• My Dashboard My Education Find an Ophthalmologist
  • Home
  • Coronavirus
  • For Ophthalmologists
    • Meetings
      • AAO 2022
        • Meeting Information
          • Past and Future Meetings
          • Mobile Meeting Guide
          • Contact Information
          • Annual Meeting News
          • Health and Safety
          • Policies and Disclaimers
        • Program
          • Program Highlights
          • Subspecialty Day
          • Virtual Meeting
          • Program Committees
          • CME
          • Meeting Archives
        • Expo
        • Registration
        • Hotels & Travel
          • Hotel Reservation Information
          • Chicago
          • International Attendees
          • Hotel Meeting Space
        • Presenter Central
          • Presenter Central
          • Abstract Selection Process
          • Submission Policies
          • Subject Classification/Topics
          • Instruction Courses and Skills Transfer Labs
          • Papers and Posters
          • Videos
          • Grand Rounds Symposium
          • Program Participant and Faculty Guidelines
          • Faculty Development Program
        • Exhibitors
          • Exhibitor Central
          • Exhibitor Portal Information
          • Exhibitor Prospectus
          • New Exhibiting Companies
          • Exhibitor Resources
          • International Exhibitors
          • Promotional Opportunities
          • Exhibitor Hotel Reservations
      • Mid-Year Forum
        • Registration and Travel
        • Congressional Advocacy Day
        • Advocacy Ambassador Program
        • Program
        • Schedule
        • Sponsored Attendees
        • News
      • Codequest
        • Codequest Instructors
        • Claim Codequest CME or CEU Credit
      • Eyecelerator
    • Clinical Education
      • COVID-19
      • Education
        • Browse All Education
        • Courses
        • Cases
        • Learning Plans
        • Interactive
        • Focal Points
        • Wills Eye Manual
        • Disease Reviews
        • Clinical Webinars
        • Diagnose This
        • Self-Assessments
        • Educational Centers
          • Glaucoma Education Center
          • Pediatric Ophthalmology Education Center
          • Laser Surgery Education Center
          • Myopia Resources
          • Oculofacial Plastic Surgery Center
          • Redmond Ethics Center
      • Journals
      • Guidelines
        • Browse All Practice Guidelines
        • Preferred Practice Patterns
        • Clinical Statements
        • Compendium Guidelines
        • Complementary Therapy Assessments
        • Medical Information Technology
        • Ophthalmic Technology Assessments
        • Patient Safety Statements
        • Choosing Wisely
        • Low Vision
        • Eye Care for Older Adults
        • Eye Disease Statistics
        • About the Hoskins Center
      • Video and Image Library
        • Browse All Videos
        • Clinical and Surgical Videos
        • Presentations and Lectures
        • 1-Minute Videos
        • Master Class Videos
        • Basic Skills Videos
        • Interviews
        • Images
        • Submit an Image
        • Submit a Video
      • Podcasts
        • Browse All Audio and Podcasts
        • Experts InSight
        • Ophthalmology Journal
      • News
        • Browse All Clinical News
        • Editors' Choice
        • Headlines
        • Current Insight
      • CME Central
        • Browse All CME Activities
        • Claim CME Credit and View Transcript
        • CME Planning Resources
        • Complete Your Financial Disclosure
        • Joint Sponsorship Portal
        • LEO Continuing Education Recognition Award
        • Safe ER/LA Opioid Prescribing
        • Check Your Industry Payment Records
      • MOC
      • Resident Education
        • Resident Education Home
        • Browse All Resident Content
          • Courses
          • Flashcards
          • Interactive Cases and Simulations
          • Videos
          • Webinars
        • OKAP and Board Exam Resources
          • OKAP Exam
          • Board Prep Resources
          • OKAP and Board Review Presentations
          • Study Flashcards
        • Cataract Master
        • Diversity and Inclusion Education
        • News and Advice from YO Info
        • Pediatric Ophthalmology Education Center
        • PGY-1 and PGY-2 Resources
        • Simulation in Resident Education
    • Membership
      • Join
      • Renew
      • Current Member
      • Volunteer
      • Physician Wellness
      • Member Directory
      • Member Obituaries
      • AAOE Membership
    • Advocacy
      • Advocacy News
      • Get Involved
        • Ways to Give
        • How to Get Involved
        • Congressional Advocacy
        • Support the Academy's Agenda
        • Research Legislation
        • Find Your Legislators
        • I Am an Advocate
        • Advocacy at Home
        • Advocate Tools
        • Best Practices for Advocating at Home
        • Social Media Toolkit
        • Letter to Editor
        • Town Hall Guide
        • Guide to Engaging With New Lawmakers
