Core Immunology - Diagnosis of Autoimmune Diseases (10)

Question 1

Types of diagnostic tests

Answer 1

1. Non-specific - inflammatory markers

2. Specific - autoantibody test/HLA typing

Question 2

Non-specific inflammatory markers

Answer 2

1. ESR
2. CRP
3. Ferritin
4. Fibrinogen
5. Haptoglobin
6. Albumin
7. Complement

Question 3

ESR (erythrocyte sedimentation rate)

Answer 3

Blood in capillary tube, see how long takes to drop to bottom, viscosity increases during inflammation

Question 4

CRP (c-reactive protein)

Answer 4

Liver rapidly produces and uses in an inflammatory response, activates complement system, activated by IL-6 secretion

Question 5

Ferritin

Answer 5

Elevated

Question 6

Fibrinogen

Answer 6

Elevated

Question 7

Haptoglobin

Answer 7

Binds to Hb allowing it to be degraded, elevated

Question 8

Albumin

Answer 8

Lowered

Question 9

Complement

Answer 9

SLE antibody leads to increase immune complexes, C3 and C4 decrease

Question 10

Sensitivity

Answer 10

Measure of how good the test is in identifiying people with the disease

Question 11

Specificity

Answer 11

Measure of how good the test is at correctly defining people without the disease

Question 12

Positive predicitive value

Answer 12

The proportion of people with a positive test who have target disorder

Question 13

Negative predictive value

Answer 13

The proportion of people with a negative test who don’t have the target disorder

Question 14

ANA

Answer 14

Extractable nuclear antigens

Question 15

Detection of ANA

Answer 15

Detect if antibodies against nucleus, serum and fibroblast-like cells on slide, secondary antibody added, recognises IgG with fluorescent markers

Question 16

ANA present in

Answer 16

SLE, acute episode of illness (flu/infection), more in elderly

Question 17

Detection of Anti-dsDNA

Answer 17

Crithidia luciliae assay (protosoa), Farr assay, ELISA

Question 18

Detection of ENA’s

Answer 18

Immunoblots, individual ELISA’s, combination of antigens

Question 19

Detection of dsDNA and ENA’s

Answer 19

Used to work out specific target of ANA (>100 different antibodies described in SLE)

Question 20

ANA screen

Answer 20

dsDNA, Chromatin, ribosomal protein, SS-A, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, Centromere B

Question 21

Multiplex assessment non-organ specific autoantibodies with novel microbead-based immunoassay

Answer 21

20/30 beads with internal colouring, attach bead to antigen e.g. dsDNA, use a secondary antibody - which antigen and what bead, use laser

Question 22

Rheumatoid factor

Answer 22

Antibody (IgM, IgG, IgA) directed against Fc portion of IgG, found in RA (70%) and chronic infections (vasculitis)

Question 23

Anti-CCP (ACPA)

Answer 23

95% specific RA, more severe and erosive disease

Question 24

Cytoplasmic (c)ANCA

Answer 24

Granular fluorescence of neutrophil cytoplasm with nuclear sparing

Question 25

(c) ANCA target antigens

Answer 25

PR3, Azurocidin, Lysozyme, MPO

Question 26

Perinuclear (p)ANCA

Answer 26

Apparent fluorescence of the nucleus only

Question 27

(p) ANCA target antigens

Answer 27

MPO, Azurocidin, B-glucuronidase, Cathepsin G, PR3

Question 28

Clinical utility of ANCA testing

Answer 28

- Histopathology is gold standard for diagnosis - Neg ANCA doesn't exclude vasculitis (10-50% neg) - Correlation between return of ANCA and disease flare is poor - Persistence of ANCA and no clinical signs - dont need treatment

Question 29

Autoimmune liver disease

Answer 29

- Anti-mitochondrial Ab for primary biliary sclerosis | - Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs for autoimmune hepatitis

Question 30

How are autoimmune liver disease antibodies detected?

Answer 30

IF screening using rodent tissue block (oesophagus, liver and kidney) and antigen specific ELISA

Question 31

Autoantibodies in Type 1 DM

Answer 31

- Islet cell antibodies - Anti-GAD65/67 - Anti-insulinoma antigen 2 (IA-2) - Insulin autoantibodies (IAAs) - Disappear with progression of disease and total destruction of B islet cells

Question 32

Diagnosis and autoantibodies of Type 1 DM

Answer 32

Disease conformation, identify relatives and patients at risk