Characterization of anti-interferon-gamma antibodies in HIV-negative immunodeficient patients infected with unusual intracellular microorganisms

A major characteristic of immunodeficiency associated with life-threatening intracellular infection in adults is the presence of anti-interferon-gamma antibodies. Although little is known about the mechanism underlying this syndrome, it is believed that the antibodies inhibit the activity of downstream signaling pathway of interferon-gamma. In this study, the characteristics of these antibodies in patients who presented, or have a history of, intracellular infection and were positive to anti-interferon-gamma antibodies were investigated. The antibodies exhibited mainly the IgG1 and the IgG4 subtypes and recognized the C-terminal of the interferon-gamma linear epitope containing the KRKR motif, which is required for the biological activity of interferon-gamma. The antibodies bound to recombinant interferon-gamma with significantly lower avidity than antibodies to a recall antigen, tetanus toxoid, suggesting that the antibodies might have not undergone affinity maturation. The data from this study may provide fundamental information to better understand the properties of anti-interferon-gamma antibodies, which can be useful for future studies.