Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract

Jingyi Li; Jingyi Li; Jingyi Li; Jingyi Li; Jingyi Li; Yaping Dong; Yaping Dong; Yaping Dong; Yaping Dong; Yaping Dong; Feifei Chen; Feifei Chen; Feifei Chen; Feifei Chen; Feifei Chen; Hongyu Yang; Hongyu Yang; Hongyu Yang; Hongyu Yang; Hongyu Yang; Pei Chen; Pei Chen; Pei Chen; Pei Chen; Pei Chen; Hongyu Li; Hongyu Li; Hongyu Li; Hongyu Li; Hongyu Li; Sufang Shi; Sufang Shi; Sufang Shi; Sufang Shi; Sufang Shi; Xujie Zhou; Xujie Zhou; Xujie Zhou; Xujie Zhou; Xujie Zhou; Li Zhu; Li Zhu; Li Zhu; Li Zhu; Li Zhu; Yuemiao Zhang; Yuemiao Zhang; Yuemiao Zhang; Yuemiao Zhang; Yuemiao Zhang; Lijun Liu; Lijun Liu; Lijun Liu; Lijun Liu; Lijun Liu; Xinfang Xie; Feng Yu; Jing Jin; Jicheng Lv; Jicheng Lv; Jicheng Lv; Jicheng Lv; Jicheng Lv; Hong Zhang; Hong Zhang; Hong Zhang; Hong Zhang; Hong Zhang

doi:10.3389/fimmu.2024.1368322

Frontiers in Immunology (Mar 2024)

Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract

Jingyi Li,
Jingyi Li,
Jingyi Li,
Jingyi Li,
Jingyi Li,
Yaping Dong,
Yaping Dong,
Yaping Dong,
Yaping Dong,
Yaping Dong,
Feifei Chen,
Feifei Chen,
Feifei Chen,
Feifei Chen,
Feifei Chen,
Hongyu Yang,
Hongyu Yang,
Hongyu Yang,
Hongyu Yang,
Hongyu Yang,
Pei Chen,
Pei Chen,
Pei Chen,
Pei Chen,
Pei Chen,
Hongyu Li,
Hongyu Li,
Hongyu Li,
Hongyu Li,
Hongyu Li,
Sufang Shi,
Sufang Shi,
Sufang Shi,
Sufang Shi,
Sufang Shi,
Xujie Zhou,
Xujie Zhou,
Xujie Zhou,
Xujie Zhou,
Xujie Zhou,
Li Zhu,
Li Zhu,
Li Zhu,
Li Zhu,
Li Zhu,
Yuemiao Zhang,
Yuemiao Zhang,
Yuemiao Zhang,
Yuemiao Zhang,
Yuemiao Zhang,
Lijun Liu,
Lijun Liu,
Lijun Liu,
Lijun Liu,
Lijun Liu,
Xinfang Xie,
Feng Yu,
Jing Jin,
Jicheng Lv,
Jicheng Lv,
Jicheng Lv,
Jicheng Lv,
Jicheng Lv,
Hong Zhang,
Hong Zhang,
Hong Zhang,
Hong Zhang,
Hong Zhang

Affiliations

Jingyi Li: Renal Division, Peking University First Hospital, Beijing, China
Jingyi Li: Institute of Nephrology, Peking University, Beijing, China
Jingyi Li: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Jingyi Li: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Jingyi Li: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Yaping Dong: Renal Division, Peking University First Hospital, Beijing, China
Yaping Dong: Institute of Nephrology, Peking University, Beijing, China
Yaping Dong: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Yaping Dong: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Yaping Dong: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Feifei Chen: Renal Division, Peking University First Hospital, Beijing, China
Feifei Chen: Institute of Nephrology, Peking University, Beijing, China
Feifei Chen: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Feifei Chen: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Feifei Chen: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Hongyu Yang: Renal Division, Peking University First Hospital, Beijing, China
Hongyu Yang: Institute of Nephrology, Peking University, Beijing, China
Hongyu Yang: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Hongyu Yang: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Hongyu Yang: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Pei Chen: Renal Division, Peking University First Hospital, Beijing, China
Pei Chen: Institute of Nephrology, Peking University, Beijing, China
Pei Chen: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Pei Chen: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Pei Chen: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Hongyu Li: Renal Division, Peking University First Hospital, Beijing, China
Hongyu Li: Institute of Nephrology, Peking University, Beijing, China
Hongyu Li: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Hongyu Li: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Hongyu Li: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Sufang Shi: Renal Division, Peking University First Hospital, Beijing, China
Sufang Shi: Institute of Nephrology, Peking University, Beijing, China
Sufang Shi: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Sufang Shi: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Sufang Shi: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Xujie Zhou: Renal Division, Peking University First Hospital, Beijing, China
Xujie Zhou: Institute of Nephrology, Peking University, Beijing, China
Xujie Zhou: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Xujie Zhou: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Xujie Zhou: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Li Zhu: Renal Division, Peking University First Hospital, Beijing, China
Li Zhu: Institute of Nephrology, Peking University, Beijing, China
Li Zhu: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Li Zhu: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Li Zhu: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Yuemiao Zhang: Renal Division, Peking University First Hospital, Beijing, China
Yuemiao Zhang: Institute of Nephrology, Peking University, Beijing, China
Yuemiao Zhang: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Yuemiao Zhang: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Yuemiao Zhang: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Lijun Liu: Renal Division, Peking University First Hospital, Beijing, China
Lijun Liu: Institute of Nephrology, Peking University, Beijing, China
Lijun Liu: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Lijun Liu: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Lijun Liu: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Xinfang Xie: Department of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
Feng Yu: Department of Nephrology, Peking University International Hospital, Beijing, China
Jing Jin: Northwestern University Feinberg School of Medicine, Division of Nephrology, Chicago, IL, United States
Jicheng Lv: Renal Division, Peking University First Hospital, Beijing, China
Jicheng Lv: Institute of Nephrology, Peking University, Beijing, China
Jicheng Lv: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Jicheng Lv: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Jicheng Lv: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
Hong Zhang: Renal Division, Peking University First Hospital, Beijing, China
Hong Zhang: Institute of Nephrology, Peking University, Beijing, China
Hong Zhang: Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
Hong Zhang: Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
Hong Zhang: State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China

DOI: https://doi.org/10.3389/fimmu.2024.1368322
Journal volume & issue: Vol. 15

Abstract

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IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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