Myeloperoxidase (MPO)-specific CD4+ T cells contribute to MPO-anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis

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Abstract

Autoimmunity to the neutrophil enzyme myeloperoxidase (MPO) is an important cause of rapidly progressive glomerulonephritis, but the relative roles of MPO-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and autoreactive effector MPO-specific CD4+ T cells are unclear. We confirmed that passive transfer of murine MPO-ANCA to agammaglobulinemic muMT mice immunized with OVA induces glomerular injury with capillary wall thickening, fibrinoid necrosis, mesangial cell proliferation, and periglomerular cell infiltration. Preimmunization of muMT mice with MPO induced MPO-specific CD4+ T cells and significantly enhanced renal injury after MPO-ANCA transfer. CD4+ T cell depletion prevented this augmentation of injury, confirming the importance of effector T cells in the development of MPO-ANCA associated glomerulonephritis. Therefore, MPO-ANCA can induce glomerulonephritis through both direct humoral mechanisms (recruitment of neutrophils and deposition of MPO) and indirectly by initiating MPO deposition in glomeruli, thereby directing effector CD4+ T cell mediated injury. To confirm and support this data, we transferred T cells from MPO-immunized Mpo-/-muMT mice into Rag1-/- mice (control mice received ovalbumin specific T cells) and triggered injury by passive MPO-ANCA. Renal injury was significantly greater in mice transferred with T cells from MPO-immunized mice. These current studies demonstrate that MPO-ANCA induces injury via both humoral and cell mediated immune mechanisms.
Original languageEnglish
Pages (from-to)21 - 27
Number of pages7
JournalCellular Immunology
Volume282
Issue number1
DOIs
Publication statusPublished - 2013

Cite this

@article{1860e5175f3a49238e959baa996f523b,
title = "Myeloperoxidase (MPO)-specific CD4+ T cells contribute to MPO-anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis",
abstract = "Autoimmunity to the neutrophil enzyme myeloperoxidase (MPO) is an important cause of rapidly progressive glomerulonephritis, but the relative roles of MPO-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and autoreactive effector MPO-specific CD4+ T cells are unclear. We confirmed that passive transfer of murine MPO-ANCA to agammaglobulinemic muMT mice immunized with OVA induces glomerular injury with capillary wall thickening, fibrinoid necrosis, mesangial cell proliferation, and periglomerular cell infiltration. Preimmunization of muMT mice with MPO induced MPO-specific CD4+ T cells and significantly enhanced renal injury after MPO-ANCA transfer. CD4+ T cell depletion prevented this augmentation of injury, confirming the importance of effector T cells in the development of MPO-ANCA associated glomerulonephritis. Therefore, MPO-ANCA can induce glomerulonephritis through both direct humoral mechanisms (recruitment of neutrophils and deposition of MPO) and indirectly by initiating MPO deposition in glomeruli, thereby directing effector CD4+ T cell mediated injury. To confirm and support this data, we transferred T cells from MPO-immunized Mpo-/-muMT mice into Rag1-/- mice (control mice received ovalbumin specific T cells) and triggered injury by passive MPO-ANCA. Renal injury was significantly greater in mice transferred with T cells from MPO-immunized mice. These current studies demonstrate that MPO-ANCA induces injury via both humoral and cell mediated immune mechanisms.",
author = "Gan, {Poh Yi} and Holdsworth, {Stephen Roger} and Kitching, {Arthur Richard} and Joshua Ooi",
year = "2013",
doi = "10.1016/j.cellimm.2013.04.007",
language = "English",
volume = "282",
pages = "21 -- 27",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Myeloperoxidase (MPO)-specific CD4+ T cells contribute to MPO-anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis

AU - Gan, Poh Yi

AU - Holdsworth, Stephen Roger

AU - Kitching, Arthur Richard

AU - Ooi, Joshua

PY - 2013

Y1 - 2013

N2 - Autoimmunity to the neutrophil enzyme myeloperoxidase (MPO) is an important cause of rapidly progressive glomerulonephritis, but the relative roles of MPO-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and autoreactive effector MPO-specific CD4+ T cells are unclear. We confirmed that passive transfer of murine MPO-ANCA to agammaglobulinemic muMT mice immunized with OVA induces glomerular injury with capillary wall thickening, fibrinoid necrosis, mesangial cell proliferation, and periglomerular cell infiltration. Preimmunization of muMT mice with MPO induced MPO-specific CD4+ T cells and significantly enhanced renal injury after MPO-ANCA transfer. CD4+ T cell depletion prevented this augmentation of injury, confirming the importance of effector T cells in the development of MPO-ANCA associated glomerulonephritis. Therefore, MPO-ANCA can induce glomerulonephritis through both direct humoral mechanisms (recruitment of neutrophils and deposition of MPO) and indirectly by initiating MPO deposition in glomeruli, thereby directing effector CD4+ T cell mediated injury. To confirm and support this data, we transferred T cells from MPO-immunized Mpo-/-muMT mice into Rag1-/- mice (control mice received ovalbumin specific T cells) and triggered injury by passive MPO-ANCA. Renal injury was significantly greater in mice transferred with T cells from MPO-immunized mice. These current studies demonstrate that MPO-ANCA induces injury via both humoral and cell mediated immune mechanisms.

AB - Autoimmunity to the neutrophil enzyme myeloperoxidase (MPO) is an important cause of rapidly progressive glomerulonephritis, but the relative roles of MPO-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and autoreactive effector MPO-specific CD4+ T cells are unclear. We confirmed that passive transfer of murine MPO-ANCA to agammaglobulinemic muMT mice immunized with OVA induces glomerular injury with capillary wall thickening, fibrinoid necrosis, mesangial cell proliferation, and periglomerular cell infiltration. Preimmunization of muMT mice with MPO induced MPO-specific CD4+ T cells and significantly enhanced renal injury after MPO-ANCA transfer. CD4+ T cell depletion prevented this augmentation of injury, confirming the importance of effector T cells in the development of MPO-ANCA associated glomerulonephritis. Therefore, MPO-ANCA can induce glomerulonephritis through both direct humoral mechanisms (recruitment of neutrophils and deposition of MPO) and indirectly by initiating MPO deposition in glomeruli, thereby directing effector CD4+ T cell mediated injury. To confirm and support this data, we transferred T cells from MPO-immunized Mpo-/-muMT mice into Rag1-/- mice (control mice received ovalbumin specific T cells) and triggered injury by passive MPO-ANCA. Renal injury was significantly greater in mice transferred with T cells from MPO-immunized mice. These current studies demonstrate that MPO-ANCA induces injury via both humoral and cell mediated immune mechanisms.

UR - http://www.sciencedirect.com/science/article/pii/S0008874913000580

U2 - 10.1016/j.cellimm.2013.04.007

DO - 10.1016/j.cellimm.2013.04.007

M3 - Article

VL - 282

SP - 21

EP - 27

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 1

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