Characterization of Anti-Interferon-γ Antibodies in HIV-Negative Patients Infected With Disseminated Talaromyces marneffei and Cryptococcosis

Open Forum Infect Dis. 2019 Oct 11;6(10):ofz208. doi: 10.1093/ofid/ofz208. eCollection 2019 Oct.

Abstract

Background: Few reports of Talaromyces marneffei (TM) or cryptococcosis infections among HIV-negative patients with high-titeranti-IFN-γautoantibodies (nAIGAs) have been published. We investigated the clinical manifestations of patients with nAIGAs and TM infections.

Methods: HIV-negative adults (≥18 years) were enrolled if they haddisseminated TM infection (group 1; further divided into nAIGAs positive [group 1P] and negative [group 1N]); cryptococcosis(pulmonary cryptococcosis and/or cryptococcosis of the brain)(group 2); pulmonary tuberculosis (group 3); and healthy controls (group 4) with nAIGAs detected. Complete histories, physical examinations, and routine clinical laboratory tests were obtained at baseline.

Results: Overall, 88 participants were in the four groups (20,13,23, and 32 in groups 1 to 4, respectively). Significant differences occurred between groups with higher nAIGAs titers (P < 0.001), and higher total white-cell and absolute neutrophil counts (P < 0.001) in group1. Lungs (90.0%), lymph nodes (60.0%), skin (55.0%), and bones (50.0%) were most common sites of involvement. Significant differences in total white-cell and absolute neutrophil counts occurred between groups IP and 1N.Patients with recurrent TM infections, particularly group 1P, had higher initial nAIGA titer.

Conclusions: Patients with persistent infection who died tended to have positive initial nAIGA titer. It suggests that nAIGAs may play a critical role in the pathogenesis of TM infections, and may be associated with more severe, refractory infection.

Keywords: anti–interferon-γ antibodies; HIV-negative patients; cryptococcosis; talaromycosis.