        • Resources
        • Attending a Political Fundraiser
      • OPHTHPAC
        • About Us
        • Join OPHTHPAC
        • OPHTHPAC Blog
      • Surgical Scope Fund
        • Support Surgery By Surgeons
        • Surgery By Surgeons Blog
    • Publications
      • EyeNet Magazine
        • Latest Issue
        • Archive
        • Subscribe
        • Advertise
        • Write For Us
        • Corporate Lunches
        • Contact
        • MIPS 2022
      • Focal Points
      • Ophthalmology
      • Ophthalmology Glaucoma
      • Ophthalmology Retina
      • YO Info
      • Scope
    • Subspecialties
      • Cataract/Anterior Segment
      • Comprehensive Ophthalmology
      • Cornea/External Disease
      • Glaucoma
      • Neuro-Ophthalmology/Orbit
      • Ocular Pathology/Oncology
      • Oculoplastics/Orbit
      • Pediatric Ophthalmology/Strabismus
      • Refractive Management/Intervention
      • Retina/Vitreous
      • Uveitis
    • IRIS Registry
      • About
      • Using the Registry
        • User Guide
        • Medicare Reporting
        • Maintenance of Certification
        • Non-EHR Reporting
      • Sign Up
        • Application Process
        • Why Participate
        • Once You've Applied: Getting Started
        • What Practices Are Saying About the Registry
      • Requirements
        • EHR Systems
        • Data & Technical Needs
      • Research
      • Registry Dashboard
      • News
      • Medicare & MIPS
    • Medicare Information
    • Diversity, Equity, and Inclusion
  • For Practice Management
    • Managing Your Practice
      • Managing Your Practice Topics
      • Coronavirus Resources
      • Reopening & Recovery
      • Practice Forms Library
      • Practice Management News and Advice
      • AAOE-Talk
      • Video Library
      • Ophthalmology Job Center
      • Benchmarking and Salary Tools
      • Academy Consultations
      • Consultant Directory
    • Coding
      • Coding Topics
      • Codequest Events
      • Ask the Coding Experts
      • Coding Updates and Resources
      • Coding for Injectable Drugs
      • EM Documentation
      • ICD-10-CM
      • Ophthalmic Coding Specialist (OCS) Exam
      • Retina
      • Savvy Coder
    • Webinars and Events
      • Annual Meeting
      • Codequest Courses
      • Mid-Year Forum
      • Webinar Recordings
    • IRIS Registry
      • Merit-Based Incentive Payment
    • Medicare and MIPS
      • MIPS
        • Quality
        • Promoting Interoperability
        • Improvement Activities
        • Cost
        • Avoid a Penalty
      • Resources
      • Medicare Participation Options
      • Medicare Advantage Plans
      • New Medicare Card
      • Provider Enrollment, Chain and Ownership System (PECOS)
    • Regulatory Compliance
      • HIPPA Resources
      • Office of Inspector General
      • Audits
      • OSHA
    • AAOE Membership
      • Join AAOE
      • Membership Benefits
      • Renew/Pay Dues
    • About AAOE
      • AAOE Board of Directors
      • AAOE Content Committee
      • Volunteer Opportunities
  • For Public & Patients
    • Eye Health A-Z
    • Symptoms
    • Glasses & Contacts
    • Tips & Prevention
    • News
    • Ask an Ophthalmologist
    • Patient Stories
    • No Cost Eye Exams
    • Español
      • A - Z de Salud Ocular
      • Síntomas
      • Anteojos y Lentes de Contacto
      • Consejos y Prevención
      • Noticias
      • Relatos de Pacientes
      • Exámenes de la vista sin costo
      • English
  • AAO 2022
    • Meeting Information
      • Past and Future Meetings
      • Mobile Meeting Guide
      • Contact Information
      • Annual Meeting News
      • Health and Safety
      • Policies and Disclaimers
    • Program
      • Program Highlights
      • Subspecialty Day
      • Virtual Meeting
      • Program Committees
      • CME
      • Meeting Archives
    • Expo
    • Registration
    • Hotels & Travel
      • Hotel Reservation Information
      • Chicago
      • International Attendees
      • Hotel Meeting Space
    • Presenter Central
      • Presenter Central
      • Abstract Selection Process
      • Submission Policies
      • Subject Classification/Topics
      • Instruction Courses and Skills Transfer Labs
      • Papers and Posters
      • Videos
      • Grand Rounds Symposium
      • Program Participant and Faculty Guidelines
      • Faculty Development Program
    • Exhibitors
      • Exhibitor Central
      • Exhibitor Portal Information
      • Exhibitor Prospectus
      • New Exhibiting Companies
      • Exhibitor Resources
      • International Exhibitors
      • Promotional Opportunities
      • Exhibitor Hotel Reservations
  • About
    • Who We Are
      • What We Do
      • About Ophthalmology
      • The Eye Care Team
      • Ethics and the Academy
      • History
      • Museum of Vision
      • Values
    • Governance
      • Council
      • Board of Trustees
      • Committees
      • Academy Past Presidents
      • Secretariats
      • Elections
      • Academy Blog
      • Academy Staff Leadership
    • Leadership Development
    • Awards
      • Laureate Recognition Award
