Autoantibodies

Question 1

How are autoantibodies produced?

Answer 1

Antigen-specific proteins are produced by B-lymphocytes in response to exposure to an antigen. Some cross-react with the body’s own constituents causing autoimmune disease.

Question 2

Define sensitivity and specificity of a test

Answer 2

Sensitivity is the % of people with the disease who receive a positive test.
Specificity is the % of people without the disease who are -ve

Question 3

What are the 2 best autoantibody tests to send off for the diagnosis of RA? which is more specific?

Answer 3

Anti-CCP (better) and RF

Question 4

What is the most specific auto-antibody for SLE
What levels should be monitored for disease activity

Answer 4

Anti-DsDNA
It is almost exclusive to SLE

C3C4 levels are used to monitor for disease activity (low=more active)

Question 5

Is ANA/anti-nuclear factor used to diagnose or monitor disease activity? or Both?

How are levels of ANA obtained and reported?

Answer 5

both

Levels expressed via “screening/serial dilutions” as a titre 1:X where the greater X is, the more likely they are to have significant rheumatological disease

Question 6

Which patient is more likely to have significant rheumatological disease?
Patient 1: Titre of ANA: 1:250
Patient 2: Titre of ANA: 1:25000

Answer 6

Patient 2: 1:25000 means that the sample needed to be diluted 25,000 times for ANA to becvome detectable

Question 7

A 25 year old female presents to her general practitioner with increasing lethargy and a facial rash which becomes more pronounced when she spends time in the sun. She also reports recent hair loss.

Blood tests reveal:
– Positive ANA, 1:320 (speckled)
– Positive dsDNA
– Rheumatoid factor RF 28 u/ml
(normal <20 u/ml)

What is the most likely diagnosis?

Answer 7

DsDNA is almost exclusively found in SLE => SLE

But remember that the presence of antibodies does not confirm the disease and its absence does not exclude it especially with the frequency of overlap between diseases => clinical findings must support diagnosis

This patient most likely has SLE – this is suggested clinically by the presence of constitutional symptoms – fatigue/lethargy, and by the photosensitive skin lesions, in this case a malar rash, in addition to alopecia
– this is most likely to be patchy/frontal/peripheral in SLE

Question 8

This finding is most consistent with…

Answer 8

Butterfly rash seen in SLE. Worse when exposed to sunlight

Question 9

A 47 year old female presents to her general practitioner with increasing breathlessness on exertion. She has noted tightening of her skin on her face and hands. She also complains of painful colour
change when her hands are exposed to the cold.

Blood results reveal:
*Positive ANA 1:640, nucleolar pattern
*Positive ENA :SCL-70

What is the most likely diagnosis?

Answer 9

This patient’s presentation includes a number of key
clinical features (CREST)
-Raynaud’s phenomenon (exaggerated vascular
response to cold)
-Dyspnoea on exertion suggests pulmonary
involvement – extra-articular (systemic) features
-Tightening or thickening of skin (sclerosis)
-The positive ANA with significant titre suggests the
presence of underlying autoimmune disease, with
the nucleolar pattern specific for scleroderma
-Positive ENA – SCL70 is common in patients with
diffuse scleroderma/systemic sclerosis

Question 10

This clinical finding is most consistent with…

Answer 10

Raynaud;s phenomenon consistent with scleroderma

Question 11

A 46 year-old man with a past medical history of Raynaud’s syndrome attends his doctor complaining of swollen hands with skin tightening and small ulcers on the fingertips, as well as aches in several joints. He has found it difficult to climb the stairs and to rise
from his chair. Blood tests reveal:
– Positive ANA (1:640)
– Positive anti-CCP
– Positive anti-RNP

What is the most likely diagnosis

Answer 11

Answer: Mixed connective tissue disease
–Polyarthralgia, scleroderma (swelling, thickening of hands)
–Raynaud’s syndrome
–Combination of different symptoms, i.e. “mixed” with positive anti-RNP
–Can have anti-CCP positivity with MCTD

This is why you need to combine clinical picture with the serology results

Question 12

The antigens most associated with SLE are…

Answer 12

Anti-DsDNA
Anti-smith
Anti-sm

Question 13

The antigens most associated with Sjogren’s syndrome are…

Answer 13

Anti-Ro
Anti-La

Question 14

The antigens most associated with Scleroderma/Systemic sclerosis are…

Answer 14

Anti-Scl70

Question 15

The antigens most associated with Polymyositis are…

Answer 15

Anti-Jo1

Question 16

The antigens most associated with Mixed Connective Tissue Disease are…

Answer 16

Anti-RNP

Question 17

A patient presents complaining of consistent gingival bleeds and easy bruising. Her past medical history includes a DVT as well as 2 recurrent miscarriages, one of which due to placental abruption.

What is the most likely diagnosis?
How will you confirm the diagnosis?

Answer 17

Antiphospholipid syndrome
=> Autoantibodies
Anticardiolipin
Lupus anti-coagulant
B2 Glycoprotein

Note that this might occur in isolation or in a/w SLE

Question 18

What is the most important antibody with regards to vasculitis? What are the different types?

