P-1561. Autoantibodies to Interferon-γ and Susceptibility to Mycobacterial and other Opportunistic Intracellular Pathogens

TL;DR

The study shows that autoantibodies against interferon-γ are linked to severe infections from intracellular pathogens like mycobacteria.

Contribution

The novel finding is the association of elevated anti-IFNγ autoantibodies with susceptibility to opportunistic intracellular infections.

Findings

Patients with opportunistic infections had significantly higher anti-IFNγ autoantibody levels than healthy controls.

Disseminated non-tuberculous mycobacterial infection was the most common opportunistic infection in the study group.

Serum IL12p70 concentrations were significantly higher in patients with severe opportunistic infections.

Abstract

Autoantibodies against interferon-γ (IFN-γ) are increasingly associated with severe disseminated opportunistic infections. IFN-γ is a potent anti-bacterial and immunomodulatory cytokine playing a major role in controlling intracellular infections. Adult-onset immunodeficiency associated with life-threatening intracellular infections is characterized by the presence of anti-IFN-γ-autoantibodies (Abs).Table 1:Patient characteristicsTable 2:Comparison of serum anti-IFN gamma and IL12 p70 concentrations between opportunistic Infections, tuberculosis, and healthy control groups

Patient characteristics

Comparison of serum anti-IFN gamma and IL12 p70 concentrations between opportunistic Infections, tuberculosis, and healthy control groups

In this observational study, data and sera from 119 individuals with intracellular opportunistic infections and healthy controls were collected and analyzed. Anti-IFNγ-autoAbs and IL12p70 concentrations in serum were measured using enzyme-linked immunosorbent assay (ELISA). Median anti-IFNγ-autoAbs and serum IL12p70 levels were compared with healthy controls. Mann-Whitney U-test was used to compare group differences.Figure: 1Serum anti-IFN gamma and IL12 p70 concentrations among opportunistic infections, tuberculosis, and healthy control groups

Serum anti-IFN gamma and IL12 p70 concentrations among opportunistic infections, tuberculosis, and healthy control groups

119 patients were enrolled in three groups: 44 patients with unusual severe disseminated opportunistic intracellular infections (group 1); 41 patients with slowly resolving tuberculosis infection (group 2); and 34 healthy controls (group 3). Disseminated non-tuberculous mycobacterial infection was the most common opportunistic infection identified 18 (40.9%) in group 1, followed by cryptococcal infections 16 (36.4%) and disseminated histoplasmosis 6 (13.6%). Median concentration of anti-IFNγ-autoAbs in group 1 was 66.02 ng/ml (IQR, 52.19, 85.86) while in group 2 and group 3 were 65.46 ng/ml (IQR, 52.31, 86.03) and 44.77 ng/ml (IQR, 28.56, 69.93). Median duration of treatment in group 1 was 15 months (IQR, 12, 18) and in group 2 was 18 months (IQR, 15, 24).

Serum concentrations of anti-IFNγ-autoAbs in group 1 and 2 exceeded the median concentrations in healthy controls by two-fold (P=0.004). Serum IL12p70 concentrations was significantly higher in group 1 (P=0.006) while in group 2, it did not differ significantly (P=0.34) as compared to healthy controls. Relapse occurred among 3 (6.8%) patients in group 1 and 3 (6.8%) patients in group 1 succumbed during the study period.

Anticytokine autoantibodies may cause acquired susceptibility to infection and their detection impacts clinical management. Reinfection, relapse or persistent infections are common requiring close long-term surveillance.

All Authors: No reported disclosures

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