diagnosis of autoimmune disease Flashcards
what should the immune system be?
tolerant to self antigens - should not identify them as something that needs to be attacked, and those that do need to be eliminated at checkpoints throughout development
how do we detect when there is no self tolerance?
various laboratory tests will identify when there is autoantibodies in the patient’s blood directly against their own antigens and resulting in autoimmune conditions
what is scleroderma?
it is fatigues, aches and pains, and thickening of the skin on the hands and changes to the skin around the mouth - sclerodactyl is thickening of skin on hand making it hard to bend fingers and livedo reticualris is the rash which are two characteristics as well as cold extremities - diffuse systemic sclerosis
how would you diagnose scleroderma?
clinical diagnosis is based on signs and symptoms but to confirm need testing - ANA - antinuclear antibodies, ANCA, CJ to make sure no muscle breakdown, rheumatoid factor, anti CCP AB, complement, FBS, LFTs, U and Es and CRP
what does SCL show?
diffuse systemic sclerosis
what is the aim of diagnostic tests?
not for screening but to answer specific questions or support a clinical diagnosis - do bare minimum so not to confused disease and on right population so that there is a greater ability to differentiate between health and disease
what is sensitivity?
how good a test is at identifying those who actually have the disease - PPV is the proportion of those with positive result that actually have the disease
what is specificity?
it is a measure of how goof the test is at correctly defining people without the disease, therefore NPV is the proportion of people with a negative test who do not have the disease
what happens if you move the cut off of a test to the left?
reduces chance of false negative - loose sensitivity and vice versa
what are non specific diagnosis tests?
inflammatory markers - ESR, CRP, ferritin, fibrinogen, haptoglobin, albumin and complement
what are specific disease tests?
autoantibody testing and HLA typing
what are ANA?
they are antinuclear antibodies - they are antibodies in the patient’s blood that bind to the cell nucleus - can identify which type of AB bind to which part
what is the basic of detection of ANA?
primary reaction by adding serum to large cell, secondary reaction with labelled flurochrome, and then macroscopic examination through indirect immunofluorescence
how can you detect different diseases in ANA detection?
different diseases have different patterns of binding
what is the basics of an immunoblot?
add a blot to a strip of paper and see the colour change, can also use individual ELIZA’s - can detect over 100 different ABs of SLE
what is the basics of microbeads?
use beads coated with antigen and add serum - goes through light laser and given automated measure
what are the clinical characteristics of RA?
pain and stiffness in small joints of hand that is worse in morning and better when start to move over 1-2 hours. On an Xray can see per-articular swelling and effusion of MCP joints. There may be osteopenia, joint space narrowing and erosions
what will present in a blood test of RA?
high platelets and RF
what are rheumatoid factors?
antibody IgG, M or A against the Fc portion of IgG which is most common in RA. Autoantibody is CCP
why are RF not specific to RA?
they are seen in other diseases where there is polyclonal stimulation of B cells such as in chronic infection. The sensitivity and specificity of the test is around 70%
what are the autoantibodies in SLE?
Sm and dsDNA
what is anti-CCP AB used for?
it is a more specific test (95%) for RA than RF is. It has similar sensitivity to RF and is a useful prognostic marker. Those with a positive ACPA tend to have more severe and erosive disease
what are the characteristics of the self associated IgG RF?
there is a hypervariable combining site and galactose in the Fab portion and in the Fc portion a Fc epitope and a galactose pocket
what would you label and antihuman antibody with ?
peroxidase - colourless chromagen when it binds with a human AB against CCP will stain
how can vasculitis present?
RASH, fever, fatigue, muscle pain, high creatinine, haematuria, high urea, weight loss, night sweats, granulomatosis with polyangitis
how will an anti-neutrophil cytoplasm test with vasculitis present?
positive - ANCA (antineutrophilic cytoplasmic antibodies) is pattern and the pattern is PR3/MPO
how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (granulomatosis)?
granulomatosis with polyangitis
histology - leukocytoklastic vasculitis, necrotisin, granulomatous inflammation
ENT - nasal septum perforation, saddle nose deformiting, conductive or sensorineural hearing loss, subglottic stenosis
eyes - orbital pseudotumours, scleritis, episcleritis and uveitis
lung - nodules, infiltrates or cavitary lesions and alveolar haemorrhage
kidneys - segmental necrotising glomerulonephritis
heart - occassional valvular lesion
peripheral nerves - vasculitic neuropathy in 10%
eosinophilia - mild occassionally
how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (microscopic polyangitis)?
histology - no granulomatous inflammation, leukocytoklastic vasculities
ENT - absent or nild
eye - occassional eye disease - uveitis, episcleritis and scleritis
lung - alveolar haemorrhage
kidney - segmental necrotising glomerulonephritis
heart - rare
peripheral nerves - vasculitic neuropathy (60%)
no eosinophilia
how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (Cleurg-Strauss syndrome)?
histology - eosinophilic infiltrates and vasculitis and granulomas have eosinophilic necrosis
ENT - nasal polyps, conductive hearing loss and allergic rhinitis
eye - occasional eye disease
lung - asthma, fleeting infiltrates and alveolar haemorrhage
kidney - rare but segmental necrotising glomerulonephritis
heart - heart failure
peripheral nerves - vascular neuropathy in 80%
eosinophilia - all
what is cytoplasmic cANCA?
the granular fluorescence of the cytoplasm with nuclear sparing to the target antigens PR3 mostly and MPO
what is perinuclear pANCA?
the apparent fluorescence of the nucleus only targetting antigens MCO mostly and PR3
what is the clinical use of ANCA?
positive is useful in diagnosis but histopathology is still gold standard. the presence of ANCA with no symptoms does not indicate need for continued treatment and positive ANCA in patient in remission suggests flare up. Negative ANCA does not mean does not have disease
how would a IF screening of liver be done?
rodent tissue block and antigen specific ELISA
when is the liver screening done for AID?
when the liver tests are deranged in a non invasive way
what would anti-mitochondrial ABs show?
primary biliary sclerosis
what would anti-liver, kidney or microsomal, or anti smooth muscle ABs show?
autoimmune hepatitis
what autoantibodies can there be in diabetes type I?
islet cell antibodies, anti-GAD 65 and 67, anti-insulinoma antigens, insulin autoantibodies - these can reduce as disease progresses due to disappearance of the structures so attack drive reduces
why is it important to identify the antibody in a diabetic patient?
to identify the family members at risk
how would you test for addisons?
slice of adrenal on a side and see if patient has ABs
what is the basis of addisons?
autoantibodies targeting the adrenal cortex - impairs production of cortisol
what is the antigen in pernicious anaemia?
H+K+-ATPase located in the gastric parietal cells of the stomach - clinical AB is present in more than 90% of patients
how is pernicious anaemia characterised and what results in it?
it is characterised by antibodies to GPCs and intrinsic factor and autoimmune gastritis can lead to it