      • Outstanding Advocate Award
      • Outstanding Humanitarian Service Award
      • International Blindness Prevention Award
      • Distinguished Service Award
      • Guests of Honor
      • Secretariat Award
      • Straatsma Award
      • Achievement Award Program
      • Artemis Award
      • EnergEYES Award
      • International Education Award
      • International Scholar Award
      • Commitment to Advocacy Award
      • Visionary Society Award
    • Financial Relationships
    • Policy Statements
    • Related Organizations
      • Subspecialty/Specialized Interest Society Directory
      • State Society Directory
      • Subspecialty/Specialized Interest Society Meetings
      • State Society Meetings
      • Resources for Societies
    • Year in Review
      • 2020 Year in Review
  • Foundation
    • About
      • 2020-2021 Annual Report
      • Annual Report Archives
      • News From the Chair
      • Foundation Staff
    • Our Impact
      • Partners for Sight
      • Donor Spotlights
      • Global Ophthalmic Community
      • Sponsorships
      • Patients and the Public
    • Giving Options
      • Our Supporters
      • Estate and Planned Giving
      • Ophthalmic Business Council
      • Parke Center Campaign
      • Minority Ophthalmology Mentoring Campaign
      • Museum of the Eye Campaign
    • Orbital Gala
      • Why Attend
      • Photo Recap
      • Corporate Support Opportunities
      • Tribute Gifts
      • Silent Auction
      • Corporate Sponsors
    • Donate
    • Museum of the Eye Campaign
      • Museum Supporters
  • Museum of the Eye
    • Visit
    • What's On
      • Museum Galleries
      • Special Exhibitions
      • Current Events
      • Past Events
    • Explore
      • Research and Resources
      • Collection Search
      • Previous Exhibits
      • Oral Histories
      • Biographies
    • Volunteer
    • Mailing List
    • Donate
    • About the Museum
      • Museum Blog
  • Young Ophthalmologists
    • YO Info
    • Learn to Bill
    • Engage with the Academy
  • Senior Ophthalmologists
    • Scope
    • Practice Transitions
  • International Ophthalmologists
    • Global Programs and Resources for National Societies
    • Awards
    • Global Outreach
  • Residents
  • Medical Students
×
Shop
Log In Create an Account
  • For Ophthalmologists
  • For Practice Management
  • For Public & Patients
  • Coronavirus
  • About
  • Foundation
  • Museum of the Eye
  • COVID-19
  • Journals
  • Education
    • Education
    • Courses
    • Cases
    • Learning Plans
    • Interactive
    • Focal Points
    • Wills Eye Manual
    • Disease Reviews
    • Clinical Webinars
    • Diagnose This
    • Self-Assessments
    • Education Centers
      • Glaucoma Education Center
      • Pediatric Ophthalmology Education Center
      • Laser Surgery Education Center
      • Oculofacial Plastic Surgery Center
      • Redmond Ethics Center
      • Myopia Resources
      • Thyroid Eye Disease Resources
  • Guidelines
    • Practice Guidelines
    • Preferred Practice Patterns
    • Clinical Statements
    • Ophthalmic Technology Assessments
    • Patient Safety Statements
    • Complementary Therapy Assessments
    • Compendium Guidelines
    • Medical Information Technology
    • Low Vision
    • Choosing Wisely
    • Eye Care for Older Adults
    • Eye Disease Statistics
    • About the Hoskins Center
    • Artificial Intelligence
    • Premium IOLs
    • Patient-Reported Outcomes with LASIK Symptoms and Satisfaction
  • Multimedia
    • Multimedia Library
    • Video
      • 1-Minute Videos
      • Presentations and Lectures
      • Master Class Videos
      • Basic Skills Videos
      • Clinical and Surgical Videos
      • Interviews
      • Resident Lectures
      • Submit a Video
      • YO Video Contest
    • Podcasts
      • Browse Podcast Archive
      • Experts InSight Podcast
      • Ophthalmology Journal Podcast
    • Images
      • Submit an Image
  • News
    • Clinical News
    • Editors' Choice
    • Headlines
    • Current Insight
  • CME
    • CME Central
    • Claim CME Credit and View Transcript
    • CME Planning Resources
    • Complete Your Financial Disclosure
    • Joint Sponsorship Portal
    • LEO Continuing Education Recognition Award
    • Safe ER/LA Opioid Prescribing
    • Check Your Industry Payment Records
  • MOC
  • Residents
    • Resident Education Home
    • Browse All Resident Content
      • Courses
      • Flashcards and Study Presentations
      • Interactive Cases and Simulations
      • Videos
      • Webinars
    • Cataract Master
    • Diversity and Inclusion Education
    • News and Advice from YO Info
    • OKAP and Board Exam Resources
      • OKAP Exam
      • Board Prep Resources
      • OKAP and Board Review Presentations
      • Study Flashcards
    • Pediatric Ophthalmology Education Center
    • PGY-1 and PGY-2 Resources
    • Resident Knowledge Exchange
    • Simulation in Resident Education
    • Clinical Education /
    • Book Excerpts /
    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    9 Uveitis and Ocular Inflammation

