Immunology of multiple sclerosis: clinical

Question 1

What are the 4 phases of the evolution of multiple sclerosis?

Answer 1

1. Tiggers preceding CNS inflammation
2. Preclinical activity
3. Relapsing-remitting MS
4. Progressive MS

Question 2

What are the 3 diagnostic tools for multiple sclerosis research?

Answer 2

1. Blood samples: DNA, cellular immunology and serum (biomarkers)
2. Cerebrospinal fluid: cellular immunology and biomarkers
3. Neuroradiology: MRI, etc.

Question 3

What is the major genetic risk factor for multiple sclerosis, what is it associated to and how does it affect B-cells?

Answer 3

• HLA-DRB1*15 haplotype causes autoimmunity
• Associated with increased auto-proliferation of T-cells (mainly Th1)
• Auto-proliferating B-cells drive activation of CD4+ T-cells in a HLA-DR-dependent manner

Question 4

How does Natalizumab treat multiple sclerosis?

Answer 4

It is antibodies blocking cells to infiltrate into the brain through the blood-brain-barrier, but severe relapse when patients stop treatment

Question 5

Which cytokine is the most abundant in increased multiple sclerosis?

Answer 5

IFN-γ (induces Th1)

Question 6

What is the association between EBV and MS?

Answer 6

EBV causes epigenetic changes in B-cells making them more prone to induce auto-reactivity

Question 7

How is the auto-reactive CD4+ T-cell repertoire maintained in the periphery?

Answer 7

Perturbed homeostasis: 
• reduced thymic output
• alterations in Treg
• reduced TCR diversity
• signature for cell proliferation

Question 8

What type of treatment for MS is promising regarding B-cells?

Answer 8

B-cell depleting treatment is effective against MS:

• reduces auto-proliferation and IFN-γ response of T-cells (in vitro)
• reduces significantly activated CD4+ T-cells (in vivo)

Question 9

What does research show regarding if MS is an autoimmune disease or neurodegeneration disease?

Answer 9

Genetic factors and treatment mechanisms point towards an autoimmune cause that secondarily drives neurodegeneration