Study led by IGTP reveals correlation between tuberculosis lesion transcriptomics and patients’ clinical parameters

Researchers from the Experimental Tuberculosis Unit (UTE) at the Germans Trias i Pujol Research Institute (IGTP) and the Germans Trias i Pujol University Hospital have published a study in Nature Communications in which, for the first time, the transcriptomic profile of human tuberculosis lung lesions is correlated with clinical data from the same patients.

The study, led by Dr Cristina Vilaplana, applied RNAseq techniques to 44 fresh tissue samples from lesional and adjacent lung areas of patients with drug-sensitive and multidrug-resistant tuberculosis who underwent therapeutic surgery. The results show a clear separation between lesional and non-lesional tissue, with high expression of pro-inflammatory genes in the lesions. Weighted gene co-expression network analysis (WGCNA) identified 17 differential transcriptomic modules and revealed a gradient of immune response elements depending on their location within the lesion.

Although lesion transcriptomics had been studied previously, this is the first work to associate these molecular profiles with clinical indicators from the same patients. "Individuals with more severe forms of the disease present more inflamed lesions, while patients with better clinical outcomes show profiles compatible with tissue repair phases," explains Dr Cristina Vilaplana.

The researchers used two clinical surrogates: a validated respiratory quality of life questionnaire (SGRQ) and sputum culture conversion. "We confirmed that when a patient says they feel unwell, it is also reflected at the molecular level: their lesions show a stronger inflammatory response," adds Vilaplana. Furthermore, patients who take longer to achieve sputum culture conversion -a factor previously linked to worse prognosis- also show higher immune activation at the lesion site. "These data open the door to personalised strategies: if after two months the patient hasn't cleared the bacillus, we may need to adapt the treatment to modulate the inflammatory response and avoid a worse clinical outcome," she concludes.

The study, initiated in 2016, was made possible through collaboration with institutions including the NCTLD (Georgia), the Francis Crick Institute, Imperial College London, and other national and international biomedical centres. It was supported by funding from the Instituto de Salud Carlos III, the European Commission, AGAUR, SEPAR, Wellcome Trust, Medical Research Foundation, NIHR, NC3Rs, and two CIBER programmes: CIBERES and CIBEREHD.