Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection

Darragh Duffy (1) , Elisa Nemes (2) , Alba Llibre (1) , Vincent Rouilly (3) , Munyaradzi Musvosvi (2) , Nikaïa Smith (1) , Elizabeth Filander (2) , Hadn Africa (2) , Simbarashe Mabwe (2) , Lungisa Jaxa (2) , Bruno Charbit (4) , Humphrey Mulenga (2) , Consortium Milieu Intérieur , Michele Tameris (2) , Gerhard Walzl (5) , Stephanus Malherbe (5) , Stephanie Thomas (1) , Mark Hatherill (2) , Nicole Bilek (2) , Thomas J Scriba (2) , Matthew L. Albert (6)

1 Immunobiologie des Cellules dendritiques
2 University of Cape Town
3 Datactix
4 CRT - Centre de Recherche Translationnelle - Center for Translational Science
5 Stellenbosch University
6 Insitro [San Francisco]

Background Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem. Clinical challenges include the lack of a blood-based test for active disease. Current blood-based tests, such as QuantiFERON (QFT) do not distinguish active TB disease from asymptomatic Mtb infection. Methods We hypothesized that TruCulture, an immunomonitoring method for whole blood stimulation, could discriminate active disease from latent Mtb infection (LTBI). We stimulated whole blood from active TB patients and compared to LTBI donors. Mtb- specific antigens and live bacillus Calmette-Guerin (BCG) were used as stimuli, with direct comparison to QFT. Protein analyses were performed using conventional and digital ELISA, as well as Luminex. Results TruCulture showed discrimination of active TB cases from LTBI (p < 0.0001 AUC = 0.81) as compared to QFT (p = 0.45 AUC = 0.56), based on an IFNγ readout after Mtb antigen stimulation. This result was replicated in an independent cohort (AUC = 0.89). In exploratory analyses, TB stratification could be further improved by the Mtb Ag/BCG IFNγ ratio (p < 0.0001 AUC = 0.91). Finally, the combination of digital ELISA and transcriptional analysis showed that LTBI donors with high IFNγ clustered with TB patients, suggesting the possibility to identify sub-clinical disease. Conclusions TruCulture offers a next-generation solution for whole blood stimulation and immunomonitoring with the possibility to discriminate active and latent infection.

Mots clés: Immune profiling; Patient stratification; Tuberculosis; biomarkers; cytokines

Domaines: Immunologie

Darragh Duffy, Elisa Nemes, Alba Llibre, Vincent Rouilly, Munyaradzi Musvosvi, et al.. Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection. Clinical Infectious Diseases, 2020, ⟨10.1093/cid/ciaa1562⟩. ⟨pasteur-03036505⟩