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.
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
What's New in Research: Genetics and Immunology of Alopecia Areata
1. What’s new in Research:
Genetics and Immunology
of Alopecia Areata
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
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. V. Herbst et al., Eur J Dermatol 16,
537 (Sep-Oct, 2006).
CD4
CD1a
CD8
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
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. 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. • 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
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. 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. The skin microbiota in AA does not show
significant dysbiosis
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
11. Gut microbiota in AA patients shows
evidence of significant dysbiosisAA
CTRL
*
*
*
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
12. AA patients show bidirectional dysbiosis the
gut microbiota –
more of some normal bacteria, less of others
NOT
FOR
DISTRIBUTION
OR
REPRODUCTION
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. 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. 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. 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. 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
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