Immunology 8 - Autoimmunity (ii)
Rheumatic fever
acute inflamm systemic illness
occurs 2-4 wks after a group A beta-haemolytic strep PHARYNGITIS
molecular mimicry - destructive inflamm lesions on heart myocardium/valves, articular structures (synovial joints), neurons
IgG deposition, but gone once strep removed
fever
migrating carditis
chorea
lymphocytic infiltration destroys normal branched muscle fibres
Dx = Jone's criteria (clinical is best)
major symptoms
carditis
polyarthritis (multiple joints)
erythema marginatum
mild pink rings, not sure or itchy
subcut nodules
minor symptoms
fever
arthralgia (joint pain without clear inflamm/swelling)
Hx of rheumatic fever (can get recurrences)
evidence of strep infection
longterm sequelae
valvular heart disease
endocarditis (increased risk)
persistent chorea
Mechanisms of tissue injury
type 2 hypersensitivity: humoral immunity
type 3 hypersensitivity: immune complex deposition
type 4 hypersensitivity: cellular immunity
indirect Ig effects
Lab tests
rule in/out a Dx
can monitor disease progression/activity
false +ves + -ves common
sometimes a clinical Dx is best
can also look for anti-streptolysin ig in lab
sensitivity
% of people with Dx detected by test
true +ves / all cases (true +ves + false -ves)
specificity
% of people without Dx with a -ve test
true -ves / all non cases (true -ves + false +ves)
PPV
% of +ve tests that actually have Dx
true +ves / all +ves (true + false)
NPV
% of -ve tests that actually don't have Dx
true -ves / all -ves (true + false)
depends on chosen cut-off + disease prevalence in pop
depends on chosen cut-off (not so much prevalence)
if high, a -ve test can rule out a Dx
PPV + NPV good for assessing performance of a diagnostic test
low cut-off - sensitive but not specific (more false +es)
high cut-off - specific but not sensitive (more false -ves)
diagnostic efficacy
% of people correctly classified by the test
all true results / all results (true and false)
impact of indiscriminate (not marked by careful distinction) testing
false +ves create anxiety, unnecessary further testing, inappropriate Tx, delay in getting correct Dx
costly
delays results for true +ves
detection of autoIgs
agglutination assays
indirect immunofluorescence
ELISA (enzyme-linked immunosorbent assay)
coat beads with antigen of interest + put them in serum sample
if Ig present agglutination occurs (bridges between beads)
v rapid
add antigen to serum sample + wash
if present Ig will bind to antigen + hence not wash away
add fluorescently-labelled anti-human Ig + wash
labour intensive
subjective unless strongly +ve or -ve
known concs of antigen + autoIg in serum + anti-human Ig = colour change
not subjective - colour intensity read by computer + numerical value given