An interferon-gamma release assay as a novel biomarker in systemic lupus erythematosus

Rheumatology (Oxford). 2020 Nov 1;59(11):3479-3487. doi: 10.1093/rheumatology/keaa161.


Objective: The mycobacterium tuberculosis (TB) IFN-γ release assay (TB-IGRA) assesses peripheral blood cell release of IFN-γ upon ex vivo exposure to mitogen (IGRA-MT), TB antigen or a negative/nil control (IGRA-NL); IGRA-NL is a measure of spontaneous IFN-γ release (SIR). Here, we investigate the diagnostic associations of elevated SIR and the potential use of IGRA-NL as a novel biomarker in SLE.

Methods: We analysed diagnostic code frequencies among 11 823 individuals undergoing TB-IGRA testing between 2010 and 2015 in a large urban US health-care system. To study the relationship between IGRA-NL and SLE, we identified 99 individuals with SLE and TB-IGRA test results then assessed correlations between IGRA-NL, normalized IGRA-NL (the quotient of IGRA-NL/IGRA-MT), disease manifestations and disease activity.

Results: We identified a discovery cohort of 108 individuals with elevated SIR (>5 S.d. above median) that was significantly enriched for a limited set of diagnoses, including SLE, TB infection, haemophagocytic lymphohistiocytosis and HIV infection. In SLE patients undergoing TB-IGRA testing, normalized IGRA-NL correlated better with disease activity than did anti-dsDNA or complement levels. This relationship appeared to reflect interactions between normalized IGRA-NL and the presence of acute skin disease, hypocomplementemia, fever and thrombocytopenia.

Conclusion: Elevated SIR appears to be associated with a limited number of disease processes, including SLE. The diagnostic utility of SIR remains to be determined. IFN-γ activation, as measured by the TB-IGRA test, may offer a readily available tool for assessing disease activity in patients with SLE.

Keywords: biomarkers; cross-sectional studies; cytokines; interferon-gamma; systemic lupus erythematosus.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis / physiopathology
  • Autoantibodies / immunology*
  • Complement System Proteins / immunology
  • Female
  • Fever / physiopathology
  • HIV Infections / immunology
  • Humans
  • Interferon-gamma / immunology*
  • Interferon-gamma Release Tests*
  • Leukopenia / physiopathology
  • Lupus Erythematosus, Cutaneous / immunology
  • Lupus Erythematosus, Cutaneous / physiopathology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Male
  • Middle Aged
  • Serositis / physiopathology
  • Thrombocytopenia / physiopathology
  • Tuberculosis / immunology
  • Young Adult


  • Autoantibodies
  • Interferon-gamma
  • Complement System Proteins