Tuberculosis (TB) is among the leading causes of death by infectious diseases. An epidemiological association between Mycobacterium tuberculosis infection and autoimmune diseases like rheumatoid arthritis (RA) has been reported but it remains unclear if there is a causal relationship, and if so, which molecular pathways and regulatory mechanisms contribute to it. Here we used a computational biology approach by global gene expression meta-analysis to identify candidate genes and pathways that may link TB and RA. Data were collected from public expression databases such as NCBI GEO. Studies were selected that analyzed mRNA-expression in whole blood or blood cell populations in human case control studies at comparable conditions. Six TB and RA datasets (41 active TB patients, 33 RA patients, and 67 healthy controls) were included in the downstream analysis. This approach allowed the identification of deregulated genes that had not been identified in the single analysis of TB or RA patients and that were co-regulated in TB and RA patients compared to healthy subjects. The genes encoding TLR5, TNFSF10/TRAIL, PPP1R16B/TIMAP, SIAH1, PIK3IP1, and IL17RA were among the genes that were most significantly deregulated in TB and RA. Pathway enrichment analysis revealed ‘T cell receptor signaling pathway’, ‘Toll-like receptor signaling pathway,’ and ‘virus defense related pathways’ among the pathways most strongly associated with both diseases. The identification of a common gene signature and pathways substantiates the observation of an epidemiological association of TB and RA and provides clues on the mechanistic basis of this association. Newly identified genes may be a basis for future functional and epidemiological studies.

Objectives: Infections of the ascitic fluid are serious conditions that require rapid diagnosis and treatment. Ascites is often accompanied by other critical pathologies such as gastrointestinal bleeding and bowel perforation, and infection increases the risk of mortality in intensive care patients. Owing to a relatively low success rate of conventional culture methods in identifying the responsible pathogens, new methods may be helpful to guide antimicrobial therapy and to refine empirical regimens. Here, we aim to assess outcomes and to identify responsible pathogens in ascitic fluid infections, in order to improve patients’ care and to guide empirical therapy. Methods: Between October 2019 and March 2021, we prospectively collected 50 ascitic fluid samples from ICU patients with suspected infection. Beside standard culture-based microbiology methods, excess fluid underwent DNA isolation and was analyzed by next- and third-generation sequencing (NGS) methods. Results: NGS-based methods had higher sensitivity in detecting additional pathogenic bacteria such as E. faecalis and Klebsiella in 33 out of 50 (66%) ascitic fluid samples compared with culture-based methods (26%). Anaerobic bacteria were especially identified by sequencing-based methods in 28 samples (56%), in comparison with only three samples in culture. Analysis of clinical data showed a correlation between sequencing results and various clinical parameters such as peritonitis and hospitalization outcomes. Conclusions: Our results show that, in ascitic fluid infections, NGS-based methods have a higher sensitivity for the identification of clinically relevant pathogens than standard microbiological culture diagnostics, especially in detecting hard-to-culture anaerobic bacteria. Patients with such infections may benefit from the use of NGS methods by the possibility of earlier and better targeted antimicrobial therapy, which has the potential to lower the high morbidity and mortality in critically ill patients with ascitic bacterial infection.