The Rheumatologist
COVID-19 News
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Ankylosing Spondylitis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Workforce
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Systemic Lupus Erythematosus Resource Center
      • Rheumatoid Arthritis Resource Center
      • Gout Resource Center
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / 2013 ACR/ARHP Annual Meeting: Genetic Research Yields Clues to Pathogenesis of Rheumatoid Arthritis, Psoriatic Arthritis

2013 ACR/ARHP Annual Meeting: Genetic Research Yields Clues to Pathogenesis of Rheumatoid Arthritis, Psoriatic Arthritis

January 1, 2014 • By Mary Beth Nierengarten

  • Tweet
  • Email
Print-Friendly Version / Save PDF

You Might Also Like
  • 2013 ACR/ARHP Annual Meeting: Researchers Explore Role of Pathogens, Quality of Care in Rheumatoid Arthritis
  • 2013 ACR/ARHP Annual Meeting: Clues to Predictors of Autoimmune Disease Revealed
  • ACR/ARHP Annual Meeting 2012: Genes Not the Only Factor in Susceptibility to Rheumatoid Arthritis
Explore This Issue
January 2014
Also By This Author
  • Resetting Immune Tolerance for the Prevention of RA
Which Arthritis Is It?

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

SAN DIEGO—During the past several decades, an understanding of the pathogenesis of many rheumatic diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), has been illuminated by the discovery of the key role played by certain human leukocyte antigen (HLA) alleles. What is now known, according to Robert Winchester, MD, professor of pediatrics, medicine, and pathology in the department of pathology and cell biology, division of rheumatology, at the College of Physicians and Surgeons of Columbia University in New York, is that both RA and PsA are autoimmune in pathogenesis, and that the most important determinants of disease susceptibility are certain alleles encoding the particular major histocompatibility complex, HLA. “While the roles and significance of the HLA genes differ in these two diseases, the HLA molecules encoded by these genes likely contribute importantly to specifying the type of adaptive immune response that underlies each disease,” he said.

What are the implications of this knowledge on understanding the pathogenesis of RA and PsA? Dr. Winchester walked participants through an answer to this question via an elegant lecture on the meaning and significance of HLA associations in rheumatologic diseases during the 2013 Paul Klemperer, MD, Memorial Lecture, “Rheumatoid Arthritis, Psoriatic Arthritis and Autoimmunity: Good Genes, Elegant Mechanisms, Bad Results,” here at the 2013 ACR/ARHP Annual Meeting, held October 26–30. [Editor’s Note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org/sessionselect.]

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

Adaptive Immune Response

The heart of the adaptive immune response is the T-cell receptor–peptide–HLA molecule interaction, he said, which is also the cornerstone on which the development of autoimmunity rests. Autoimmunity develops through two major consequences that occur when the T cells of the adaptive immune system are challenged to recognize many different pathogen peptides. The first consequence, he said, is somatic generation and thymic selection of T-cell repertoire on self-peptides bound to self-HLA. “Because the entire T-cell portion of the adaptive immune system is built on physiologic self-recognition, this leads to the risk that certain individuals will develop autoimmunity,” he said.

The second consequence is diversification of the HLA system to develop new alleles that better bind these various peptides because of the need of HLA molecules to bind and anchor each of the different pathogen peptides with high affinity, he said. “Since certain HLA molecules bind particular self-peptides that are expressed on cells and tissues comprising the joint, these self-peptides become targets of the autoimmune adaptive immune response,” he said, adding that, “these, in turn, drive the inflammatory response once they are triggered by still-unknown processes.”

Disease Susceptibility: Rheumatoid Arthritis

Citing work done in concert with Peter Gregersen, MD, a geneticist who heads the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute for Medical Research in Manhasset, N.Y., he described what is known about disease susceptibility in RA. Their research shows that RA disease susceptibility is associated with at least eight different alleles of HLA-DR locus, and that each allele encodes a similar sequence (i.e., shared epitope). According to Dr. Winchester, the alleles in patients with RA that are responsible for RA susceptibility are identical in sequence to the alleles in healthy persons (i.e., people with good genes) and are not rare abnormal genes. He said that studies show that at the genotypic level, the risk of RA is additive. For example, the risk conferred by two shared epitope alleles is greater than that conferred by one shared epitope allele. Similarly, the risk conferred by one shared epitope allele is greater than that conferred by alleles lacking the shared epitope structure, although dominant protection is not conferred by any shared epitope negative alleles. “Importantly,” he said, “the clinical phenotype of rheumatoid arthritis is essentially the same regardless of which among the eight alleles a person inherits.”

ad goes here:advert-3
ADVERTISEMENT
SCROLL TO CONTINUE

Pages: 1 2 3 | Single Page

Filed Under: Conditions, Meeting Reports, Rheumatoid Arthritis Tagged With: AC&R, ACR/ARHP Annual Meeting, American College of Rheumatology, Pathogenesis, Psoriatic Arthritis, Research, Rheumatoid arthritisIssue: January 2014

You Might Also Like:
  • 2013 ACR/ARHP Annual Meeting: Researchers Explore Role of Pathogens, Quality of Care in Rheumatoid Arthritis
  • 2013 ACR/ARHP Annual Meeting: Clues to Predictors of Autoimmune Disease Revealed
  • ACR/ARHP Annual Meeting 2012: Genes Not the Only Factor in Susceptibility to Rheumatoid Arthritis
  • Research Reveals Clues Into Inflammatory Process of Crystal Arthropathies Note Experts at the 2013 ACR/ARHP Annual Meeting

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

ACR Convergence

Don’t miss rheumatology’s premier scientific meeting for anyone involved in research or the delivery of rheumatologic care or services.

Visit the ACR Convergence site »

Meeting Abstracts

Browse and search abstracts from the ACR Convergence and ACR/ARP Annual Meetings going back to 2012.

Visit the Abstracts site »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2021 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.