Global Down Syndrome Foundation Webinar Series | Global Down Syndrome Foundation

Global Down Syndrome Foundation Webinar Series

FALL 2016

Autoimmune Disorders and Down Syndrome:

What you need to know

SUMMARY

What is the connection between Down syndrome and autoimmune diseases? Will everyone with Down syndrome develop an autoimmune disease? Can studying people with Down syndrome lead to progressive understanding of diseases affecting the typical population?

Two Internationally-renowned scientists – Richard Spritz, MD, Program Director of the University of Colorado School of Medicine Human Medical Genetics & Genomics Program and 2013 Linda Crnic Institute Grand Challenge Grant Recipient and Joaquín Espinosa, PhD, Associate Director for Science at the Linda Crnic Institute for Down Syndrome at the University of Colorado School of Medicine, Associate Professor of Molecular, Cellular and Developmental Biology at University of Colorado BoulderCo-Leader of the Molecular Oncology Program at University of Colorado Cancer Center, and Director of the Functional Genomics Facility at CU Boulder, have covered these questions and more.

SPEAKERS & PRESENTATIONS

Richard Spritz, M.D.

2013 Linda Crnic Institute Grand Challenge Grant Recipient

Program Director of the University of Colorado School of Medicine Human Medical Genetics & Genomics Program

“Genetic Role of UBASH3A in Autoimmune Disease in Down Syndrome”

Joaquin Espinosa, PhD.

Associate Director for Science at the Linda Crnic Institute for Down Syndrome at the University of Colorado School of Medicine

Associate Professor of Molecular, Cellular and Developmental Biology at University of Colorado Boulder

Co-Leader of the Molecular Oncology Program at University of Colorado Cancer Center

Director of the Functional Genomics Facility at CU Boulder

“Understanding Down Syndrome as an Interferonopathy”

Q&A

Q: How do I determine if my child has an autoimmune disease? What are the symptoms?

Q: What is the effect of diet on development of autoimmune disorders in people with DS?

A: There is no known relationship of diet to development of autoimmune disorders

Q: With the "symptoms" of thyroid disease & Down syndrome so similar, why is TSH not treated at a lower high-threshold than the typical population?

A: The diagnostic criteria of autoimmune thyroid disease are the same in people with Down Syndrome and in the general population. Inappropriate treatment of people with normal TSH would inappropriately function of a normal thyroid.

Q: When do you anticipate the Interferon drugs to be available for use and when do you also estimate broadening their use for other conditions? What is the next step in using drugs to block interferon hypersensitivity? Is there a next research study looking at the efficacy of specific drugs?

A: Different classes of ‘Interferon antagonists’ are already FDA-approved for specific medical conditions, such as polycythemia vera, myelofibrosis and rheumathoid arthritis. Information about these drugs can be found at the following links:

http://www.jakafi.com

https://en.wikipedia.org/wiki/Tofacitinib

http://ra.xeljanz.com/

These drugs are being tested for other conditions, such as psoriasis and alopecia areata. More information about these ongoing efforts can be found at the following links:

http://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_oral_tofacitinib_meets_primary_endpoints_in_pivotal_phase_3_psoriasis_trials

http://www.pharmaceutical-journal.com/news-and-analysis/features/finding-new-treatments-for-alopecia-areata-patients/20201092.article

With regards to potential use of these drugs for ameliorating other ill effects of trisomy 21, there is much pre-clinical research that needs to be performed, and the timeline can not be estimated at this point. The next steps are to test the effect of dampening Interferon signaling in animal models of Down syndrome.

Q: What are the most common autoimmune diseases affecting people with T21? Is there some sort of statistical graph I can look at?

A: Autoimmune thyroid disease (Hashimoto’s disease/hypothyroid ism and Graves’ disease/hyperthyroidism) ~35%; Celiac disease 1.4-5 %; Vitiligo ~3%; type 1 diabetes mellitus ~1%; rheumatoid arthritis ~ 0.87%.

Q: Dr. Spritz: Recently, many people are treating children with DS for thyroid conditions based on newer, less-tested methods where reverse T3 is measured regardless of whether TSH and T4 blood levels are within normal ranges, which is how thyroid dysfunction is currently tested by the Sie Center for DS and is the current testing methodology in the medical community. If the incidence of thyroid disease is actually much higher in DS community than currently accepted testing measures indicate, what might that mean to your study results or expectations regarding UBASH3A function?

A: Reverse T3 is not an accepted valid diagnostic test for thyroid disease. Most reverse T3 in fact is made outside of the thyroid gland and is not reflective of thyroid disease.

Q: Wouldn't treatment to reduce interferon responsiveness increase a DS individual's susceptibility to serious viral infections?

A: This is correct. Increased susceptibility to certain infections are listed among the possible side effects of interferon antagonist treatment (see weblinks on #3 above for more information).

Q: My child has normal thyroid and blood work but premature hair loss. What treatments are there for this?

A: You should consult a pediatric dermatologist.

Q: Do people with Ds get arthritis? How can I tell if my adult child has a high threshold for pain and can’t communicate well?

A: Yes. Anyone can get osteoarthritis. The frequency of rheumatoid arthritis in people with Down syndrome is estimated at ~0.87%.  If you are concerned about possible arthritis, you should consult a rheumatologist.