Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers

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Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies : Evaluation of Dose, Frequency, and Biomarkers. / Boysen, Lykke; Viuff, Birgitte M.; Landsy, Lone H.; Lykkesfeldt, Jens; Raymond, James T.; Price, Shari A.; Pelzer, Hermann; Lauritzen, Brian.

In: Toxicologic Pathology, Vol. 48, No. 4, 2020, p. 570-585.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Boysen, L, Viuff, BM, Landsy, LH, Lykkesfeldt, J, Raymond, JT, Price, SA, Pelzer, H & Lauritzen, B 2020, 'Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers', Toxicologic Pathology, vol. 48, no. 4, pp. 570-585. https://doi.org/10.1177/0192623320919121

APA

Boysen, L., Viuff, B. M., Landsy, L. H., Lykkesfeldt, J., Raymond, J. T., Price, S. A., Pelzer, H., & Lauritzen, B. (2020). Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers. Toxicologic Pathology, 48(4), 570-585. https://doi.org/10.1177/0192623320919121

Vancouver

Boysen L, Viuff BM, Landsy LH, Lykkesfeldt J, Raymond JT, Price SA et al. Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers. Toxicologic Pathology. 2020;48(4):570-585. https://doi.org/10.1177/0192623320919121

Author

Boysen, Lykke ; Viuff, Birgitte M. ; Landsy, Lone H. ; Lykkesfeldt, Jens ; Raymond, James T. ; Price, Shari A. ; Pelzer, Hermann ; Lauritzen, Brian. / Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies : Evaluation of Dose, Frequency, and Biomarkers. In: Toxicologic Pathology. 2020 ; Vol. 48, No. 4. pp. 570-585.

Bibtex

@article{4ee4d5257fc94d05b01f3f2adc714564,
title = "Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers",
abstract = "Administration of human protein–based drugs to animals often leads to formation of antidrug antibodies (ADAs) that may form circulating immune complexes (CICs) with the dosed protein. Circulating immune complexes can activate and bind complement (cCICs), and if large amount of CICs or cCICs is formed, the clearance mechanism potentially becomes saturated, which can lead to immune complex (IC) deposition and inflammation. To obtain a better understanding of the underlying factors, including the relationship between different dose regimes on IC formation and deposition and identification of possible biomarkers of IC deposition and IC-related pathological changes in kidneys, BALB/c and C57BL/6J mice were administered with human anti-tumor necrosis factor α (aTNFα, adalimumab) or a humanized anti-TNP (aTNP) antibody for 13 weeks. Particularly, ADA, CIC, cCIC formation, IC deposition, and glomerulonephritis were observed in C57BL/6J administered with aTNFα, whereas the immunologic response was minor in BALB/c mice administered with aTNFα and in BALB/c and C57BL/6J mice administered aTNP. Changing dose levels or increasing dosing frequency of aTNFα on top of an already-established CIC and cCIC response did not lead to substantial changes in CIC, cCIC formation, or IC deposition. Finally, no association between the presence of CICs or cCIC in plasma and glomerular IC deposition and/or glomerulonephritis was observed.",
keywords = "complement, glomerulonephritis, immune complex, immunogenicity, monoclonal antibodies, mouse",
author = "Lykke Boysen and Viuff, {Birgitte M.} and Landsy, {Lone H.} and Jens Lykkesfeldt and Raymond, {James T.} and Price, {Shari A.} and Hermann Pelzer and Brian Lauritzen",
year = "2020",
doi = "10.1177/0192623320919121",
language = "English",
volume = "48",
pages = "570--585",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications",
number = "4",

}

RIS

TY - JOUR

T1 - Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies

T2 - Evaluation of Dose, Frequency, and Biomarkers

AU - Boysen, Lykke

AU - Viuff, Birgitte M.

AU - Landsy, Lone H.

AU - Lykkesfeldt, Jens

AU - Raymond, James T.

AU - Price, Shari A.

AU - Pelzer, Hermann

AU - Lauritzen, Brian

PY - 2020

Y1 - 2020

N2 - Administration of human protein–based drugs to animals often leads to formation of antidrug antibodies (ADAs) that may form circulating immune complexes (CICs) with the dosed protein. Circulating immune complexes can activate and bind complement (cCICs), and if large amount of CICs or cCICs is formed, the clearance mechanism potentially becomes saturated, which can lead to immune complex (IC) deposition and inflammation. To obtain a better understanding of the underlying factors, including the relationship between different dose regimes on IC formation and deposition and identification of possible biomarkers of IC deposition and IC-related pathological changes in kidneys, BALB/c and C57BL/6J mice were administered with human anti-tumor necrosis factor α (aTNFα, adalimumab) or a humanized anti-TNP (aTNP) antibody for 13 weeks. Particularly, ADA, CIC, cCIC formation, IC deposition, and glomerulonephritis were observed in C57BL/6J administered with aTNFα, whereas the immunologic response was minor in BALB/c mice administered with aTNFα and in BALB/c and C57BL/6J mice administered aTNP. Changing dose levels or increasing dosing frequency of aTNFα on top of an already-established CIC and cCIC response did not lead to substantial changes in CIC, cCIC formation, or IC deposition. Finally, no association between the presence of CICs or cCIC in plasma and glomerular IC deposition and/or glomerulonephritis was observed.

AB - Administration of human protein–based drugs to animals often leads to formation of antidrug antibodies (ADAs) that may form circulating immune complexes (CICs) with the dosed protein. Circulating immune complexes can activate and bind complement (cCICs), and if large amount of CICs or cCICs is formed, the clearance mechanism potentially becomes saturated, which can lead to immune complex (IC) deposition and inflammation. To obtain a better understanding of the underlying factors, including the relationship between different dose regimes on IC formation and deposition and identification of possible biomarkers of IC deposition and IC-related pathological changes in kidneys, BALB/c and C57BL/6J mice were administered with human anti-tumor necrosis factor α (aTNFα, adalimumab) or a humanized anti-TNP (aTNP) antibody for 13 weeks. Particularly, ADA, CIC, cCIC formation, IC deposition, and glomerulonephritis were observed in C57BL/6J administered with aTNFα, whereas the immunologic response was minor in BALB/c mice administered with aTNFα and in BALB/c and C57BL/6J mice administered aTNP. Changing dose levels or increasing dosing frequency of aTNFα on top of an already-established CIC and cCIC response did not lead to substantial changes in CIC, cCIC formation, or IC deposition. Finally, no association between the presence of CICs or cCIC in plasma and glomerular IC deposition and/or glomerulonephritis was observed.

KW - complement

KW - glomerulonephritis

KW - immune complex

KW - immunogenicity

KW - monoclonal antibodies

KW - mouse

U2 - 10.1177/0192623320919121

DO - 10.1177/0192623320919121

M3 - Journal article

C2 - 32319353

AN - SCOPUS:85083783937

VL - 48

SP - 570

EP - 585

JO - Toxicologic Pathology

JF - Toxicologic Pathology

SN - 0192-6233

IS - 4

ER -

ID: 248556117