Immune-mediated disease in clinical practice – an overview

Question 1

Trigger factors

Answer 1

release of sequestered antigens
abnormal immunoregulation
molecular mimicry
polyclonal activation of T and B cells
exposure of cryptic epitopes, or haptenisation of foreign molecules to self antigens

Question 2

Role of infection

Answer 2

Break-down of vascular or cellular barriers - exposure of self-antigens
cell death by necrosis - infl
Polyclonal activation of T cells - bacterial superantigens
Molecular mimicry - cross-reactivity

Question 3

Aetiology

Answer 3

unclear in many autoimmune diseases

Genetic, infectious and hormonal influences

Question 4

History and physical exam.

Answer 4

remission and exacerbation
Lameness, mucocutaneous lesions, lethargy, dyspnoea, weight loss, PU/PD, ± seizures or behavioural changes
Effusive, painful joints; cutaneous erythema, macules, papules, pustules, erosion etc; pallor ± petechiae; cardiac arrhythmias; lymphadenomegaly ± splenomegaly

Question 5

Diagnostic tests: CBC/coags - results

Answer 5

Anaemia - Regenerative (IMHA), or non (infection,
uraemia, chronic bleeding, attack of precursors)
Thrombocytopaenia - immune-mediated (I-M) thrombocytopaenia
Leucopaenia? - Anti-leucocyte antibodies (eg. Systemic lupus erythematosus SLE, I-M neutropaenia)
Coagulation abnormalities - ↑ APTT, PT: ‘anticoagulant antibody’ (SLE), DIC

Question 6

Diagnostic tests: chem. panel - Azotaemia, ↑ inorganic phosphate - cause

Answer 6

Chronic glomerular lesions

Question 7

Diagnostic tests: chem. panel - Hypoalbuminaemia, hypercholesterolaemia - cause

Answer 7

Protein-losing nephropathy (PLN)

Question 8

Diagnostic tests: chem. panel - Hyperbilirubinaemia - cause

Answer 8

Pre-hepatic / haemolysis

Question 9

Diagnostic tests: chem. panel - Hyperglobulinaemia - cause

Answer 9

Infl disease, polyclonal B cell activation

Question 10

Diagnostic tests: chem. panel - ↑ Creatine kinase and lactate dehydrogenase- cause

Answer 10

Polymyositis and / or myocarditis

Question 11

Diagnostic tests: urinalysis

Answer 11

Proteinuria

Haematuria, pyuria, erythrocyte casts

Question 12

Radiography & arthrocentesis

Answer 12

Joint lesions common in polysystemic I-M disease
Erosive lesions suggest overlap syndrome
Arthritis is not always clinically obvious
Synovial fluid: ↑ WBC, ↑ proportion of neutrophils ± ↑ protein content, with ↓ viscosity + poor mucin clot formation

Question 13

Coombs’ test

Answer 13

If acute IMHA suspected - agglutination + osmotic fragility tests performed
Antibodies associated with surface of RBCs detected with the Coombs’ test
Primary reagent: polyvalent anti-dog or anti-cat
IgG, IgM & C3 antiserum (direct antiglobulin test)
False positive and negative reactions may occur

Question 14

Myasthenia gravis

Answer 14

auto-immune destruction of acetylcholine receptors at synapses
muscle weakness + atrophy

Question 15

Antinuclear antibodies (ANA)

Answer 15

Serum ANA – hallmark of human, canine and feline SLE
Indirect immunofluorescence or immuno-peroxidase test
False positives and false negatives may occur