Kidney international · 2026
Characterization of IgA, IgA immune complexes and complement depositions in IgA nephropathy using laser microdissection and mass spectrometry.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Cara Anila, Singh Raman Deep, Berti Gian Marco, Vargas-Brochero Maria J F, Juanet Cristián, Majado Cristina Garcia, Russo Ilario, Laxamana Trisha, Madden Benjamin, Theis Jason D, Pereira Palma Lilian Monteiro, Nasr Samih H, Bu Lihong, Nath Karl A, Fervenza Fernando C, Sethi Sanjeev
Аннотация
INTRODUCTION: IgA nephropathy is characterized by accumulation of mesangial IgA immune complexes. These IgA immune complexes result in glomerular inflammation and subsequent sclerosis. Glomerular inflammation is mediated in part by activation of the complement pathway by these immune complexes.
METHODS: In this study of 22 cases of IgA nephropathy, using laser microdissection and mass spectrometry (LMD/MS), we characterized both IgA and complement deposits.
RESULTS: LMD/MS detected abundant IgA1 but also IgA2; detected in 100% and 82% of cases, respectively. Furthermore, J chains, that link IgA monomers to form dimeric IgA on mucosal surfaces, was detected in 91% of cases, while the polymeric Ig receptor found in secretory IgA was found in only 9% of the cases. IgG1 was the dominant IgG subclass and was detected in 100% of cases. IgG subclass staining and confocal immunofluorescence microscopy confirmed the IgG1 subclass and colocalization of IgG1 with IgA1 and IgA2.Evaluation of the complement pathways revealed abundant C3, C9, C5, C6, C7 and C8 with lesser amounts of C4 indicating activation of predominantly the alternative and terminal pathways of complement. LMD/MS also detected abundant complement regulating proteins including CFH, CFHR1, CFHR2 and CFHR5, CD59, and smaller amounts of CFB, indicating active regulation of the complement pathways. Although it did not reach statistical significance, high counts of C3, C5 and C9 were present in lesions with endocapillary hypercellularity/crescentic lesions. High counts of complement regulating proteins, particularly CFHR5, were also present in active lesions. C3 sequence coverage data showed the majority of amino acids detected belong to C3dg along with smaller amounts of C3c.
CONCLUSION: Our data shows that the IgA immune complexes are composed of mucosal-derived dimeric IgA1/IgA2 and IgG1. The majority of complement proteins detected are components of the alternative and terminal complement pathway.
METHODS: In this study of 22 cases of IgA nephropathy, using laser microdissection and mass spectrometry (LMD/MS), we characterized both IgA and complement deposits.
RESULTS: LMD/MS detected abundant IgA1 but also IgA2; detected in 100% and 82% of cases, respectively. Furthermore, J chains, that link IgA monomers to form dimeric IgA on mucosal surfaces, was detected in 91% of cases, while the polymeric Ig receptor found in secretory IgA was found in only 9% of the cases. IgG1 was the dominant IgG subclass and was detected in 100% of cases. IgG subclass staining and confocal immunofluorescence microscopy confirmed the IgG1 subclass and colocalization of IgG1 with IgA1 and IgA2.Evaluation of the complement pathways revealed abundant C3, C9, C5, C6, C7 and C8 with lesser amounts of C4 indicating activation of predominantly the alternative and terminal pathways of complement. LMD/MS also detected abundant complement regulating proteins including CFH, CFHR1, CFHR2 and CFHR5, CD59, and smaller amounts of CFB, indicating active regulation of the complement pathways. Although it did not reach statistical significance, high counts of C3, C5 and C9 were present in lesions with endocapillary hypercellularity/crescentic lesions. High counts of complement regulating proteins, particularly CFHR5, were also present in active lesions. C3 sequence coverage data showed the majority of amino acids detected belong to C3dg along with smaller amounts of C3c.
CONCLUSION: Our data shows that the IgA immune complexes are composed of mucosal-derived dimeric IgA1/IgA2 and IgG1. The majority of complement proteins detected are components of the alternative and terminal complement pathway.