency.
• It is the most frequent genetic cause of Mendelian susceptibility to mycobacterial disease worldwide.
• Disseminated Bacillus Calmette-Guérin (BCG) infection is a common presentation in endemic regions.

Purpose of the Study:

• To describe the clinical presentations of IL12RB1 deficiency.
• To highlight geographic variations in disease manifestation.
• To emphasize unrecognized presentations in North America.

Main Methods:

• Review of clinical data from patients with IL12RB1 deficiency.
• Analysis of infection types and outcomes.
• Comparison of presentations between BCG-vaccinated and unvaccinated populations.

Main Results:

• IL12RB1 deficiency commonly presents as disseminated BCG infection in BCG-vaccinated regions.
• In North America, where BCG is not routinely administered, patients present with diverse bacterial and fungal infections.
• These findings suggest distinct, potentially overlooked, clinical phenotypes of IL12RB1 deficiency in specific geographic areas.

Conclusions:

• The presentation of IL12RB1 deficiency is influenced by BCG vaccination status and geographic location.
• Recognizing varied clinical manifestations is crucial for timely diagnosis and management of IL12RB1 deficiency.
• Further research is needed to fully understand the spectrum of infections associated with IL12RB1 deficiency in different populations.