Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene

Alexander J. Szalai, Casey T. Weaver, Mark A. McCrory, Frederik W. Van Ginkel, Rachael M. Reiman, John F. Kearney, Tony Marion, John E. Volanakis

Research output: Contribution to journalArticle

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Abstract

Objective. Human C-reactive protein (CRP) binds apoptotic cells and alters blood clearance of injected chromatin in mice. To test whether CRP participates in the pathogenesis of systemic lupus erythematosus (SLE), we examined disease development in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice expressing a human CRP transgene (hCRPtg/BW). Methods. Mortality was monitored, proteinuria was determined by dipstick, and serum levels of human CRP and anti-double-stranded DNA (anti-dsDNA) were determined by enzyme-linked immunosorbent assay in NZB/NZW and hCRPtg/BW mice. Thin sections of kidneys were analyzed by immunofluorescence microscopy to compare deposition of IgG, IgM, C3, and human CRP, and electron microscopy was used to reveal differences in ultrastructure. In situ hybridization was performed to detect human CRP messenger RNA expression. Results. The hCRPtg/BW mice had less proteinuria and longer survival than NZB/NZW mice. They also had lower IgM and higher IgG anti-dsDNA titers than NZB/NZW mice, although the differences were transient and small. In hCRPtg/BW mice, accumulation of IgM and IgG in the renal glomeruli was delayed, reduced, and more mesangial than in NZB/NZW mice, while end-stage accumulation of IgG, IgM, and C3 in the renal cortex was prevented. There was less glomerular podocyte fusion, basement membrane thickening, mesangial cell proliferation, and occlusion of capillary lumens in hCRPtg/BW mice, but dense deposits in the mesangium were increased. With disease progression in hCRPtg/BW mice, there was little rise in the plasma CRP level, but CRP in the kidneys became increasingly apparent due to local, disease-independent, age-related expression of the transgene. Conclusion. In hCRPtg/BW mice, CRP protects against SLE by increasing blood and mesangial clearance of immune complexes and by preventing their accumulation in the renal cortex.

Original languageEnglish (US)
Pages (from-to)1602-1611
Number of pages10
JournalArthritis and rheumatism
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2003

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Transgenes
C-Reactive Protein
Immunoglobulin M
Kidney
Immunoglobulin G
Proteinuria
Systemic Lupus Erythematosus
Podocytes
Mesangial Cells
Protein C
Antigen-Antibody Complex
Fluorescence Microscopy
Basement Membrane
Chromatin
In Situ Hybridization
Disease Progression
Blood Proteins
Blood Cells
Electron Microscopy
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Szalai, A. J., Weaver, C. T., McCrory, M. A., Van Ginkel, F. W., Reiman, R. M., Kearney, J. F., ... Volanakis, J. E. (2003). Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene. Arthritis and rheumatism, 48(6), 1602-1611. https://doi.org/10.1002/art.11026

Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene. / Szalai, Alexander J.; Weaver, Casey T.; McCrory, Mark A.; Van Ginkel, Frederik W.; Reiman, Rachael M.; Kearney, John F.; Marion, Tony; Volanakis, John E.

In: Arthritis and rheumatism, Vol. 48, No. 6, 01.06.2003, p. 1602-1611.

Research output: Contribution to journalArticle

Szalai, AJ, Weaver, CT, McCrory, MA, Van Ginkel, FW, Reiman, RM, Kearney, JF, Marion, T & Volanakis, JE 2003, 'Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene', Arthritis and rheumatism, vol. 48, no. 6, pp. 1602-1611. https://doi.org/10.1002/art.11026
Szalai AJ, Weaver CT, McCrory MA, Van Ginkel FW, Reiman RM, Kearney JF et al. Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene. Arthritis and rheumatism. 2003 Jun 1;48(6):1602-1611. https://doi.org/10.1002/art.11026
Szalai, Alexander J. ; Weaver, Casey T. ; McCrory, Mark A. ; Van Ginkel, Frederik W. ; Reiman, Rachael M. ; Kearney, John F. ; Marion, Tony ; Volanakis, John E. / Delayed lupus onset in (NZB × NZW)F1 mice expressing a human C-reactive protein transgene. In: Arthritis and rheumatism. 2003 ; Vol. 48, No. 6. pp. 1602-1611.
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AU - Szalai, Alexander J.

AU - Weaver, Casey T.

AU - McCrory, Mark A.

AU - Van Ginkel, Frederik W.

AU - Reiman, Rachael M.

AU - Kearney, John F.

AU - Marion, Tony

AU - Volanakis, John E.

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