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Pathology - Y5 > Autoimmune and Autoinflammatory Disease 3 > Flashcards

Autoimmune and Autoinflammatory Disease 3 Flashcards

1
Q

What are anti-nuclear antibodies?

A

Group of antibodies that bind to nuclear proteins.

Test by staining of Hep-2 cells (human epidermoid cancer line).

Very common.

Low titre antibodies (<1:80) often found in normal individuals (esp older women).

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2
Q

Which genetic abnormalities can predispose to SLE?

A

Abnormalities in clearance of apoptotic cells: Polymyorphisms in genes encoding complement, MBL, CRP.

Abnormalities in cellular activation: Polymorphisms in genes encoding/controlling expression of cytokines, chemokines, co-stimulatory molecules, intracellular signalling molecules. Results in B cell hyperactivity and loss of tolerance.

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3
Q

What do antibodies directed particularly at intracellular proteins result in?

A

Debris from apoptotic cells that have not been cleared

Nuclear antigens - DNA, histones, snRNP

Cytoplasmic antigens - Ribosome, scRNP

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4
Q

What is the pathophysiology of SLE?

A

Antibodies bind to antigen to form immune complexes.

Immune complexes deposit in tissues: Skin, joints, kidney.

Immune complexes activate complement (classical pathway).

Immune complexes stimulate cells expressing Fc and complement receptors.

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5
Q

What is the difference between immune complex (Type III) versus antibody mediated (Type II) disease pathology?

A

Immune complexes deposit in basement membrane in a type III response.

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6
Q

How can antibody levels be quantified?

A

Measured by titre (the minimal dilution at which the antibody can be detected) or by concentration in standardised units.

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7
Q

What are the targets of an anti-nuclear antibody?

A

dsDNA

Ro, La, Sm, U1RNP: Ribonucleoproteins

SCL70: Topoisomerase

Centromere

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8
Q

How is ANA investigated?

A

Homogeneous staining associated with specificity for dsDNA.

Specificity investigated with ELISA based assay.

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9
Q

What are anti-dsDNA antibodies?

A

Measures antibodies against double stranded DNA:

  • Are highly specific for SLE (95%)
  • Occur in ~60-70% of SLE patients at some time in their disease
  • Very high titres are often associated with more severe disease, including renal or central nervous system involvement.
  • Useful in disease monitoring

Can increase in antibody titre is associated with disease activity and may precede disease relapse. False positive results unusual (<3%).

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10
Q

What are speckled antibodies?

A

Associated with antibodies to extractable nuclear antigens.

Specificity is for some ribonucleoproteins (Ro, La, Sm, U1RNP) – confirm with ELISA.

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11
Q

What are anti-ENA antibodies?

A

Ro, La, Sm, RNP (all are ribonucleoproteins):

  • Antibodies may occur in SLE
  • Anti-Ro and La are also characteristically found in Sjogren’s syndrome
  • Titres not helpful in monitoring disease activity
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12
Q

What is the classical pathway of compliment activation?

A

Formation of antibody-antigen immune complexes:

  • Activate complement cascade via classical pathway.
  • Complement components become depleted if constantly consumed.

Quantitation of C3 and C4 acts as a surrogate marker of disease activity.

[NB we measure UNACTIVATED complement proteins, not activated forms]

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13
Q

What is the complement profile in inactive SLE?

A

C3: Normal

C4: Normal

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14
Q

What is the complement profile in active SLE?

A

C3: Normal

C4: Decreased

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15
Q

What is the complement profile in severe active SLE?

A

C3: Decreased

C4: Decreased

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16
Q

Which antibodies are present in anti-phospholipid syndrome?

A

Anti-phospholipid antibodies

  • Recurrent venous or arterial thrombosis
  • Recurrent miscarriage
  • May be associated with livedo reticularis, cardiac valve disease
  • May occur alone (primary) or in conjunction with autoimmune disease (secondary)
17
Q

What are three antibody tests for anti-phospholipid syndrome?

A

Lupus anti-coagulant

  • Prolongation of phospholipid-dependent coagulation tests
  • Cannot be assessed if the patient is on anticoagulant therapy

Anti-cardiolipin antibody

  • Antibody specific for negatively charged phospholipids

Anti-B2 glycoprotein 1 antibody

  • Antibody specific for glycoprotein found associated with negatively charged phospholipids

Check all three antibodies in individuals presenting with unexplained thrombosis or recurrent pregnancy loss

18
Q

What is Limited Cutaneous Systemic Sclerosis (CREST)?

A

Skin involvement does not progress beyond forearms (although it may involve peri-oral skin).

  • Calcinosis
  • Raynauds
  • Oesophageal dysmotility
  • Sclerodactyly
  • Telangectasia

Primary pulmonary hypertension.

