Similarities Between

Type 1 Diabetes and Alopecia Areata

Alopecia Areata Research Summit 2016

Teresa DiLorenzo, Ph.D.

Microbiology and Immunology

Medicine (Endocrinology)

Einstein-Mount Sinai Diabetes Research Center

Diane Belfer, Cypres & Endelson Families

Faculty Scholar in Diabetes Research

Organ-specific Autoimmune Diseases

Type 1 diabetes Alopecia areata

Dermatol Ther (2011) 24:369

Patchy Nature of Disease

Diabetes (2016) 65:719

Type 1 diabetes Alopecia areata

N Engl J Med (2012) 366:16

13 y.o. with type 1 diabetes for 5 years

Similar Prevalence

BMC Medicine (2013) 11:73

Incidence is Increasing

Type 1 diabetes

Pediatr Diabetes (2007) 8 (Suppl 6):6

Alopecia areata

Cumulative

lifetime incidence

1975-1989 1.7%

1990-2009 2.1%

(Olmstead County, MN)

Mayo Clin Proc (1995) 70:628

J Invest Dermatol (2014) 134:11411990-1999

Shared Gene Associations

Genes Associated with Alopecia Areata

Nature (2010) 466:113

Increased risk for type 1 diabetes in relatives of patients with alopecia areata

Am J Med Genet (1994) 51:234

Associations of Autoimmune Diseases

in Relatives

Proband’s disease Diseases in relatives

Type 1 diabetes Autoimmune thyroid disease

Psoriasis

Rheumatoid arthritis

Vitiligo

Alopecia areata Autoimmune thyroid disease

Psoriasis

Type 1 diabetes

Vitiligo

BMC Medicine (2013) 11:73

Expression of Associated Genes

in the Target Organ

Diabetes, 2010, 59:1561

Type 1 diabetesAlopecia areata

ULBP3

STX17

PRDX5

Nature (2010) 466:113

Importance of CD8 T Cells

J Exp Med (2012) 209:51

Type 1 diabetes

Required in rodent models

Observed in the target organ

Alopecia areata

Nature (2010) 466:113

Required in rodent models

Observed in the target organ

Human

T cells

lentiviral

transduction

Human islet-

reactive T cells

Effect on T cells?

Effect on disease?

Diabetes?

NOD.scid.IL2rγnull

HLA-A2

(NSG-A2)

Human T cell receptors

specific for IGRP 265-273

presented by HLA-A2

2AT cell receptor a chain T cell receptor b chain

5’ LTR SFFV promoter 2A GFP 3’ LTR

Mouse Models Incorporating Human T Cells

Human

T cells

lentiviral

transduction

Human islet-

reactive T cells

Effect on T cells?

Effect on disease?

Diabetes?

NOD.scid.IL2rγnull

Ab0 HLA-DR4

(NSG-Ab0-DR4)

Human T cell receptors

specific for GAD 555-567

presented by HLA-DR4

2AT cell receptor a chain T cell receptor b chain

5’ LTR SFFV promoter 2A GFP 3’ LTR

Mouse Models Incorporating Human T Cells

Conclusion

Given the striking similarities between type 1 diabetes and alopecia areata,

collaboration between the fields should yield abundant benefits.