Immuno: Autoinflammatory and Autoimmune diseases Pt.4

Question 1

What are some clincial features of anti-phospholipid syndrome

Answer 1

Triad

• recurrent arterial or venous thrombosis
• recurrent miscarriages
• thrombocytopenia

Livedo reticularis on skin

Can occur alone or secondary to SLE

Question 2

Which antibodies are tested for in antiphospholipid syndrome?

Answer 2

• Anti-cardiolipin - immunoglobulins directed against phospholipids (also positive in syphilis)
• Anti-beta2 glycoprotein-1 - antibody specific for glycoprotein found associated with negatively charged phospholipids
• Lupus anticoagulant - prolongation of phospholipid-dependent coagulation tests (in vitro phenomenon)

NOTE: lupus anticoagulant cannot be assessed if the patient is on anticoagulant therapy

NOTE: all three tests should be performed as 40% of patients have disconcordant antibodies

Question 3

What is the pathophysiology of Sjorgren’s syndrome?

Answer 3

Autoimmune destruction of exocrine glands

Question 4

What autoantibodies are positive in Sjogren’s?

Answer 4

Anti-Ro and Anti-La

Question 5

Which malignancy are patients with Sjogrens at risk of developing

Answer 5

Mucosa Associated Lymphoid Tissue Lymphoma

Question 6

Outline the pathophysiology of systemic sclerosis.

Answer 6

Cytokines released by Th2 and Th17 leads to activation of fibroblasts and the development of fibrosis

NOTE: polymorphisms in type I collagen alpha 2 chains, fibrillin 1 and TGF-beta may be implicated

Cytokines can also activate endothelial cells and contribute to microvascular disease

Question 7

What are the main features of limited cutaneous systemic sclerosis?

Answer 7

Calcinosis

Raynaud’s phenomenon

Esophageal dysmotility

Sclerodactyly

Telangiectasia

NOTE: also pulmonary hypertension

Question 8

What are the main features of diffuse cutaneous systemic sclerosis?

Answer 8

• Skin involvement extends beyond the forearms
• CREST features
• More extensive gastrointestinal disease
• Interstitial pulmonary disease
• Renal cysts / failure

Question 9

Which antibodies are seen in limited and diffuse cutaneous systemic sclerosis?

Answer 9

Limited - anti-centromere

Diffuse - anti-topoisomerase (aka anti-Scl70)

Question 10

Describe the differences between the histology of dermatomyositis and polymyositis.

Answer 10

• Dermatomyositis - perivascular CD4+ T cell and B cells are seen, this can cause an immune complex-mediated vasculitis (type III response)
• Polymyositis - CD8+ T cells surround HLA Class I expressing myofibres, CD8+ T cells kill these myofibres via granzyme/perforin (type IV response)

Question 11

What are some cutaneous features of dermatomyositis

Answer 11

• Heliotrope rash
• Gottron papules
• Photosensitivity

Question 12

What are some diagnostic investigations in inflammatory myopathies

Answer 12

• Bloods
  
  • Raised CK
  • ANA
• EMG
• Muscle biopsy (gold standard)

Question 13

What key symptoms differentiates inflammatory myopathies from PMR

Answer 13

Muscle weakness only present in inflammatory myopathies not PMR

Question 14

Which antibodies are seen in dermatomyositis and polymyositis?

Answer 14

• ANA positive (in some patients) - ask for extended myositis panel
• Dermatomyositis: anti-aminoacyl tRNA synthetase (e.g. Jo-1), anti-Mi2
• Polymyositis: anti-aminoacyl tRNA synthetase antibody is cytoplasmic

Question 15

If ANA is positive, which ANA subtypes indicate which type of disease

Answer 15

Question 16

Which classification system is used for systemic vasculitides?

Answer 16

Chapel Hill

Question 17

What does ANCA stand for

Answer 17

Anti-neutrophil cytoplasmic antibodies

Question 18

Which small vessel vasculitides are associated with ANCA?

Answer 18

• Microscopic polyangiitis (pANCA)
• Eosinophililc Granulomatosis with polyangiitis (pANCA)
  aka Churg-Strauss syndrome
• Granulomatosis with polyangiitis (cANCA)

Question 19

Outline the pathophysiology of ANCA.

Answer 19

• These antibodies are specific to antigens located within the cytoplasm of neutrophils
• Inflammation may lead to expression of these antigens on the surface of neutrophils
• Antibody engagement with these antigens may lead to neutrophil activation (type II hypersensitivity)

NOTE: these are different from anti-nuclear antibodies

Question 20

Describe the key difference between cANCA and pANCA.

Answer 20

cANCA

• Cytoplasmic fluorescence
• Associated with antibodies against proteinase 3
  Occurs in >90% of GPA patients with renal involvement (wegeners)

pANCA

• Perinuclear staining pattern
• Associated with antibodies to myeloperoxidase
• Associated with MPA and EGPA (Churg-Strauss syndrome)
• Less sensitive and specific than cANCA