Humoral Immune Dysregulation Defines High-Risk Cirrhotic Ascites
- 1University of California, San Francisco
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.
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BibTeX
@misc{klepper2026humoral,
title = {{Humoral Immune Dysregulation Defines High-Risk Cirrhotic Ascites}},
author = {A. Klepper and M. S. Zinter and T. Roach and S. Sidhu and Z. Berman and I. Dureja and R. Dandekar and S. Ganem and K. Perlaza and B. Castillo-Rojas and K. Zorn and J. J. Maher and J. L. Baron and M. Yocum and A. R. Lai and J. Lai and J. L. DeRisi},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754574},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754574v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Humoral Immune Dysregulation Defines High-Risk Cirrhotic Ascites
AU - A. Klepper
AU - M. S. Zinter
AU - T. Roach
AU - S. Sidhu
AU - Z. Berman
AU - I. Dureja
AU - R. Dandekar
AU - S. Ganem
AU - K. Perlaza
AU - B. Castillo-Rojas
AU - K. Zorn
AU - J. J. Maher
AU - J. L. Baron
AU - M. Yocum
AU - A. R. Lai
AU - J. Lai
AU - J. L. DeRisi
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754574
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754574v1
AB - 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.
ER -