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