Granulomatous inflammation in inborn errors of immunity

Area of Science:

• Immunology
• Pathology
• Genetics

Background:

• Granulomas are inflammatory infiltrates comprising macrophages and T cells, forming a distinct three-dimensional structure.
• They can be triggered by infectious or non-infectious antigens and are frequently observed in patients with inborn errors of immunity (IEI).
• Conditions like chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID) commonly feature granulomas.

Purpose of the Study:

• To review infectious triggers of granulomas in IEI.
• To discuss IEI forms presenting with non-infectious granulomas.
• To explore diagnostic technologies and therapeutic approaches for granulomatous inflammation in IEI.

Main Methods:

• Literature review focusing on granulomas in IEI.
• Analysis of infectious and non-infectious etiologies.
• Discussion of deep sequencing applications in identifying granuloma triggers.
• Review of management and therapeutic options.

Main Results:

• Granulomas in IEI range from 1%-4% prevalence.
• Atypical presentations of infections like Mycobacteria and Coccidioides can indicate underlying immunodeficiency.
• Deep sequencing has identified novel antigens, including Rubella virus, in IEI granulomas.
• Granulomas in IEI are linked to substantial morbidity and mortality.

Conclusions:

• The heterogeneity of granuloma presentation in IEI complicates treatment strategies.
• Identifying triggers, whether infectious or non-infectious, is crucial for effective management.
• Advancements in sequencing technology aid in uncovering infectious causes of granulomas.
• Effective management requires a comprehensive approach addressing specific granuloma presentations in IEI.