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What’s new in Research:
Genetics and Immunology
of Alopecia Areata
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
Disclosures
Board Member: Dystrophic EB Research Association of America
Scientific Advisory Council Chair: National Alopec...
V. Herbst et al., Eur J Dermatol 16,
537 (Sep-Oct, 2006).
CD4
CD1a
CD8
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
Challenge of Alopecia Areata Pathogenesis:
Collapse of Immune privilege of the Hair Follicle
From Gilhar, Paus & Kalish, J...
Pathways
Costimulatory Pathway
NKG2D axis
Cytokine signaling
Aligned Diseases
Type 1 diabetes
Rheumatoid arthritis
Celiac ...
• How have genetic studies advanced our
understanding of disease
pathogenesis?
• How have genetic studies led to
translati...
Tofacitinib Treatment 4 months
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
New ideas..
• Building a better JAK inhibitor – understanding which
JAKs are important and which are not – as an approach
...
Does the microbiome play a role in
human alopecia areata?
Skin?
Gut?
Analysis of skin and gut
microbiome in AA patients
NO...
The skin microbiota in AA does not show
significant dysbiosis
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
Gut microbiota in AA patients shows
evidence of significant dysbiosisAA
CTRL
*
*
*
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
AA patients show bidirectional dysbiosis the
gut microbiota –
more of some normal bacteria, less of others
NOT
FOR
DISTRIB...
AA patients show bidirectional dysbiosis the
gut microbiota
OTUID Phylum Order Family Genus
871442 Firmicutes Lactobacilla...
Dysbiosis in the relative abundance of Firmicutes
and Bacteroides in different autoimmune processes
• Western diet and ass...
Disease Bacteroides Firmicutes Reference
Cancer immunotherapy
Promoting anti-tumor effect of
CTLA-4 blockade
Enhance CTLA-...
Rebello, et al. ACG Case Rep J (2017)
Two Patients had C. difficile infection (…and alopecia universalis)
and were treated...
PLEASE PLEASE PLEASE…
Get involved
Stay involved
Spread the word
about
RESEARCH STUDIES
clinical, epidemiological, basic
s...
1996
Angela
gets
AA
2016
Ground
Breaking
Year for
AA
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
Acknowledgements
NIAMS 1P30
NIAMS 1P50
AR070588-01
Alexa
Abdelaziz
James Chen Yanne Doucet
Annemieke de
Jong
Joanna Jackow...
Terminou este documento.
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What's New in Research: Genetics and Immunology of Alopecia Areata

Dr. Angela Christiano presented an update on genetic and immunological studies in alopecia areata. Her research is focused on defining the genetic basis of alopecia areata to clarify how the disease develops—a key initial step toward creating novel therapies. Dr. Christiano is the Richard and Mildred Rhodebeck Professor of Dermatology, Genetics and Development, Vice Chair for Basic Science Research in Dermatology, and Director of the Center for Human Genetics at Columbia University.

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What's New in Research: Genetics and Immunology of Alopecia Areata

