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CNSLF Path - Laboratory Dx of Connective Tissue Disorders (i) (Use of lab…
CNSLF Path - Laboratory Dx of Connective Tissue Disorders (i)
Tolerance
failure of immune system to respond to antigen
self-tolerance = don't react to our own tissues
failure of self tolerance results in AI
central T cell tolerance
thymic education
large no of auto reactive T cells die in -ve selection
imperfect process, some leak, hence safety mechanisms in periphery NB + AI common
peripheral T cell tolerance
absence of signal 2/danger signal
active regulation by T regs
B cell tolerance
AI
reactivity: there are measurable autoabs + patient experiencing symptoms
disease: there is enough body destruction to be dxed + loads of potential symptoms
AI arises from many mechanisms
not all known
molecular mimicry
S pharyngitis + rheumatic fever (cardiac muscle attacked)
superantigen
TSS (S Aureus)
Kawasaki disease (blood vessel inflamm most common in under 5s)
tissue develops ability to present antigen
Coxsackie virus insulinitis in T1DM
drugs causing 'altered self'
haemolytic anaemia a/w penicillin allergy
release of sequestered antigen
penetrating eye injury (both eyes attacked - sympathetic ophthalmia)
testicular torsion (both testes attacked)
immune system has never seen these antigens before + hence there's no tolerance
Availability of cryptic epitopes
due to defective cellular debris clearance by macrophages
e.g. SLE
defective immune regulation genes
Use of lab tests
to rule in/out a dx
to monitor disease activity
false +ves + -ves are common
must have well thought out ddx before doing tests
true +ve rate (sensitivity) = % with disease who have -ve test result
true -ve rate (specificity) = % without disease who have -ve test result
false +ve = % without disease who have +ve result
false -ve = % with disease who have -ve test result
PPV = % of those with +ve result who have disease (true +ves divided by all +ves)
critically dependent on disease prevalence in pop tested - hence only test those with signs + symptoms suggestive of disease (inappropriate tests may be misleading)
NPP = % of those with -ve result who don't have disease (true -ves divided by all -ves)
coeliac lab test = v sensitive + specific
impact of indiscriminate testing
false +ve results create anxiety + risk to patient, unnecessary tests, inappropriate tx, delay getting correct tx
cost
delays test results for those who actually have disease
Autoabs
found in many AI disease
presence doesn't imply role in pathogenesis - e.g. Hashimoto's thyroiditis - tissue injury is T cell mediated, but anti-thyroid abs used to dx
useful in dx
CTDs
aka collagen vasc diseases
group of multi system diseases
pathological changes in blood vessels + connective tissue
usually inflamm (lymphocyte + neutrophil infiltration)
common clinical features
immunological abnormalities
many differences
Scleroderma
excess collagen deposition
Polymyositis
Mixed CTD
features of SLE, scleroderma + polymyositis
often 1 predominates
Sjogren's syndrome
lymphocytic infiltrates in lacrimal + salivary glands - dry eyes + mouth
primary Sjogren's can be a/w really aggressive vasculitis