National Alopecia Areata
• Madeleine Duvic, MD
• Professor of Medicine & Dermatology
• MD Anderson Cancer Center
• Houston, Texas
• 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
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.
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
• Mediated by cytokines & neuropeptides
Class II HLA Genes in AAClass II HLA Genes in AA
• CLASS II MHC (DR,DQ,DP) ASSOCIATIONSCLASS II MHC (DR,DQ,DP) ASSOCIATIONS
– HLA-DR4, DR5 (Italian, Danish, & English); HLA-
– The HLA-DR5 allele *1104-patchy early onset
– 80% of AA have HLA-DQB1*03 alleles
associated with HLA- DR5
MICA alleles assoc with AA – NK receptor
– Welsh/Duvic JID 103: 758,1994
– Colombe/Price JAAD 33:757, 1995
AA in Identical Twins
• 55% concordancy in monozygotic twins.
• More severe in first affected, M>>F.
• All had HLA-DQ 0*302
• Stress was precipitating factor
• No association with CMV
–Jackow & Duvic, JAAD 1998.
Alopecia Areata Registry
• Funded by NIAMS, September 23, 2000
• Self registration for Alopecia Areata via
web or paper-based questionnaire/database
• Blood samples (DNA, serum, LB lines)
from examined confirmed AA patients and
Structure of AA Registry
P a t i e n t s
S a n F r a n c i s c o , C a l i f
D r . V e r a P r i c e
P a t i e n t s
D e n v e r , C o l o r a d o
D r . D a v id N o r r i s , C o P I
P a t i e n t s
P a t i e n t s
M i n n e a p o l is , M i n n .
D r . M . H o r d i n s k y
P a t i e n t s
C o l u m b i a U n i v , N Y C
A . C h r is t i a n o
H o u s t o n - M D A C C
C e n t r a l S it e
D r . M . D u v i c , P I
W e b s it e E n t r y
Q u e s t i o n n a ir e
P a t i e n t e n t r y
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
REGISTRATION on WEB
Print-out, Fill-out, &
Mail or Fax in.
Informed consent &
• 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
Selection for the Second Step
• Single patients examined at site.
• AT/AU for > 1 year
• Patchy persistent AA for > 1 year
• Transient AA for < 6 or < 12 mos. with
• Unrelated Normal controls are just as
important as AA subjects.
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
Second Tier Report 10-14-08
• Total Registrants - 2397 (37% of 1st
Females – 1642 (37%)
Males - 750 (36%)
White - 1791 (36%)
Afr Am - 88 (31%)
Hispanic - 159 (43%)
Asian - 125 (54%)
Second Tier Registrants
by Phenotype Severity
• 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
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
0 10 20 30 40 50 60 70 80
Age of Onset (years)
AGE OF ONSET vs % AA INDIVIDUALS AFFECTED
Age of Onset – AA Registry
• There are two peaks between 1-12 yrs
– First peak genetically influenced
– Second peak environmentally induced
• 57% acquire AA before age 20
• Males develop AA 2.5 yrs earlier than
• AU and AT age of onset earlier compared
to AAP and AAT groups (p<0.0001)
• 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
AA Research Progress
• Confirmed the HLA associations
• Studies of cytokine profiles in AA with or
• 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
No AA: 1,2,3,6 and Yes: 4, 5
Genome - Families
• 20 families -102 affected, 118 unaffected
• US and Israel families
• Susceptibility found on Chromosomes
• 6 –ASP LOD >2.00 several incl MHC
• 16 –ASP/LOD 3.11 – Ps locus
• 18 - LOD 3.93 – Ps Locus
Am J Hum Genet. 2007 Feb;80(2):316-28. Epub 2007 Jan 5.
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 =
• Third: full genome SNP search 1000
AU/AT severe patients, Alumina chip
• Angela Christiano and Peter Griegerson
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
The registry is one room with five desks and lots of filing cabinets
Our laboratory Team is standing by waiting for your samples!!
• 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.
• NIAMS & NAAF for support
• Steering committee and sites: Drs.
Hordinsky, Price, Norris, Christiano
• Advisors: Alan Moshell, Vickie Kalabokas,
Jorge Oxenberg, Kurt Stenn, Lowell
• All of the families, individuals, med
students who have participated to make this
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