Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies

Arthritis & Rheumatology
Changrong GeRikard Holmdahl

Abstract

Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recogn...Continue Reading

References

Feb 14, 1998·The Journal of Clinical Investigation·G A SchellekensW J van Venrooij
Jan 22, 2000·Arthritis and Rheumatism·G A SchellekensW J van Venrooij
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deepak T NairDinakar M Salunke
Jul 12, 2002·Arthritis Research·Günter Steiner, Josef Smolen
Apr 3, 2004·Arthritis Research & Therapy·Erik R VossenaarHenri A Ménard
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·E Krissinel, K Henrick
Dec 22, 2005·Acta Crystallographica. Section D, Biological Crystallography·Philip Evans
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Feb 11, 2009·The Journal of Experimental Medicine·Hüseyin UysalRikard Holmdahl
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jun 1, 2004·Journal of Applied Crystallography·Nicholas K SauterPaul D Adams
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 17, 2012·The Journal of Clinical Investigation·Ulrike HarreGeorg Schett
Oct 19, 2012·Protein Science : a Publication of the Protein Society·Nicole Hartwig TrierGunnar Houen
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Graeme WinterStephen M Prince
May 2, 2014·Mediators of Inflammation·Agata N BurskaFrederique Ponchel
Apr 1, 2015·Nature Communications·Ulrike HarreGeorg Schett
Nov 29, 2015·Annals of the Rheumatic Diseases·Gustaf WigerbladCamilla I Svensson
Dec 15, 2015·PloS One·Nicole Hartwig TrierGunnar Houen
Jun 28, 2016·Scandinavian Journal of Clinical and Laboratory Investigation·Catharina E DamNicole H Trier
Dec 6, 2016·Nature Reviews. Immunology·Vivianne MalmströmLars Klareskog

❮ Previous
Next ❯

Citations

Apr 22, 2019·Annals of the Rheumatic Diseases·René Toes, David S Pisetsky
Mar 13, 2019·Arthritis & Rheumatology·Miriam A Shelef
Dec 18, 2019·Immunological Reviews·Mikhail VolkovDiane van der Woude
Jun 4, 2019·Annals of the Rheumatic Diseases·Arieke Suzanna Berendina KampstraRené E M Toes
Jun 23, 2019·Annals of the Rheumatic Diseases·Rikard Holmdahl
Jun 6, 2020·Arthritis & Rheumatology·Peter SahlströmCaroline Grönwall
Jul 31, 2020·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Sep 25, 2020·Zeitschrift für Rheumatologie·H U Scherer
Jan 11, 2019·Nature Reviews. Rheumatology·Lotte A van de Stadt, Theo Rispens
Sep 24, 2019·Antibodies·Nicole H TrierGunnar Houen
Jun 30, 2019·Nature Reviews. Rheumatology·Changrong Ge, Rikard Holmdahl
Aug 21, 2021·Drug Delivery and Translational Research·Allen B Tu, Jamal S Lewis
May 8, 2020·Journal of Chemical Information and Modeling·Samo LešnikJanez Konc
Sep 9, 2021·Clinical Reviews in Allergy & Immunology·Maria V SokolovaUlrike Steffen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.