    Chapter 4: Special Topics in Ocular Immunology

    HLA Associations and Disease

    Disease Associations

    In 1973, the first association between an HLA haplotype and a disease—ankylosing spondylitis—was identified. Since then, more than 100 other disease associations have been established, including several for ocular inflammatory diseases (Table 4-1). An HLA–disease association is established when there is a statistically increased frequency of an HLA haplotype in persons with that disease compared with the frequency in a disease-free population. The ratio of the probability of the disease occurring in individuals with the HLA haplotype to individuals without the haplotype is termed relative risk. A relative risk of 1 denotes no difference in risk, <1 indicates a reduced risk, and >1 an increased risk. Several points are important when considering HLA–disease associations:

    • The HLA association identifies individuals at risk, but it is not a diagnostic marker. The associated haplotype is not necessarily present in all people with the disease, nor does its presence in a person ensure the correct diagnosis.

    • The association depends on the validity of the haplotyping. Older literature often reflects associations based on HLA classifications (some provisional) that might have changed.

    • The association is only as strong as the clinical diagnosis. Diseases that are difficult to diagnose based on clinical features may obscure real associations.

    • The concept of linkage disequilibrium proposes that if 2 genes are physically close together on a chromosome, they are likely to be inherited together rather than undergo genetic randomization in a population. Thus, HLA genes may be coinherited with a separate gene that confers the actual risk. Sometimes 2 HLA haplotypes can occur together more frequently than predicted by their independent frequencies in the population.