  1. 1. What’s new in Research: Genetics and Immunology of Alopecia Areata NOT FOR DISTRIBUTION OR REPRODUCTION
  2. 2. Disclosures Board Member: Dystrophic EB Research Association of America Scientific Advisory Council Chair: National Alopecia Areata Foundation Board Member, Secretary-Treasurer: American Hair Research Society Board Member: Douglass College of Rutgers University Research Grant Recipient: Bristol-Myers Squibb Research Grant Recipient: Pfizer Research Collaborations: Bioniz, Novo Nordisk Scientific Advisor, Shareholder, Consultant: Aclaris Therapeutics Consultant: Dermira Co-Founder: Rapunzel Bioscience Past President 2016-2017: Society for Investigative Dermatology NOT FOR DISTRIBUTION OR REPRODUCTION
  3. 3. V. Herbst et al., Eur J Dermatol 16, 537 (Sep-Oct, 2006). CD4 CD1a CD8 NOT FOR DISTRIBUTION OR REPRODUCTION
  4. 4. Challenge of Alopecia Areata Pathogenesis: Collapse of Immune privilege of the Hair Follicle From Gilhar, Paus & Kalish, JCI, 2007 NOT FOR DISTRIBUTION OR REPRODUCTION
  5. 5. Pathways Costimulatory Pathway NKG2D axis Cytokine signaling Aligned Diseases Type 1 diabetes Rheumatoid arthritis Celiac disease Surprises Genome-wide Association Study in AA NOT FOR DISTRIBUTION OR REPRODUCTION
  6. 6. • How have genetic studies advanced our understanding of disease pathogenesis? • How have genetic studies led to translational research and new clinical approaches? NOT FOR DISTRIBUTION OR REPRODUCTION
  7. 7. Tofacitinib Treatment 4 months NOT FOR DISTRIBUTION OR REPRODUCTION
  8. 8. New ideas.. • Building a better JAK inhibitor – understanding which JAKs are important and which are not – as an approach to reduce side effects. • JAK inhibitors may induce “T cell exhaustion” as part of their mechanism of action – can we use this to study relapse – how and when it occurs? • Why do some patients respond to JAK inhibitors and not others? Lessons? What else might AA patients respond to if not JAK inhibitors? • Gut microbiome in AA patients – environmental triggers? New clinical trials of fecal microbiota transplant (FMT). NOT FOR DISTRIBUTION OR REPRODUCTION
  9. 9. Does the microbiome play a role in human alopecia areata? Skin? Gut? Analysis of skin and gut microbiome in AA patients NOT FOR DISTRIBUTION OR REPRODUCTION
  10. 10. The skin microbiota in AA does not show significant dysbiosis NOT FOR DISTRIBUTION OR REPRODUCTION
  11. 11. Gut microbiota in AA patients shows evidence of significant dysbiosisAA CTRL * * * NOT FOR DISTRIBUTION OR REPRODUCTION
  12. 12. AA patients show bidirectional dysbiosis the gut microbiota – more of some normal bacteria, less of others NOT FOR DISTRIBUTION OR REPRODUCTION
  13. 13. AA patients show bidirectional dysbiosis the gut microbiota OTUID Phylum Order Family Genus 871442 Firmicutes Lactobacillales Streptococcaceae Streptococcus 176034 Bacteroidetes Bacteroidales Bacteroidaceae Bacteroides 580008 Firmicutes Erysipelotrichales Erysipelotrichaceae NA 4381430 Firmicutes Clostridiales Ruminococcaceae Faecalibacterium 184876 Firmicutes Clostridiales Lachnospiraceae Lachnospira 752354 Firmicutes Clostridiales Lachnospiraceae Coprococcus 4469233 Firmicutes Clostridiales NA NA 195757 Firmicutes Clostridiales Ruminococcaceae NA 344430 Firmicutes Clostridiales Ruminococcaceae Faecalibacterium 329313 Firmicutes Clostridiales Lachnospiraceae NA 174493 Firmicutes Clostridiales Ruminococcaceae NA 591635 Firmicutes Clostridiales Ruminococcaceae Ruminococcus 195270 Firmicutes Clostridiales Ruminococcaceae NA 192221 Firmicutes Clostridiales Lachnospiraceae NA 4339144 Bacteroidetes Bacteroidales [Odoribacteraceae] Butyricimonas 348009 Firmicutes Clostridiales Ruminococcaceae Oscillospira 325419 Firmicutes Clostridiales Clostridiaceae NA 4365130 Bacteroidetes Bacteroidales Porphyromonadaceae Parabacteroides 310247 Bacteroidetes Bacteroidales Bacteroidaceae Bacteroides NOT FOR DISTRIBUTION OR REPRODUCTION
  14. 14. Dysbiosis in the relative abundance of Firmicutes and Bacteroides in different autoimmune processes • Western diet and associated changes in the gut microbiota drive the increasing incidence of inflammatory diseases. – Increase in Firmicutes and decrease in Bacteroides abundances • Biotin-deficient germ-free mice develop alopecia associated with increase in Firmicutes, especially Lactobacillales. • Gut dysbiosis in IBD patients • Overgrowth of proteobacteria and reduction in Firmicutes and Bacteroides. • Increased Firmicutes translocated from the gut in mice and patients with SLE…gut priming of Tcells and a ‘leaky gut’? • Lower Ruminococcus colonization (firmicutes) is associated with disease in a model of multiple sclerosis (EAE). Maslowsky and Mackay, 2011; Campbell, AW, 2014; Berer et al, 2017; Hayashi et al, 2017; Yadav et al, 2017 NOT FOR DISTRIBUTION OR REPRODUCTION
  15. 15. Disease Bacteroides Firmicutes Reference Cancer immunotherapy Promoting anti-tumor effect of CTLA-4 blockade Enhance CTLA-4 blockade 28 Vitiligo Increase Increase 29 Colorectal Cancer Decrease Decrease 18 IBD Decrease Decrease 15 SLE Decrease Decrease 5 T1D Increase Decrease 15 Autism Spectrum Disorder Increase Decrease 15 Celiac Disease Increase Decrease 30 Scleroderma Decrease Increase 5 MS Decrease Increase 16 Grave's Disease Decrease Increase 5,31 AA Decrease Increase Patterns of dysbiosis in firmicutes and bacteroides in other autoimmune diseases NOT FOR DISTRIBUTION OR REPRODUCTION
  16. 16. Rebello, et al. ACG Case Rep J (2017) Two Patients had C. difficile infection (…and alopecia universalis) and were treated with Fecal Microbiota Transplant (FMT) Clinical Trial to begin 3Q18 NOT FOR DISTRIBUTION OR REPRODUCTION
  17. 17. PLEASE PLEASE PLEASE… Get involved Stay involved Spread the word about RESEARCH STUDIES clinical, epidemiological, basic science…YOU are the most important part of what we do!! NOT FOR DISTRIBUTION OR REPRODUCTION
  18. 18. 1996 Angela gets AA 2016 Ground Breaking Year for AA NOT FOR DISTRIBUTION OR REPRODUCTION
  19. 19. Acknowledgements NIAMS 1P30 NIAMS 1P50 AR070588-01 Alexa Abdelaziz James Chen Yanne Doucet Annemieke de Jong Joanna Jackow Zhenpeng Dai Avi Bitterman Jung U Shin Zongyou Guo Brigitte Sallee Liang Liu Adriana Figueroa Carey Kim Lynn Petukhova Ashley Kwon Christina Tejeda Mei Mei Li Corey Hansen Eddy Wang Rolando Perez- Lorenzo Dominic Delorenzo Etienne Wang Rupali Gund Federica Magrelli Gwennaelle Monnot Ryota Hayashi Maria Gnarra Hasan Erbil Abaci Stephanie Erjavec NCATS UH2TR002090 NIAMS R01AR065963 NOT FOR DISTRIBUTION OR REPRODUCTION
  • TomokoMaedaChubachi

    Sep. 14, 2020
  • TomokoMaedaChubachi

    Sep. 14, 2020

Dr. Angela Christiano presented an update on genetic and immunological studies in alopecia areata. Her research is focused on defining the genetic basis of alopecia areata to clarify how the disease develops—a key initial step toward creating novel therapies. Dr. Christiano is the Richard and Mildred Rhodebeck Professor of Dermatology, Genetics and Development, Vice Chair for Basic Science Research in Dermatology, and Director of the Center for Human Genetics at Columbia University.

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