Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis

Linda Myers, B. Tang, David Brand, E. F. Rosloniec, John Stuart, Andrew Kang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective. Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII 256-276(N263, D266), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. Methods. Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F263 to N and E 266 to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). Results. The mutant rCII(N263, D266) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII256-276(N263, D 266). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N 263, D266). Administration of rCII(N263, D 266) was ineffective in suppressing arthritis in IL4-/- mice, suggesting that the profound suppressive effects of rCII(N263, D266) were mediated through the production of interleukin-4. Conclusion. These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.

Original languageEnglish (US)
Pages (from-to)3004-3011
Number of pages8
JournalArthritis and rheumatism
Volume50
Issue number9
DOIs
StatePublished - Sep 1 2004

Fingerprint

Collagen Type II
Arthritis
T-Lymphocytes
Interleukin-4
Transgenic Mice
Peptide T
Experimental Arthritis
Baculoviridae
Amino Acid Substitution
Autoimmunity
Point Mutation
Immunotherapy
Antibody Formation
Collagen
Cytokines
Technology
Peptides
Incidence

All Science Journal Classification (ASJC) codes

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

Cite this

Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis. / Myers, Linda; Tang, B.; Brand, David; Rosloniec, E. F.; Stuart, John; Kang, Andrew.

In: Arthritis and rheumatism, Vol. 50, No. 9, 01.09.2004, p. 3004-3011.

Research output: Contribution to journalArticle

@article{944bd01731504fb9af09be4ee611f6a4,
title = "Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis",
abstract = "Objective. Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII 256-276(N263, D266), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. Methods. Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F263 to N and E 266 to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). Results. The mutant rCII(N263, D266) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII256-276(N263, D 266). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N 263, D266). Administration of rCII(N263, D 266) was ineffective in suppressing arthritis in IL4-/- mice, suggesting that the profound suppressive effects of rCII(N263, D266) were mediated through the production of interleukin-4. Conclusion. These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.",
author = "Linda Myers and B. Tang and David Brand and Rosloniec, {E. F.} and John Stuart and Andrew Kang",
year = "2004",
month = "9",
day = "1",
doi = "10.1002/art.20491",
language = "English (US)",
volume = "50",
pages = "3004--3011",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

TY - JOUR

T1 - Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis

AU - Myers, Linda

AU - Tang, B.

AU - Brand, David

AU - Rosloniec, E. F.

AU - Stuart, John

AU - Kang, Andrew

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Objective. Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII 256-276(N263, D266), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. Methods. Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F263 to N and E 266 to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). Results. The mutant rCII(N263, D266) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII256-276(N263, D 266). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N 263, D266). Administration of rCII(N263, D 266) was ineffective in suppressing arthritis in IL4-/- mice, suggesting that the profound suppressive effects of rCII(N263, D266) were mediated through the production of interleukin-4. Conclusion. These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.

AB - Objective. Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII 256-276(N263, D266), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. Methods. Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F263 to N and E 266 to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). Results. The mutant rCII(N263, D266) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII256-276(N263, D 266). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N 263, D266). Administration of rCII(N263, D 266) was ineffective in suppressing arthritis in IL4-/- mice, suggesting that the profound suppressive effects of rCII(N263, D266) were mediated through the production of interleukin-4. Conclusion. These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.

UR - http://www.scopus.com/inward/record.url?scp=4444292398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444292398&partnerID=8YFLogxK

U2 - 10.1002/art.20491

DO - 10.1002/art.20491

M3 - Article

VL - 50

SP - 3004

EP - 3011

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 9

ER -