19
Q

What is Diffuse Cutaneous Systemic Sclerosis?

A

Skin involvement does progress beyond forearms.

CREST features

  • More extensive gastrointestinal disease
  • Interstitial pulmonary disease
  • Scleroderma kidney/renal crisis
20
Q

Which antibodies are associated with limited cutaenous systemic sclerosis?

A

Anti-centromere antibodies

21
Q

Which antibodies are associated with diffuse cutaneous systemic sclerosis?

A

Nucleolar pattern

Anti-topoisomerase antibodies (Scl70)

RNA polymerase

Fibrillarin

22
Q

What is the pathophysiology of dermomyositis?

A

Within muscle – perivascular CD4 T cells and B cells.

Immune complex mediated vasculitis.

23
Q

What is the pathophysiology of polymyositis?

A

Within muscle – CD8 T cells surround HLA Class I expressing myofibres.

CD8 T cells kill myofibres via perforin/granzymes.

24
Q

What are appropriate investigations for myositis?

A

Positive ANA (in some patients): Extended myositis panel

Anti-aminoacyl transfer RNA synthetase antibody eg Jo-1 (cytoplasmic)

Anti-signal recognition peptide antibody (nuclear and cytoplasmic) (PM)

Anti-Mi2 (nuclear) (DM>PM)

25
Q

Which diseases are dsDNA +ve?

A

SLE

26
Q

Which diseases are ENA+ve?

A

Ro, La, Sm, RNP: SLE (any), Sjogrens (Ro, La)

SCL70: Diffuse cutaneous systemic sclerosis

Centromere: Limited cutaneous systemic sclerosis (CREST)

27
Q

Which diseases are cytoplasmic?

A

t-RNA synthetase (Jo1): Myositis

28
Q

Which diseases are associated with the following autoantibodies?

a) Anti-CCP Anti-cyclic citrullinated protein antibody

b) RF Rheumatoid factor (anti-IgG Fc antibody)

c) ANA Anti-nuclear antibody

d) Anti-dsDNA

e) Anti-Sm

f) Anti-RNP

g) Anti-Ro, anti-La

h) Anti-centromere

i) Anti-SCL70

j) Anti-Jo-1 (anti-histidyl tRNA synthetase) and other anti-tRNA synthetase antibodies

k) Anti-cardiolipin, anti-B2GPI, lupus anticoagulant

A

a) Rheumatoid arthritis

b) Rheumatoid arthritis, Primary Sjogrens

c) Connective tissue disease (screening)

d) Systemic lupus erythematosus

e) Systemic lupus erythematosus

f) Systemic lupus erythematosus or mixed connective tissue disease

g) Primary Sjogren’s or SLE

h) Limited cutaneous systemic sclerosis

i) Diffuse cutaneous systemic sclerosis

j) Idiopathic inflammatory myositis

k) Anti-phospholipid syndrome

29
Q

What are large vessel systemic vasculitis?

A

Takayasu’s arteritis

Giant cell arteritis/polymyalgia rheumatica

30
Q

What are medium vessel systemic vasculitis?

A

Polyarteritis nodosa

Kawasaki disease

31
Q

What are small vessel (ANCA associated) systemic vasculitis?

A

Microscopic polyangiitis

Granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis

32
Q

What are small vessel (immune complex) systemic vasculitis?

A

Anti-GBM disease

IgA disease

Cryoglobulinaemia

33
Q

What is a mixed vessel systemic vasculitis?

A

Behcet’s

34
Q

What is c-ANCA?

A

Cytoplasmic fluorescence

Associated with antibodies to enzyme proteinase 3

Occurs in > 90% of patients with granulomatous polyangiitis with renal involvement

35
Q

What is p-ANCA?

A

Perinuclear staining pattern.

Associated with antibodies to myeloperoxidase.

Less sensitive and specific than cANCA.

Associated with microscopic polyangiitis and eosinophilic granulomatous polyangiitis.

36
Q

Investigations show:

  • Positive antinuclear antibodies (ANA)
  • Anti-dsDNA+ve
  • Low C3 and C4
  • High ESR

Negative results for:

  • Ro, La, Sm, RNP
  • SCL70
  • Centromere
  • Jo-1
  • Anti-neutrophil cytoplasmic antibodies (ANCA)

What is the diagnosis?

A

Systemic lupus erythematosus

37
Q

Investigations show:

Positive anti-neutrophil cytoplasmic antibodies (ANCA)

Negative results for:

  • Anti-nuclear antibody (ANA)
  • Normal complement
  • Raised ESR and CRP

What is the diagnosis?

A

ANCA associated vasculitis

Pathology - Y5 (59 decks)

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