Characterization of CD177-reactive iso- and auto-antibodies

Area of Science:

• Immunology
• Hematology
• Serology

Background:

• CD177 is a neutrophil surface protein crucial for proteinase 3 (PR3) expression.
• Antibodies targeting CD177 include isoantibodies (in CD177-null individuals), autoantibodies (in autoimmune neutropenia), and antineutrophil cytoplasmic antibodies.

Purpose of the Study:

• To compare the binding characteristics of CD177 autoantibodies and isoantibodies.
• To optimize the detection of these antibodies in neutrophil serology.

Main Methods:

• Studied reactivity of iso- and auto-antibodies against CD177 using granulocytes, native CD177/PR3 complex, and recombinant CD177 or PR3.
• Utilized monoclonal antibodies (moabs) 7D8 and MEM166 to differentiate antibody binding.

Main Results:

• All antibodies reacted with CD177/PR3 immobilized by moab 7D8.
• Seventy-five percent of autoantibodies, but no isoantibodies, failed to react with CD177/PR3 immobilized by moab MEM166.
• Most autoantibodies did not bind recombinant CD177, unlike most isoantibodies.

Conclusions:

• CD177 iso- and auto-antibodies target different epitopes.
• Isoantibodies primarily bind CD177, whereas autoantibodies recognize a native CD177/PR3 epitope.
• Moab MEM166 binding suggests it targets an epitope crucial for autoantibody detection, aiding diagnostic strategy development.