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Humoral immune responses primed by the alteration of gut microbiota were associated with galactose-deficient IgA1 production in IgA nephropathy.
Gao, Li; Li, Huixian; Liu, Xiaoling; Li, Haiyun; Li, Peiqi; Lu, Wanhong; Xie, Xinfang; Lv, Jicheng; Jin, Jing.
Afiliación
  • Gao L; Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Li H; Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Liu X; Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Li H; MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Science, Lanzhou University, Lanzhou, China.
  • Li P; MOE Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
  • Lu W; Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Xie X; Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Lv J; Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Jin J; Renal Division, Peking University First Hospital; Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
Front Immunol ; 15: 1415026, 2024.
Article en En | MEDLINE | ID: mdl-39104521
ABSTRACT

Introduction:

Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN.

Methods:

By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified.

Results:

The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN.

Conclusion:

Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina A / Inmunidad Humoral / Microbioma Gastrointestinal / Galactosa / Glomerulonefritis por IGA Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina A / Inmunidad Humoral / Microbioma Gastrointestinal / Galactosa / Glomerulonefritis por IGA Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China