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IgM exacerbates glomerular disease progression in complement induced glomerulopathy

While glomerular IgM deposition occurs in a variety of glomerular diseases the mechanism of deposition and its clinical significance remain controversial. Some have theorized IgM becomes passively trapped in areas of glomerulosclerosis. However, recent studies found that IgM specifically binds damag...

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Autores principales: Panzer, Sarah E., Laskowski, Jennifer, Renner, Brandon, Kulik, Liudmila, Ljubanovic, Danica, Huber, Kendra M., Zhong, Weixiong, Pickering, Matthew C., Holers, V. Michael, Thurman, Joshua M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556608/
https://www.ncbi.nlm.nih.gov/pubmed/25945405
http://dx.doi.org/10.1038/ki.2015.120
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author Panzer, Sarah E.
Laskowski, Jennifer
Renner, Brandon
Kulik, Liudmila
Ljubanovic, Danica
Huber, Kendra M.
Zhong, Weixiong
Pickering, Matthew C.
Holers, V. Michael
Thurman, Joshua M.
author_facet Panzer, Sarah E.
Laskowski, Jennifer
Renner, Brandon
Kulik, Liudmila
Ljubanovic, Danica
Huber, Kendra M.
Zhong, Weixiong
Pickering, Matthew C.
Holers, V. Michael
Thurman, Joshua M.
author_sort Panzer, Sarah E.
collection PubMed
description While glomerular IgM deposition occurs in a variety of glomerular diseases the mechanism of deposition and its clinical significance remain controversial. Some have theorized IgM becomes passively trapped in areas of glomerulosclerosis. However, recent studies found that IgM specifically binds damaged glomeruli. Therefore, we tested whether natural IgM binds to neo-epitopes exposed after insults to the glomerulus and exacerbate disease in mice deficient in the complement regulatory protein factor H; a model of non-sclerotic and nonimmune-complex glomerular disease. Immunofluorescence microscopy demonstrated mesangial and capillary loop deposition of IgM while ultrastructural analysis found IgM deposition on endothelial cells and subendothelial areas. Factor H deficient mice lacking B cells were protected from renal damage, as evidenced by milder histologic lesions on light and electron microscopy. IgM, but not IgG, from wild-type mice bound to cultured murine mesangial cells. Furthermore, injection of purified IgM into mice lacking B cells bound within the glomeruli and induced proteinuria. A monoclonal natural IgM recognizing phospholipids also bound to glomeruli in vivo and induced albuminuria. Thus, our results indicate specific IgM antibodies bind to glomerular epitopes and that IgM contributes to the progression of glomerular damage in this mouse model of non-sclerotic glomerular disease.
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spelling pubmed-45566082016-03-01 IgM exacerbates glomerular disease progression in complement induced glomerulopathy Panzer, Sarah E. Laskowski, Jennifer Renner, Brandon Kulik, Liudmila Ljubanovic, Danica Huber, Kendra M. Zhong, Weixiong Pickering, Matthew C. Holers, V. Michael Thurman, Joshua M. Kidney Int Article While glomerular IgM deposition occurs in a variety of glomerular diseases the mechanism of deposition and its clinical significance remain controversial. Some have theorized IgM becomes passively trapped in areas of glomerulosclerosis. However, recent studies found that IgM specifically binds damaged glomeruli. Therefore, we tested whether natural IgM binds to neo-epitopes exposed after insults to the glomerulus and exacerbate disease in mice deficient in the complement regulatory protein factor H; a model of non-sclerotic and nonimmune-complex glomerular disease. Immunofluorescence microscopy demonstrated mesangial and capillary loop deposition of IgM while ultrastructural analysis found IgM deposition on endothelial cells and subendothelial areas. Factor H deficient mice lacking B cells were protected from renal damage, as evidenced by milder histologic lesions on light and electron microscopy. IgM, but not IgG, from wild-type mice bound to cultured murine mesangial cells. Furthermore, injection of purified IgM into mice lacking B cells bound within the glomeruli and induced proteinuria. A monoclonal natural IgM recognizing phospholipids also bound to glomeruli in vivo and induced albuminuria. Thus, our results indicate specific IgM antibodies bind to glomerular epitopes and that IgM contributes to the progression of glomerular damage in this mouse model of non-sclerotic glomerular disease. 2015-05-06 2015-09 /pmc/articles/PMC4556608/ /pubmed/25945405 http://dx.doi.org/10.1038/ki.2015.120 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Panzer, Sarah E.
Laskowski, Jennifer
Renner, Brandon
Kulik, Liudmila
Ljubanovic, Danica
Huber, Kendra M.
Zhong, Weixiong
Pickering, Matthew C.
Holers, V. Michael
Thurman, Joshua M.
IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title_full IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title_fullStr IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title_full_unstemmed IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title_short IgM exacerbates glomerular disease progression in complement induced glomerulopathy
title_sort igm exacerbates glomerular disease progression in complement induced glomerulopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556608/
https://www.ncbi.nlm.nih.gov/pubmed/25945405
http://dx.doi.org/10.1038/ki.2015.120
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