Minireview: Insights into anti-interferon-γ autoantibodies

Abstract

The association between the presence of anti-interferon-γ autoantibodies and the onset of immunodeficiency with intracellular infections has been clearly established. No standard regimen to control the production of these pathogenic autoantibodies, apart from antimicrobial therapy to eliminate infections, contributes to the medical burden of this syndrome, which sometimes has a fatal outcome. In this review, we summarize the findings on anti-interferon-γ autoantibodies to facilitate further research and to provide guidance for treatment strategies.

Disseminated Mycobacterium avium complex infection in a woman with anti-interferon-γ autoantibodies

“…Since the beginning of the millennium, several cases of disseminated infections with NTM in the presence of high titers of anti-IFN-γ autoantibodies have been described among HIV-negative patients [5] , [9] , [10] , [11] , [12] . The prevalence of this immunodeficiency, defined ‘anti-IFN-γ autoantibody-associated immunodeficiency syndrome’, is unknown and is probably underdiagnosed [2] , [4] . The syndrome is most often reported among midlife females of East Asian heritage [2] , [5] .…”

“…Yet, the patient was somewhat older in this case. The mechanisms and triggers of the disease are not clearly understood [4] , but the syndrome has been associated with HLA-DRB1 and HLA-DQB1 [13] , [14] , [15] . Moreover, molecular mimicry has been proposed as a potential mechanism of autoantibody production [16] .…”

“…As a matter of fact, the disease seemed to progress with dissemination of MAC outside the lungs. At the moment, the evidence about treatment of patients with anti-IFN-γ antibodies remains sparse and cure is rarely achieved [2] , [4] . Antimicrobial therapy is most often insufficient with slow remission or frequent relapses [19] .…”

“…Rituximab is the most studied immunomodulatory drug among patients with anti-IFN-γ autoantibody-associated immunodeficiency syndrome, and was considered during the course of disease, but was withheld, awaiting effect of antibiotics. Although evidence is still needed, rituximab appears to improve clinical outcomes by decreasing both titers and neutralizing capacity of the antibodies [2] , [3] , [4] . However, it is still unclear what the preferable drugs are and what the optimal strategy is, e.g., supporting the immune system and/or on inhibiting the synthesis of autoantibodies.…”

“…Mycobacterium avium complex (MAC) is a group of nontuberculous mycobacteria usually causing disease in individuals with immunodeficiency or structural lung disease [1] . Defects in the interleukin-12 (IL-12)/interferon-gamma (IFN-γ) pathway and autoantibodies against IFN-γ have been associated with severe NTM infections [2] , [3] , [4] , [5] and Salmonella infections and Herpesviridae reactivations have also been associated with these immunodeficiencies [2] , [3] , [4] , [5] .…”