Multiple SclerosisEmily FergDNA Diagnostic Lab

Multiple Sclerosis (MS) - What is it?

1. Immune-Mediated Processa. Degradation of the myelin sheath around nerves in the Central Nervous System

(CNS)

b. Not considered “autoimmune” since the exact antigen attacked by the body’s immune system remains unknown

c. Damaged myelin results in scar tissue (sclerosis)

d. Nerve signals are disrupted due to damaged oligodendrocytes, axon

MS - What Causes It?

1. Unknowna. Environmental Factors

b. Genetics

c. Infectious Agents

2.What doesn’t cause ita. Having pets

b. Aspartame

c. Experiencing physical trauma(see “A. Siva, MD, K. Radhakrishnan, MD, L. T. Kurland, MD, DrPH, P. C. O’Brien, PhD, J. W. Swanson, MD, and M. Rodriguez, MD. ‘Trauma and multiple sclerosis.’ Neurology: October 1993 vol. 43. doi: http://dx.doi.org/10.1212/WNL.43.10.1878”, “W A Sibley, C R Bamford, K Clark, M S Smith, J F Laguna. ‘A prospective study of physical trauma and multiple sclerosis.’ Journal of Neurology, Neurosurgery & Psychiatry: 1991 vol. 54 issue 7. doi: 10.1136/jnnp.54.7.584”, “D.S. Goodin, MD, G.C. Ebers, MD, K.P. Johnson, MD, M. Rodriguez, MD, W.A. Sibley, MD, and J.S. Wolinsky, MD. ‘The relationship of MS to physical trauma and psychological stress.’ Neurology: June 1999 vol. 52. doi: http://dx.doi.org/10.1212/WNL.52.9.1737”)

MS - Types of MS

1.Clinically Isolated Syndrome (CIS)

2.Relapsing-Remitting MS (RRMS)

3.Primary Progressive MS (PPMS)

4.Secondary Progressive MS (SPMS)

MS - Relapsing-remitting MS

MS - Primary Progressive MS

MS - Secondary Progressive MS

MS - How do I know if I have it?

1.MRI

2.Evoked Potentials (particularly visual evoked potentials)

3.Blood Tests

4.Testing for:a. Mental, emotional, and language functions

b. Movement, coordination, and balance

c. Sensory responses

5.Eye Exam (not an accepted clinical diagnosis)

MS - Not a Mendelian Disorder

Mendelian Disorders

- Controlled by a single gene

Complex Disorders

- Multiple genes in combination with lifestyle and environment

MS - The Genes Behind It

1.HLA-DRB1

2.CYP27B1

3.IL2RA

4.IL7R

MS - HLA-DRB1

- Part of MHC Class II

- Beta chain of the HLA-DR antigen-binding heterodimer

- Over 400 different alleles, each with varying implications of disease severity

MS - CYP27B1

- 25-hydroxy-vitamin D-1 alpha hydroxylase

- Studies have shown that MS patients have lower levels of active D3 (See “Smolders J, Damoiseaux J, Manheere P, and Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J. Neuroimunol 2008; 194; 7-17”)

- Also correlates with the observation that %population with MS increases with increasing latitude

MS - IL2RA

- Key role in differentiation of CD4 and CD25 regulatory T cells

- +50704 in the 3’ UTR

- More prevalent in RRMS patients

MS - IL7R

- Found in B and T cells and is vital for the development and survival of T lymphocytes

- Membrane-bound vs. soluble

- Exon 6 (T244I variant)

Having fun with MS Awareness

- WVU #RunningManChallenge (https://www.youtube.com/watch?v=c3WphKFJ1g4)

- 2016 World MS Day: May 25

- 2016 MS Awareness Week: Mar. 7-13

References1. Sundqvist E, Baarnhielm M, Alfredsson L, Hillert J, Olsson T, and Kockum I. Confirmation of association between multiple sclerosis

and CYP27B1. European Journal of Human Genetics (2010); 18: 1349-1352.2. http://www.nationalmssociety.org/3. https://www.nlm.nih.gov/medlineplus/ency/article/003631.htm4. https://ghr.nlm.nih.gov/primer/mutationsanddisorders/complexdisorders5. http://multiple-sclerosis-research.blogspot.com/2015/01/education-whats-mri.html6. http://www.mult-sclerosis.org/howms.html7. Oksenberg J R, Baranzini S E, Sawcer S, and Hauser S L. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis.

Nature Reviews (2008); 9: 516 - 526.8. Metcalfe, Su M. One protein, two healing properties. Nature News and View (2011); 477: 287-288.9. Matesanz F, Caro-Maldonado A, Fedetz M, Fernandez O, Milne R L, Guerrero Mi, Delgado C, and Alcina A. IL2RA/CD25

polymorphisms contribute to multiple sclerosis susceptibility. Journal of Neurology (2007); 254: 682 - 684.