National Alopecia Areata
Registry
• Madeleine Duvic, MD
• Professor of Medicine & Dermatology
• MD Anderson Cancer Center
...
Investigators
• Angela Christiano – Columbia, NYC
• Maria Hordinsky – Univ of Minnesota
• David Norris – Univ of Colorado
...
Purpose of the AA Registry
• 1. To find and collect samples from
multiplex families, siblings, and individuals
with alopec...
HYPOTHESIS:
Alopecia Areata is
• Genetic - Host determined, HLA restricted
• Organ specific T-cell mediated directed to
th...
Class II HLA Genes in AAClass II HLA Genes in AA
• CLASS II MHC (DR,DQ,DP) ASSOCIATIONSCLASS II MHC (DR,DQ,DP) ASSOCIATION...
AA in Identical Twins
• 55% concordancy in monozygotic twins.
• More severe in first affected, M>>F.
• All had HLA-DQ 0*30...
Alopecia Areata Registry
• Funded by NIAMS, September 23, 2000
• Self registration for Alopecia Areata via
web or paper-ba...
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...
Registration is Two Steps
• Step One: US AA patients confirmed by
dermatologist asked to fill out short form.
(Web, Doctor...
AlopeciaAreataRegistry.orgAlopeciaAreataRegistry.org
REGISTRATION on WEB
or
Print-out, Fill-out, &
Mail or Fax in.
Brochur...
Informed consent &
confidentiality
• Patients sign 3 written consents to
participate in step 2 of the registry.
• Descript...
Selection for the Second Step
• Single patients examined at site.
• AT/AU for > 1 year
• Patchy persistent AA for > 1 year...
Real time report:
First Tier Registration 10-14-08
• Total individuals registered - 6,469
Females 4,399 vs Males 2,070
• R...
Second Tier Report 10-14-08
• Total Registrants - 2397 (37% of 1st
tier)
Females – 1642 (37%)
Males - 750 (36%)
White - 17...
Second Tier Registrants
by Phenotype Severity
Phenotype
• Transient AA (AAT) 306
• Persistent Patchy AA (AAP) 485
• Alopec...
AA Registry Goals
• 1000 AU and AT (859)
• 500 AAP (persistent) (485)
• 250 AAT (transient) (183)
• ANOVA, Generalized Lin...
0
1
2
3
4
5
6
7
8
0 10 20 30 40 50 60 70 80
Age of Onset (years)
PercentageofIndividualsAffected(%)
AU
AT
AAP
AAT1&2
AGE O...
Age of Onset – AA Registry
• There are two peaks between 1-12 yrs
and 25-35yrs
• Speculation:
– First peak genetically inf...
• 57% acquire AA before age 20
• Males develop AA 2.5 yrs earlier than
Females
• AU and AT age of onset earlier compared
t...
AA Research Progress
• Confirmed the HLA associations
• Studies of cytokine profiles in AA with or
without atopy.
• Case C...
Multiplex Family
No AA: 1,2,3,6 and Yes: 4, 5
44,55
1,1,55
AU
AA
44,,55
44,55
AA
AU
1,2
1,4 5,63,4
1,3
3,6 2,4
2,3 4,6
Genome - Families
• 20 families -102 affected, 118 unaffected
• US and Israel families
• Susceptibility found on Chromosom...
Genome Wide Search
• First: screen of SNPs associated with other
autoimmune disease genes.
• Second: Assessment of genetic...
Other Planned Studies
• Case Control Study– associations with
asthma, autoimmune disease
• Second study in identical twins...
The registry is one room with five desks and lots of filing cabinets
Our laboratory Team is standing by waiting for your samples!!
Conclusions
• AAR is a prototype of a web-based, patient
friendly patient REGISTRY at five
cooperating institutions (and I...
Acknowledgements
• NIAMS & NAAF for support
• Steering committee and sites: Drs.
Hordinsky, Price, Norris, Christiano
• Ad...
Alopecia Areata Registry Model
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Transcript of "Alopecia Areata Registry Model"

  1. 1. National Alopecia Areata Registry • Madeleine Duvic, MD • Professor of Medicine & Dermatology • MD Anderson Cancer Center • Houston, Texas
  2. 2. 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
  3. 3. 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.
  4. 4. 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.
  5. 5. 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- DR7 (Russians) – 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
  6. 6. 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.
  7. 7. 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.
  8. 8. 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 REFER By local Dermatologist
  9. 9. 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
  10. 10. AlopeciaAreataRegistry.orgAlopeciaAreataRegistry.org REGISTRATION on WEB or Print-out, Fill-out, & Mail or Fax in. Brochures available
  11. 11. 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
  12. 12. 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 complete regrowth • Unrelated Normal controls are just as important as AA subjects.
  13. 13. 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
  14. 14. 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%)
  15. 15. Second Tier Registrants by 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
  16. 16. 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
  17. 17. 0 1 2 3 4 5 6 7 8 0 10 20 30 40 50 60 70 80 Age of Onset (years) PercentageofIndividualsAffected(%) AU AT AAP AAT1&2 AGE OF ONSET vs % AA INDIVIDUALS AFFECTED
  18. 18. 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
  19. 19. • 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 (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
  20. 20. 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
  21. 21. Multiplex Family No AA: 1,2,3,6 and Yes: 4, 5 44,55 1,1,55 AU AA 44,,55 44,55 AA AU 1,2 1,4 5,63,4 1,3 3,6 2,4 2,3 4,6
  22. 22. 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.
  23. 23. 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
  24. 24. 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
  25. 25. The registry is one room with five desks and lots of filing cabinets
  26. 26. Our laboratory Team is standing by waiting for your samples!!
  27. 27. 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.
  28. 28. Acknowledgements • 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. AlopeciaAreataRegistry.org mduvic@mdanderson.org
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