What are some of the proposed mechanisms for autoimmunity found in PID disorders? What are some PID disorders with autoimmune manifestations?
Pathogenic mechanisms that have been proposed and are being studied include:
- • Defects in central and peripheral tolerance
- • Impairment of apoptosis of autoreactive T cells
- • Diminished T-regulatory cell (Treg) number and/or function. One important recent discovery is the recognition of the role of “checkpoint” regulatory molecules, such as CTLA4, that influence antigen recognition and development of Treg cells
- • Mutations in genes involved in signaling cascades which play a downregulatory role in inflammation
- • Persistent inflammation due to frequent, recurrent, or chronic infections, which results in cell death and a larger than usual burden of cellular debris, leading to decreased clearance of self-antigens and immune complexes.
