TY - JOUR
T1 - Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation
AU - Berbers, Roos-Marijn
AU - Paganelli, Fernanda L
AU - van Montfrans, Joris M
AU - Ellerbroek, Pauline M
AU - Viveen, Marco C
AU - Rogers, Malbert R C
AU - Salomons, Moniek
AU - Schuurmans, Jaap
AU - van Stigt Thans, Martine
AU - Vanmaris, Remi M M
AU - Brosens, Lodewijk A A
AU - van der Wal, Maria Marlot
AU - Dalm, Virgil A S H
AU - van Hagen, P Martin
AU - van de Ven, Annick A J M
AU - Uh, Hae-Won
AU - van Wijk, Femke
AU - Willems, Rob J L
AU - Leavis, Helen L
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/1/16
Y1 - 2025/1/16
N2 - Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid. Results: Bacterial invasion of colonic crypts was observed in CVID (3/15) and X-linked agammaglobulinemia (XLA, 1/3), but not in healthy control (HC, 0/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (n = 42) compared to HC (n = 48), and similar results were seen in CVID with IgA deficiency (n = 40) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus Enterococcus, and in vitro studies confirmed the inflammatory potential of Enterococcus gallinarum and Enterococcus hirae in patient monocytes. Conclusions: This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid.
AB - Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid. Results: Bacterial invasion of colonic crypts was observed in CVID (3/15) and X-linked agammaglobulinemia (XLA, 1/3), but not in healthy control (HC, 0/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (n = 42) compared to HC (n = 48), and similar results were seen in CVID with IgA deficiency (n = 40) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus Enterococcus, and in vitro studies confirmed the inflammatory potential of Enterococcus gallinarum and Enterococcus hirae in patient monocytes. Conclusions: This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid.
KW - Common variable immunodeficiency (CVID)
KW - Gut microbiota
KW - Immune dysregulation
KW - Pathobionts
UR - http://www.scopus.com/inward/record.url?scp=85216048475&partnerID=8YFLogxK
U2 - 10.1186/s40168-024-01982-y
DO - 10.1186/s40168-024-01982-y
M3 - Article
C2 - 39819634
SN - 2049-2618
VL - 13
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 12
ER -