Answer 18

ANCA - Anti-neutrophil cytoplasmic antibodies
C-ANCA
P-ANCA
A-ANCA

Question 19

What diseases are most associated with the following autoantibodies
C-ANCA
P-ANCA

Answer 19

C-ANCA: Granulomatosis with polyangitis
P-ANCA: Wegner’s Eosinophilic Granulomatosis with Polyangitis,, Microscopic polyangitis, and Renal-limited Vasculitis

Question 20

What is the main antibody used in the diagnosis of Good-pasture’s syndrome

Answer 20

Anti-GBM

ANCA may be positive in 10-40% of cases

Question 21

What autoantibodies are used in the diagnosis of Hashimoto’s thyroiditis?

Answer 21

Anti-TPO
Anti-Thyroglobulin

40% may be ANCA +ve

Question 22

What autoantibodies are used in the diagnosis of Grave’s Disease?

Answer 22

Anti-TSH receptor
Anti-TPO
Anti-Thyroglobulin

40% may be ANCA +ve

Question 23

What autoantibody may be positive in DM Type 1A?

Answer 23

Islet cell antibodies

Question 24

What is the significance of Islet cell antibodies

Answer 24

This is used to differentiate between Type1A from other forms such as MODY

Question 25

A 34 year-old woman attends your practice with a 6 week history of tremulousness, heat intolerance, hair thinning and loose stools. She has no past medical history and is on no medication. Physical exam displays hyperreflexia and a fine resting tremor, with no nodules palpable in the neck. Blood tests reveal:
– Free T4 35 pmol/L (9 – 22)
– TSH <0.5 m units/L (0.5 – 5.5)
– Positive TSH receptor antibody

What is the most likely diagnosis?

What other autoantibodies may be positive?

Answer 25

Grave’s disease

Anti-TPO
Anti-Thyroglobulin

Question 26

A 33 year old female with a past medical history of Grave’s disease attends her doctor with bloating, weight loss, foul smelling floating stools and increasing fatigue.
Haemoglobin is 10.4 g/dL (12-15 g/dL)

What initial diagnostic investigations should be carried out?
A. Tissue transglutaminase antibodies (tTG)
B. Islet cell antibodies
C. Anti-TSH receptor antibodies
D. Anti-cardiolipin antibodies
E. Anti-SCL 70 antibodies

What autoantibodies not mentioned above may also be positive in this case? (not Grave’s)

Answer 26

A - Anti-tTg antibodies (Tissue transglutaminase antibodies)

Why?
– Symptoms consistent with coeliac disease
– Pre-existing auto-immune disease (Grave’s)

Also Anti-IgA antibodies

Question 27

A 40 year-old female presents to her general practitioner with fatigue and severe itchiness on her limbs. She has no past medical history. Physical
examination reveals scratch marks and hepatomegaly. Blood tests reveal a mildly raised ALT and AST, markedly elevated alkaline phosphatase, normal bilirubin and positive anti-mitochondrial antibodies.

What is the most likely diagnosis?
A.Primary sclerosing cholangitis
B.Primary biliary cholangitis
C.Coeliac disease
D.Autoimmune hepatitis
E.Pernicious anaemia

Answer 27

B - Primary Biliary Colangitis

*Pruritis is common in PBC. (May precede the development of jaundice in
PBC). The associated fatigue is supportive of the diagnosis. Hepatomegaly is
often found in PBC.
*Alk P is almost always elevated. Aminotransferases may be normal or slightly
elevated. Bilirubin is often normal – poor prognostic sign when elevated.
*Elevated AMA would confirm this diagnosis – elevated in 95% of patients

Question 28

A 25 year old woman presents to general practitioner with ongoing fatigue and
small joint arthralgia. She puts this down to her demanding work as a receptionist.
On examination she has a well demarcated maculopapular erythematous rash on
both cheeks and the bridge of the nose. She reports that the rash is usually made
worse by the sunlight.

Which of the following may be seen during acute flare ups?
A. low complement levels (c3 and c4)
B. low C-reactive protein
C. low erythrocyte sedimentation rate
D. low IgG dsDNA levels
E. low serum caeruloplasmin

Answer 28

A - low complement levels (c3 and c4)

Question 29

A 25 year old man presents to Emergency Department with ongoing fatigue and back pain usually worse at night, which eases during the day. Vital signs reveal blood pressure of 120/75mmHg, temperature of 35 degrees Celsius, heart rate of 80 bpm and saturation of 97% on room air. On examination he has anterior uveitis and lower back examination is positive for reduced lateral
and forward flexion.

What serological abnormality is most likely to be
positive?
A. Anti-nuclear antibody
B. Anti-smooth muscle antibodies
C. C-ANCA
D. dsDNA
E. HLA B27

Answer 29

E - HLA B27

Question 30

A 39 year old woman presents to the GP with painful discoloration of both her hands. On examination, there is skin tightening from fingers to shoulders and in her face. She also complains of dysphagia.

Which of the following antibodies is most likely to have been positive?

A. Anti- SCL
B. Anti dsDNA
C. Anti-Smith
D. Anti-histone
E. Anti-RNP

Answer 30

A - Anti-SCL