Background/Purpose: Interferon gamma (IFN-G) is critical cytokine for defense against intracellular pathogens; it is also involved in the pathogenesis of systemic lupus erythematosus (SLE). The IFN-G release assay (IGRA) estimates probability of latent tuberculosis (TB) infection (LTBI) based on whole-blood IFN-G release upon exposure to TB antigen, mitogen (IGRA-MT) or no stimulation (IGRA-NL). We previously observed that elevated IGRA-NL values (representing spontaneous IFN-G release, SIR) are associated with a limited set of diagnoses, including LTBI and SLE. Here, we examine the clinical and immunologic correlates of SIR in a cohort of SLE patients undergoing IGRA testing. We hypothesize that SIR is associated with active SLE and select disease manifestations.

Methods: We queried a clinical data repository (2010–2016) from a U.S. academic medical center for subjects with a diagnosis of SLE, a positive ANA and at least one IGRA result (n=167). SLE classification by SLICC criteria was confirmed by chart review (n=99). Of these 99, 53 had sufficient data to calculate a complete SELENA-SLEDAI (SLEDAI) score at the time of IGRA testing. We then assessed relationships between IGRA-NL, IGRA-NL/MT ratios, SLEDAI and related clinical/immunologic variables using univariate (Fisher’s Exact, Kruskal-Wallis, Mann Whitney tests) and multivariate (linear regression) analyses.

Results: The cohort of 99 patients was 85% female, 71% non-white, with a median (range) age of 36 years (18–84) and disease duration of 3.9 years (0–39). Median (range) for SLEDAI (n = 53) was 12 (0–33). Compared to subjects without SLEDAI scores, subjects with SLEDAI scores had significantly shorter disease duration and higher IGRA-NL/MT ratios. Linear regression analysis revealed a significant positive association between IGRA-NL/MT ratios and SLEDAI (r = 0.53, p < 0.0001) that was stronger than that of IGRA-NL (r = 0.21, p = 0.0616) or anti-dsDNA (r = 0.32, p = 0.0107). The linear association between IGRA-NL/MT and SLEDAI remained significant (p = 0.031) after controlling for all non-SLEDAI variables significantly associated with upper-half IGRA-NL/MT ratios (history of APLA/lupus inhibitor, low complement, Coomb’s positivity, current prednisone 5-20 mg/d, current/past hydroxychloroquine use). SLEDAI features positively associated with upper-half IGRA-NL/MT were proteinuria (p = 0.0028), rash (p=0.0024), low complement (p=0.0394) and fever (p=0.0030). Using a 50^th percentile cutoff, IGRA-NL/MT could predict active disease (SLEDAI > 6) with a sensitivity of 77.5% and a specificity of 61.5% (p=0.0128), which was superior to either anti-dsDNA or IGRA-NL (neither statistically significant).

Conclusion: In our cohort of SLE patients undergoing IGRA testing, IGRA-NL/MT ratios correlated with and predicted active disease better than either anti-dsDNA or IGRA-NL. Correlation between IGRA-NL/MT and select disease features supports a pathogenic role for IFN-G activation in renal, dermatologic and systemic manifestations of SLE. Thus, the IGRA test may represent a readily available assay with unique biomarker potential in SLE.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-interferon-gamma-release-assay-is-a-novel-predictor-of-disease-activity-in-systemic-lupus-erythematosus/