Humoral Immune Dysregulation Defines High-Risk Cirrhotic Ascites
Klepper, A.; Zinter, M. S.; Roach, T.; Sidhu, S.; Berman, Z.; Dureja, I.; Dandekar, R.; Ganem, S.; Perlaza, K.; Castillo-Rojas, B.; Zorn, K.; Maher, J. J.; Baron, J. L.; Yocum, M.; Lai, A. R.; Lai, J.; DeRisi, J. L.
Show abstract
Fluid accumulates within serosal cavities in diverse disease states, where it creates biologically active and potentially pathologic niches. How these expanded microenvironments reflect and shape disease biology remains incompletely resolved. Here, we investigated human ascites fluid (n = 118), a hallmark of decompensated cirrhosis, to determine whether signatures of microbial exposure and local host response distinguish outcomes. Cirrhotic ascites was characterized by barrier remodeling, depletion of plasma cell-associated programs, and enrichment of oropharyngeal microbes. Surprisingly, detection of oropharyngeal microbes in ascites was not associated with adverse outcomes. Instead, the ascites of cirrhotic patients with poor outcomes was marked by profound plasma cell depletion and significantly reduced dimeric IgA, despite the presence of antigen-experienced B cells. Together, these findings identify local B cell dysregulation as a previously underappreciated component of cirrhosis-associated immune dysfunction. Impaired local humoral immunity, rather than microbial translocation alone, emerges as a feature of high-risk decompensated cirrhosis.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Early immune pathology and persistent dysregulation characterise severe COVID-19 93%
- Functional proteomic profiling links deficient DNA clearance to mortality in patients with severe COVID-19 pneumonia 93%
- Antibody responses against bacterial glycans affinity mature and diversify in germinal centers. 92%
Similar papers in this journal
Similar papers in this journal
- MTG16 (CBFA2T3) regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors 93%
- IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function 92%
- MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn's disease 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.