In vitro eradication of citrullinated protein specific B-lymphocytes of rheumatoid arthritis patients by targeted bifunctional nanoparticles

Arthritis Research & Therapy
Judit PozsgayGabriella Sarmay

Abstract

Autoreactive B cells are crucial players in the pathogenesis of rheumatoid arthritis (RA). Autoantibodies specific for citrullinated proteins (ACPA), present in the serum of approximately 60-70 % of patients, have a pathogenic role in the disease. B cell depleting therapies may result in a transient immunosuppression, increasing the risk of infections. Our aim was to develop a new therapeutic approach to selectively deplete the ACPA producing autoreactive B cells. To target B cells synthetic citrullinated peptide derived from the β chain of fibrin, β60-74Cit 60,72,74 (β60-74Cit), the predominant epitope recognized by ACPA was used. Complement dependent cytotoxicity (CDC) was induced by a modified peptide derived from gp120 of HIV-1. To trigger CDC both the targeting peptide and the complement activating peptide were covalently coupled in multiple copies to the surface of poly (DL-lactic-co-glycolic acid) nanoparticles (NPs). Ex vivo antibody synthesis was examined by ELISA and ELISpot. CDC was tested after dead cell staining by flow cytometry. The β60-74Cit peptide was selectively recognized by a small subset of B cells from RA patients having high level of peptide specific serum antibody, suggesting that the peptide can target...Continue Reading

References

Feb 24, 2001·Arthritis and Rheumatism·C C Reparon-SchuijtC L Verweij
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Masson-BessièreG Serre
Jun 9, 2001·Rheumatic Diseases Clinics of North America·S E Gabriel
Nov 8, 2003·Trends in Molecular Medicine·Ryo YamadaKazuhiko Yamamoto
Apr 16, 2005·European Journal of Immunology·Harald BurkhardtRikard Holmdahl
Jun 14, 2005·Biochemical and Biophysical Research Communications·Akari SuzukiKazuhiko Yamamoto
Nov 10, 2005·Arthritis Research & Therapy·Andrew KinlochPatrick J Venables
Aug 22, 2006·Autoimmunity Reviews·Lorena Martinez-GamboaThomas Dörner
Sep 30, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jennifer H AnolikIñaki Sanz
Jun 26, 2007·Journal of Medicinal Chemistry·María L PérezIsabel Haro
Aug 1, 2007·Arthritis and Rheumatism·Holger BangGerd-R Burmester
Jan 5, 2008·Annual Review of Immunology·Lars KlareskogLars Alfredsson
Jun 24, 2008·Joint, Bone, Spine : Revue Du Rhumatisme·Jean SibiliaXavier Mariette
Mar 2, 2010·Current Opinion in Pharmacology·Annett M Jacobi, Thomas Dörner
May 28, 2010·Arthritis and Rheumatism·J-E GottenbergUNKNOWN AutoImmunity and Rituximab registry and French Society of Rheumatology
Feb 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Luca BolognaJosée Golay
Jun 8, 2011·Nature Reviews. Rheumatology·Walther J van VenrooijGer J M Pruijn
Oct 15, 2011·Annals of the Rheumatic Diseases·Annemiek WillemzeLeendert A Trouw
Feb 22, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria F BellatinPeter Stastny
Apr 17, 2012·The Journal of Clinical Investigation·Ulrike HarreGeorg Schett
Mar 5, 2013·Journal of Immunological Methods·Maja JahnmatzNiklas Ahlborg
Feb 24, 2015·Molecular Immunology·Joost P M MelisPaul W H I Parren
Mar 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florence AnquetilMireille Sebbag

❮ Previous
Next ❯

Citations

Jul 14, 2017·Nature Reviews. Rheumatology·Judit PozsgayGabriella Sármay
Jan 25, 2018·International Journal of Molecular Sciences·Eszter SzarkaGabriella Sármay
Aug 12, 2016·Physiological Reviews·Michael J Berridge
Mar 15, 2018·Current Opinion in Rheumatology·Lazaros I Sakkas, Dimitrios P Bogdanos
Jun 29, 2017·Clinical Rheumatology·Talita Siara Almeida BaptistaMoisés Evandro Bauer
Feb 23, 2021·Joint, Bone, Spine : Revue Du Rhumatisme·Audrey PageFrançois-Loïc Cosset
Aug 21, 2021·Drug Delivery and Translational Research·Allen B Tu, Jamal S Lewis
Mar 6, 2019·ACS Chemical Biology·Kyle J BednarMatthew S Macauley
Sep 17, 2019·Bioconjugate Chemistry·Sangita KhatriKira Astakhova

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
dynamic light scattering
flow cytometry

Software Mentioned

GRAPHPAD PRISM
GraphPad
FlowJo

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.