LG 1.11 - Autoimmune Muscle Diseases

Question 1

How do inflammatory myopathies appear looking histopathologically?

Answer 1

• Inflammation of endomysium
• muscle fiber necrosis
• fibrosis

Question 2

What is the evidence for the autoimmune nature of inflammatory myopathies?

Answer 2

• Presence of auto-antibodies
• Association with HLA types
• Increased expression of HLA in muscle (would not usually do this)
• Activated T and B lymphocytes in skeletal muscle
• association with other autoimmune diseases
• response to immunotherapies (particularly immunosuppressants)

Question 3

What is 1 important myositis-specific antibody, what does it target?

Answer 3

• Anti-Jo-1

- Targets Amino-acyl tRNA synthetases.

Question 4

What is dermatomyositis?

Answer 4

• inflammatory disease of the muscles accompanied by a skin rash.

Question 5

What are symptoms of dermatomyositis?

Answer 5

• Symmetrical proximal muscle weakness.
• EMG changes
• Elevations of creatine kinase, aldolase, lactate dehydrogenase and transaminases.
• Evidence of chronic inflammation by biopsy
• characteristic rashes
• antibodies to cell constituents

Question 6

What immunopathologic events occur in dermatomyositis?

Answer 6

• Classic or alternative complement activation (“probably secondary to viral and/or bacterial infection”)
• Results in inflammation due to targeting muscle cells/ capillaries (Autoimmune response to muscle cells)
• Can also occur in skin/ capillaries (= rash)

Question 7

What is polymyositis and inclusion body myositis?

Answer 7

• Weakness in muscles near trunk

Question 8

What are the symptoms of polymyositis and inclusion body myositis?

Answer 8

• Proximal muscle weakness

- No rash

Question 9

What are the clinical findings in polymyositis and inclusion body myositis?

Answer 9

• Presence of CD8+ T cells in muscle biopsy
• autoantibodies to amino acyl tRNA synthetases
• HLA class I molecules plus co-stimulatory ligands expressed on muscles.

Question 10

What are the immunopathogenic findings of polymyositis and inclusion body myositis?

Answer 10

• Macrophages are activated by virus
• Macrophages present antigen to CD8+ T cells
• Activated CD8+ T lymphocytes induce pathology by:
  Inflammatory cytokines.
  Release perforin that in turn activates the apoptosis pathway of muscle cells.

Question 11

List the immunologic hallmarks of dermatomyositis:

Answer 11

• Agents activating complement – unknown
• Infiltrating lymphocytes primarily CD4+ and B
• Cytokines, chemokines and adhesion molecules unregulated
• Retrovirus infection may initiate process
• HLA molecules over-expressed in muscles of patients

Question 12

(1) What’s going on in #1?

Answer 12

Complement activated 
(alternate or classical)

Question 13

(1) What’s going on in #2?

Answer 13

C3b, C4b and MAC deposited on endothelium

Question 14

(1) What’s going on in #3?

Answer 14

Capillaries destroyed. Mononuclear cells attracted

Question 15

(1) What’s going on in #4?

Answer 15

Inflammation induced

Question 16

(1) What’s going on in #5?

Answer 16

Chronic inflammation and destruction of muscle fibers causes weakness and pain

Question 17

(2) What’s going on in #1

Answer 17

Macrophages are activated by a virus (or “some” antigen )

Question 18

(2) What’s going on in #2

Answer 18

Activated macrophages present antigen (viral or self) to CD8+ T cells in the context of HLA class I molecules

Question 19

(2) What’s going on in #3

Answer 19

Activated CD8+ T lymphocytes induce pathology by:

1. Inflammatory cytokines, IL-1, IFN-γ and TNF-α
2. IFN-γ induces muscle cells to upregulate genes for co-stimulatory molecules (CD 80/86)
3. Release of perforin that in turn activates the apoptosis pathway