Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores

Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representi...

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Main Authors: Dana V. Rizk, Lea Novak, Stacy D. Hall, Zina Moldoveanu, Bruce A. Julian, Jan Novak, Mark Haas
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/12/23/7361
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author Dana V. Rizk
Lea Novak
Stacy D. Hall
Zina Moldoveanu
Bruce A. Julian
Jan Novak
Mark Haas
author_facet Dana V. Rizk
Lea Novak
Stacy D. Hall
Zina Moldoveanu
Bruce A. Julian
Jan Novak
Mark Haas
author_sort Dana V. Rizk
collection DOAJ
description Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy.
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spelling doaj.art-05fa26597da64650a0de7c3d4dfa7dd12023-12-08T15:19:37ZengMDPI AGJournal of Clinical Medicine2077-03832023-11-011223736110.3390/jcm12237361Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C ScoresDana V. Rizk0Lea Novak1Stacy D. Hall2Zina Moldoveanu3Bruce A. Julian4Jan Novak5Mark Haas6Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USARoutine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy.https://www.mdpi.com/2077-0383/12/23/7361IgA nephropathyIgANimmune complexeslight chainsconfocal microscopyMEST-C scores
spellingShingle Dana V. Rizk
Lea Novak
Stacy D. Hall
Zina Moldoveanu
Bruce A. Julian
Jan Novak
Mark Haas
Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
Journal of Clinical Medicine
IgA nephropathy
IgAN
immune complexes
light chains
confocal microscopy
MEST-C scores
title Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
title_full Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
title_fullStr Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
title_full_unstemmed Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
title_short Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores
title_sort colocalization of igg and iga heavy chains with kappa and lambda light chains in glomerular deposits of iga nephropathy patients using high resolution confocal microscopy and correlation with oxford mest c scores
topic IgA nephropathy
IgAN
immune complexes
light chains
confocal microscopy
MEST-C scores
url https://www.mdpi.com/2077-0383/12/23/7361
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