National Alopecia Areata Registry

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National Alopecia Areata Registry

• Madeleine Duvic, MD
• Professor of Medicine Dermatology
• MD Anderson Cancer Center
• Houston, Texas

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Investigators

• Angela Christiano Columbia, NYC
• Maria Hordinsky Univ of Minnesota
• David Norris Univ of Colorado
• Vera Price Univ of California, SF
• Madeleine Duvic Univ Texas
• Chris Amos - Bioinformatics

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Purpose of the AA Registry

• 1. To find and collect samples from multiplex
  families, siblings, and individuals with alopecia
  areata of all severities.
• 2. To encourage research using the data and
  samples from the registry.
• 3. Information used to understand disease, find
  effective treatment, and cure.

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HYPOTHESIS Alopecia Areata is

• Genetic - Host determined, HLA restricted
• Organ specific T-cell mediated directed to the
  hair follicle
• AND Environmental - Triggered by an external
  event, a viral infection or vaccine or stress??
• Mediated by cytokines neuropeptides locally.

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Class II HLA Genes in AA

• CLASS II MHC (DR,DQ,DP) ASSOCIATIONS
• HLA-DR4, DR5 (Italian, Danish, English)
  HLA-DR7 (Russians)
• The HLA-DR5 allele 1104-patchy early onset
• 80 of AA have HLA-DQB103 alleles associated
  with HLA- DR5
• MICA alleles assoc with AA NK receptor
• Welsh/Duvic JID 103 758,1994
• Colombe/Price JAAD 33757, 1995

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AA in Identical Twins

• 55 concordancy in monozygotic twins.
• More severe in first affected, MgtgtF.
• All had HLA-DQ 0302
• Stress was precipitating factor
• No association with CMV

• Jackow Duvic, JAAD 1998.

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Alopecia Areata Registry

• Funded by NIAMS, September 23, 2000
• Self registration for Alopecia Areata via web or
  paper-based questionnaire/database
• and
• Blood samples (DNA, serum, LB lines) from
  examined confirmed AA patients and multiplex
  families.

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Structure of AA Registry
REFER By local Dermatologist
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Registration is Two Steps

• Step One US AA patients confirmed by
  dermatologist asked to fill out short form.
• (Web, Doctor or patient initiated)
• Step Two patient invited to visit one of 5
  sites (or outside derm) to do questionnaire, exam
  and sample collection
• DNA, LB, sera
• Optional photos, quality of life

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AlopeciaAreataRegistry.org REGISTRATION on WEB
or Print-out, Fill-out, Mail or Fax
in.Brochures available
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(No Transcript)
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Informed consent confidentiality

• Patients sign 3 written consents to participate
  in step 2 of the registry.
• Description, pros and cons.
• Children can give assent
• Info is confidential deidentified personnal code
  a family code are given
• Relational databases Microsoft sequel server
  Short, long, laboratory, QOL

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Selection for the Second Step

• Single patients examined at site.
• AT/AU for gt 1 year
• Patchy persistent AA for gt 1 year
• Transient AA for lt 6 or lt 12 mos. with complete
  regrowth
• Unrelated Normal controls are just as important
  as AA subjects.

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Real time report First Tier Registration
10-14-08

• Total individuals registered - 6,469
• Females 4,399 vs Males 2,070
• Racial Breakdown
• - White 4978 AA 283 hispanic 365, asian 233
• Am Indian/Alaska 25 pacific 16
• mixed 293, unknown 192 other 120

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Second Tier Report 10-14-08

• Total Registrants - 2397 (37 of 1st tier)
• Females 1642 (37)
• Males - 750 (36)
• White - 1791 (36)
• Afr Am - 88 (31)
• Hispanic - 159 (43)
• Asian - 125 (54)

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Second Tier Registrantsby Phenotype Severity

• Phenotype
• Transient AA (AAT) 306
• Persistent Patchy AA (AAP) 485
• Alopecia Totalis (AT) 183
• Alopecia Universalis (AU) 676
• Controls related 386
• Controls - unrelated 348
• Total 2,383

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AA Registry Goals

• 1000 AU and AT (859)
• 500 AAP (persistent) (485)
• 250 AAT (transient) (183)
• ANOVA, Generalized Linear models GLM used to
  look at age of onset, gender and severity

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AGE OF ONSET vs AA INDIVIDUALS AFFECTED
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Age of Onset AA Registry

• There are two peaks between 1-12 yrs
• and 25-35yrs
• Speculation
• First peak genetically influenced
• Second peak environmentally induced

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• 57 acquire AA before age 20
• Males develop AA 2.5 yrs earlier than Females
• AU and AT age of onset earlier compared to AAP
  and AAT groups (plt0.0001)
• AT develops 5 years earlier than AU
• Possibly because AT can progress to AU
• AU patients develop disease 4 years earlier than
  those with AAT assuming other factors are held
  constant

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AA Research Progress

• Confirmed the HLA associations
• Studies of cytokine profiles in AA with or
  without atopy.
• Case Control Study - Incidence of autoimmunity in
  AA patients
• EBV trigger for AA in adolescents
• Treatment Practices in AA
• Quality of life in adolescents with AA
• Linkage studies

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Multiplex FamilyNo AA 1,2,3,6 and Yes 4, 5
4,5
1,2
3,6
2,4
AU
1,5
5,6
2,3
4,6
3,4
1,4
AA
4,5
4,5
1,3
AA
AU
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Genome - Families

• 20 families -102 affected, 118 unaffected
• US and Israel families
• Susceptibility found on Chromosomes
• 6 ASP LOD gt2.00 several incl MHC
• 16 \ASP/LOD 3.11 Ps locus
• 18 - LOD 3.93 Ps Locus

Am J Hum Genet. 2007 Feb80(2)316-28. Epub 2007
Jan 5.
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Genome Wide Search

• First screen of SNPs associated with other
  autoimmune disease genes.
• Second Assessment of genetic background of AA
  patients to match controls (n 2000).
• Third full genome SNP search 1000 AU/AT severe
  patients, Alumina chip
• Angela Christiano and Peter Griegerson

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Other Planned Studies

• Case Control Study associations with asthma,
  autoimmune disease
• Second study in identical twins
• Validation and study of Quality of Life
  assessments administered to patients.
• Epidemiology evaluation
• Investigator initiated studies

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The registry is one room with five desks and lots
of filing cabinets
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Our laboratory Team is standing by waiting for
your samples!!
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Conclusions

• AAR is a prototype of a web-based, patient
  friendly patient REGISTRY at five cooperating
  institutions (and IRBs).
• Physician exam required to certify AA.
• Epidemiology, autoimmunity, treatment and quality
  of life data.
• Samples collected prospectively DNA, sera and
  LB lines.

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Acknowledgements
AlopeciaAreataRegistry.org

• NIAMS NAAF for support
• Steering committee and sites Drs. Hordinsky,
  Price, Norris, Christiano
• Advisors Alan Moshell, Vickie Kalabokas, Jorge
  Oxenberg, Kurt Stenn, Lowell Goldsmith.
• All of the families, individuals, med students
  who have participated to make this a success.

mduvic_at_mdanderson.org