diagnosis of autoimmune disease

Question 1

what should the immune system be?

Answer 1

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

Question 2

how do we detect when there is no self tolerance?

Answer 2

various laboratory tests will identify when there is autoantibodies in the patient’s blood directly against their own antigens and resulting in autoimmune conditions

Question 3

what is scleroderma?

Answer 3

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

Question 4

how would you diagnose scleroderma?

Answer 4

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

Question 5

what does SCL show?

Answer 5

diffuse systemic sclerosis

Question 6

what is the aim of diagnostic tests?

Answer 6

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

Question 7

what is sensitivity?

Answer 7

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

Question 8

what is specificity?

Answer 8

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

Question 9

what happens if you move the cut off of a test to the left?

Answer 9

reduces chance of false negative - loose sensitivity and vice versa

Question 10

what are non specific diagnosis tests?

Answer 10

inflammatory markers - ESR, CRP, ferritin, fibrinogen, haptoglobin, albumin and complement

Question 11

what are specific disease tests?

Answer 11

autoantibody testing and HLA typing

Question 12

what are ANA?

Answer 12

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

Question 13

what is the basic of detection of ANA?

Answer 13

primary reaction by adding serum to large cell, secondary reaction with labelled flurochrome, and then macroscopic examination through indirect immunofluorescence

Question 14

how can you detect different diseases in ANA detection?

Answer 14

different diseases have different patterns of binding

Question 15

what is the basics of an immunoblot?

Answer 15

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

Question 16

what is the basics of microbeads?

Answer 16

use beads coated with antigen and add serum - goes through light laser and given automated measure

Question 17

what are the clinical characteristics of RA?

Answer 17

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

Question 18

what will present in a blood test of RA?

Answer 18

high platelets and RF

Question 19

what are rheumatoid factors?

Answer 19

antibody IgG, M or A against the Fc portion of IgG which is most common in RA. Autoantibody is CCP

Question 20

why are RF not specific to RA?

Answer 20

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%

Question 21

what are the autoantibodies in SLE?

Answer 21

Sm and dsDNA

Question 22

what is anti-CCP AB used for?

Answer 22

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

Question 23

what are the characteristics of the self associated IgG RF?

Answer 23

there is a hypervariable combining site and galactose in the Fab portion and in the Fc portion a Fc epitope and a galactose pocket

Question 24

what would you label and antihuman antibody with ?

Answer 24

peroxidase - colourless chromagen when it binds with a human AB against CCP will stain

Question 25

how can vasculitis present?

Answer 25

RASH, fever, fatigue, muscle pain, high creatinine, haematuria, high urea, weight loss, night sweats, granulomatosis with polyangitis

Question 26

how will an anti-neutrophil cytoplasm test with vasculitis present?

Answer 26

positive - ANCA (antineutrophilic cytoplasmic antibodies) is pattern and the pattern is PR3/MPO

Question 27

how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (granulomatosis)?

Answer 27

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

Question 28

how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (microscopic polyangitis)?

Answer 28

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

Question 29

how will histology, ENT, eyes, lungs, kidney heart, peripheral nerves and eosinophilia present in the features of ANCA associated system vasuclitides (Cleurg-Strauss syndrome)?

Answer 29

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

Question 30

what is cytoplasmic cANCA?

Answer 30

the granular fluorescence of the cytoplasm with nuclear sparing to the target antigens PR3 mostly and MPO

Question 31

what is perinuclear pANCA?

Answer 31

the apparent fluorescence of the nucleus only targetting antigens MCO mostly and PR3

Question 32

what is the clinical use of ANCA?

Answer 32

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

Question 33

how would a IF screening of liver be done?

Answer 33

rodent tissue block and antigen specific ELISA

Question 34

when is the liver screening done for AID?

Answer 34

when the liver tests are deranged in a non invasive way

Question 35

what would anti-mitochondrial ABs show?

Answer 35

primary biliary sclerosis

Question 36

what would anti-liver, kidney or microsomal, or anti smooth muscle ABs show?

Answer 36

autoimmune hepatitis

Question 37

what autoantibodies can there be in diabetes type I?

Answer 37

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

Question 38

why is it important to identify the antibody in a diabetic patient?

Answer 38

to identify the family members at risk

Question 39

how would you test for addisons?

Answer 39

slice of adrenal on a side and see if patient has ABs

Question 40

what is the basis of addisons?

Answer 40

autoantibodies targeting the adrenal cortex - impairs production of cortisol

Question 41

what is the antigen in pernicious anaemia?

Answer 41

H+K+-ATPase located in the gastric parietal cells of the stomach - clinical AB is present in more than 90% of patients

Question 42

how is pernicious anaemia characterised and what results in it?

Answer 42

it is characterised by antibodies to GPCs and intrinsic factor and autoimmune gastritis can lead to it