alexa Anti-Citrullinated Protein Antibodies as Novel Therapeutic Drugs in Rheumatoid Arthritis | OMICS International | Abstract
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Research Article

Anti-Citrullinated Protein Antibodies as Novel Therapeutic Drugs in Rheumatoid Arthritis

Renato G.S. Chirivi, Guido J. Jenniskens, and Jos M.H. Raats*
ModiQuest B.V., Oss, The Netherlands
Corresponding Author : Jos M.H. Raats
ModiQuest B.V., Pivot Park-LSC
Molenweg 79, 5349 AC Oss, The Netherlands
Tel: +31-412-846-000
Fax: +31-412-846-009
E-mail: [email protected]
Received November 30, 2012; Accepted January 24, 2013; Published January 30, 2013
Citation: Chirivi RGS, Jenniskens GJ, Raats JMH (2013) Anti-Citrullinated Protein Antibodies as Novel Therapeutic Drugs in Rheumatoid Arthritis. J Clin Cell Immunol S6:006. doi:10.4172/2155-9899.S6-006. doi:10.4172/2155-9899.S6-006
Copyright: © 2013 Chirivi RGS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related article at
DownloadPubmed DownloadScholar Google

Abstract

We have developed a novel antibody-based treatment for rheumatoid arthritis. In a collagen antibody-induced arthritis mouse model, anti-citrullinated protein antibodies (ACPAs) prevent the onset and/or exacerbation of inflammation, and prevent or strongly reduce joint damage. For the development of this novel therapy, we focussed on rheumatoid arthritis-specific citrullinated peptide epitopes. A growing number of studies indicate that modifications of arginines into citrulline residues are responsible for the initial triggering of autoimmunity and the breaking of tolerance. We identified a subset of human recombinant ACPAs that prevent the onset of inflammation in both collagen-induced arthritis and collagen antibody-induced arthritis mouse models for rheumatoid arthritis. Therapeutic administration of these antibodies resulted in the arrest of the inflammation and prevented a further increase of the inflammatory response. Prophylactic administration significantly prevented the onset of inflammation. Histological analysis of inflamed joints from ACPA treated mice revealed a significant decrease in joint damage, as compared to control animals. To identify the differentiating therapeutic epitope recognized by the therapeutic ACPA (tACPA), we performed comparative immunoprecipitations with therapeutic and non-therapeutic ACPAs using human PAD4- deiminated HEK-293 cell lysates, followed by mass spectrometry analysis. The differentiating peptide epitope that is recognized by tACPAs only, is a citrullinated domain of Histone-2A. A second generation of antibodies was selected against this domain by means of phage display and by hybridoma generation. The second generation of tACPAs was comprised of even more potent inhibitors of the inflammatory response. Here, we describe the identification of a series of antibodies directed against a citrullinated epitope present in murine and human histone-2A. In mouse models for rheumatoid arthritis we demonstrate that these tACPAs exhibit a strong anti-inflammatory activity and prevent the occurrence of swelling and joint damage. We propose anti-histone-2A tACPA as a novel therapeutic treatment for rheumatoid arthritis patients.

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version