    For example, approximately 8% of the Caucasian population in the United States is HLA-A29 positive, but fewer than 1 in 10,000 US residents have birdshot chorioretinopathy (although nearly all patients with birdshot chorioretinopathy are HLA-A29 positive). Thus, most individuals who are HLA-A29 positive will never develop birdshot chorioretinopathy. This reinforces that other genetic and environmental factors are implicated. As an example, genes encoding aminopeptidases involved in processing of MHC class I ligands, namely endoplasmic reticulum aminopeptidase (ERAP), have been identified in genome-wide association studies of patients with birdshot chorioretinopathy.

    Table 4-1 HLA Associations and Ocular Inflammatory Disease

    Several mechanisms have been proposed for HLA-disease associations. The most direct theory postulates that HLA molecules act as peptide-binding molecules for etiologic antigens or infectious agents. Thus, individuals bearing a specific HLA molecule might be predisposed to processing certain antigens, such as an infectious agent that cross-reacts with a self-antigen, and other individuals, lacking that haplotype, would not be so predisposed. Specific variations or mutations in the peptide-binding region would greatly influence this mechanism; only molecular typing can detect these variations. Preliminary data in support of this theory is available for patients with type 1 diabetes mellitus.

    A second theory proposes molecular mimicry between bacterial antigens and an epitope on the HLA molecule (ie, an antigenic site on the molecule itself). An appropriate antibacterial effector response might inappropriately initiate a cross-reactive effector response with an epitope of the HLA molecule.

    A third theory suggests that the T-lymphocyte antigen receptor (gene) might be the true susceptibility factor. Because a specific T-lymphocyte receptor uses a specific HLA haplotype, a strong correlation would exist between an HLA and the T-lymphocyte antigen receptor repertoire.

    • Kuiper J, Rothova A, de Boer J, Radstake T. The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers. Prog Retin Eye Res. 2015;44:99–110.

    • Levinson RD. Immunogenetics of ocular inflammatory disease. Tissue Antigens. 2007;69(2):105–112.

    Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

  • Most Commented
    Loading, please wait...
    There are no comments available.
    Most Viewed
    Loading, please wait...
    Most Viewed content is not available.
  • The Academy Store
    2022-2023 Basic and Clinical Science Course, Complete Print Set
    2022-2023 Basic and Clinical Science Course, Complete eBook Set
    2022-2023 Basic and Clinical Science Course, Complete Print and eBook Set
    2022-2023 Basic and Clinical Science Course, Residency Print Set
    2022-2023 Basic and Clinical Science Course, Residency eBook Set
    2022-2023 Basic and Clinical Science Course Complete Set
    2022-2023 Basic and Clinical Science Course Residency Set
    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
    2022-2023 Basic and Clinical Science Course, Section 12: Retina and Vitreous
    2022-2023 Basic and Clinical Science Course, Section 13: Refractive Surgery
    The Technician Point System: How to Improve Practice Accountability and Bottom Line (Free Member Webinar)
    Transitioning Your Practice: Retiring, Selling or Buying a Practice (Free Member Webinar)
    How to Build a Patient-First Culture (Free Member Webinar)
    2022 IRIS Registry (Intelligent Research in Sight) Preparation Kit
    Advances in Medical and Surgical Management: The 2022 Update on Glaucoma
    Presbyopia-Correcting IOLs
    2022 Codequest - Multistate (Recorded March 29)
    2022 Codequest Virtual (Multistate)
    Retina Patient Education Video Collection
    Cataract and Refractive Surgery Patient Education Video Collection
 
  • Contact Us
  • About the Academy
  • Jobs at the Academy
  • Financial Relationships with Industry
  • Medical Disclaimer
  • Privacy Policy
  • Terms of Service
  • Help
  • For Advertisers
  • For Media
  • Ophthalmology Job Center

OUR SITES

  • EyeWiki
  • International Society of Refractive Surgery

FOLLOW THE ACADEMY

Medical Professionals

  • Facebook
  • Twitter
  • LinkedIn
  • YouTube

Public & Patients

  • Facebook
  • Twitter
  • Instagram
  • YouTube

Museum of the Eye

  • Facebook
  • Twitter
  • Instagram
  • YouTube
  • Trip Advisor
  • Yelp
© American Academy of Ophthalmology 2022