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Muscluloskeletal Systems > Immunological Investigation of Multisystem Autoimmune Disease > Flashcards

Immunological Investigation of Multisystem Autoimmune Disease Flashcards

1
Q

Why are autoimmune diseases more common in women?

A

Oestrogen effects peripheral tolerance

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2
Q

What conditions are antinuclear antibody (ANA) associated with?

A 
SLE (>95%)
Drug-induced LE (95%)
MCTD (95%)
RA (50%)
Sjogren's (60%)
Scleroderma (60%)
Dermatomyositis (15%)
Old age (>40%)
Chronic inflammation (>30%)
Neoplasia (around 10%)
Chronic active hepatitis (70%)
PBC (25%)
Normaility (3-5%)
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3
Q

How useful is ANA in SLE and why?

sensitivity etc

A 
High sensitivity (95%)
Very Low specificity
  • High negative predictive value
  • Low positive predictive value

Good for ruling out ANA

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4
Q

4 different patterns of ANA staining are seen using flourescent test.

What are they?

A

Homogeneous:

Speckled Pattern Staining:

Nucleolar staining:

Peripheral/Membranous staining:

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5
Q

What is ANA Homogeneous pattern staining?

A

-Present where there are autoantibodies directed against chromosomal autoantigens
(double/single-stranded DNA or histone proteins)

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6
Q

What is ANA speckled pattern staining?

A

-Where there are autoantibodies directed against non-chromosomal nuclear proteins (which are physically distinct from the nucleic acids in the nucleus)

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7
Q

What is ANA nucleolar staining?

A

-Where autoantibodies are directed solely against nucleolar RNA

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8
Q

What is ANA Peripheral/Membranous staining?

A

-Where staining is confined to the nuclear membrane

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9
Q

How is the human nucleus effected by autoimmune disease?

A

The human nucleus contains numerous potential autoantigens (double-stranded DNA, single-stranded DNA, histone proteins, the nucleolus, and non-histone nuclear proteins). Autoantibodies are produced against different nuclear autoantigens in different connective tissue diseases. In some conditions, SLE particularly, autoantibodies can be produced against a range of nuclear autoantigens. This results in different staining patterns on testing when visualised down a microscope, the different patterns resulting from autoantibodies binding to autoantigens which vary in their physical distribution in the nucleus.

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10
Q

Homogeneous staining results from autoantibodies being directed against 1 or more of 3 nuclear autoantigens.

Name these autoantigens

Where do you see them?

A

Double stranded DNA
(dsDNA)
-SLE (60-90%)
-Some autoimmune liver disease

Single stranded DNA
(ssDNA)
-Non-specific
-Many inflammatory disorders

Histone proteins

  • drug induced lupus
  • other connective disorders
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11
Q

List the autoantigens which produce a speckled pattern of staining when relevant autoantidobies are present

A 
Ro
La
Sm
RNP
Scl-70
Jo-1
Centromere
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12
Q

Ro is present in which diseases?

A 
Sjogren's (60-70%)
SLE (30-40%)
SCLE
RA
Scleroderma
Neonatal lupus
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13
Q

Nucleolar pattern ANA’s are usually directed against what?

What diseases are these common in?

A

Nucleolus specific RNA

  • Scleroderma, systemic sclerosis and overlap syndromes (60-70%)
  • Clinical varients (limited cutaneous, diffuse cutaneous)
  • A range of variant-specific antibodies (e.g. fibrillarin, PM-Scl)
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14
Q

Peripheral/Membranous ANA

A

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15
Q

Peripheral/Membranous ANA staining is seen where autoantibodies are being produced against what?

What diseases is this seen in?

A

dsDNA

SLE
Some autoimmune liver diseases

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16
Q

What two patterns of staining are frequently seen as a combined staining pattern in patients with SLE?

A

Peripheral/ Membranous

Homogeneous

17
Q

How can ANA testing sub-classify disease like SLE?

Give examples

(dsDNA, Anti-Sm, RNP, Anti-Ro)

A

Patients who produce high levels of antibodies against dsDNA will tend to present with, or develop, renal complications and/or vasculitis.

Anti-Sm antibodies tend to be associated with renal and cerebral complications.

Antibodies against RNP are commonly associated with joint and muscle problems and with Raynaud’s phenomenon.

Anti-Ro is associated particularly with SLE with skin problems and symptoms of dry mouth/eyes due to autoimmune salivary/lacrimal gland destruction (secondary Sjogren’s syndrome).

18
Q

Small vasculitides can be split into 2 groups depending on what the conditions are associated with immunologically.

Name these two groups

A

ANCA-Associated Vasculitis

  • C-ANCA
  • P-ANCA

Immune Complex Associated Vasculitis

  • anti-GBM disease
  • HSP
  • SLE
  • Cryoglobulinaemia
  • Chronic infection
19
Q

What is the major autoantigen associated with C-ANCA and P-ANCA?

A 
C-ANCA = proteinase 3
P-ANCA = anti-MPO
20
Q

What disease is C-ANCA and anti-proteinase 3 associated with?

A

Granulomatosis with polyagitis

Wegener’s Disease

21
Q

What diseases is P-ANCA and anti-MPO associated with?

A

Microscopic polyangitis (70%)

Eosinophilic granulomatosis with polyangitis (about 50%
Churg-Strauss syndrome)

22
Q

What are 4 causes of secondary anti-phospholipid syndrome?

A

Connective tissue disorders
(SLE, RA, Systemic sclerosis, Sjogren’s)

Chronic infection
(HIV, Hep C, Malaria)

Drugs
(phenytoin, phenothiazines, anti-hypertensives)

Lymphoproliferative disease

23
Q

What are 4 major features of anti-phospholipid syndrome?

A

Vascular thrombosis (venous/arterial)

Recurrent fetal loss

Livedo reticularis

Thrombocytopenia

24
Q

Name 3 anti-phospholipid antibodies

A

Anticardiolipin antibodies

Anti-B2 glycoprotein I antibodies

“Lupus anticoagulant”

25
Q

The complement system is a component of the innate immune system and compromises what?

A

Collection of serum proteins organised into classical, alternate and terminal pathways

Control proteins in serum and body fluids which prevent inappropriate complement activation or downregulate and turn off complement activation

Series of cell surface control proteins which control and regulate the activity of the complement pathway

26
Q

What are the functions of the complement system?

A

Phagocyte chemotaxis

Opsonisation

Lysis of micro-organisms

Maintaining solubility of immune complexes

27
Q

The classical complement pathway is activated by what? Amongst other things

A

Immune complexes containing IgG and IgM

28
Q

The classical complement pathway is activated by what? Amongst other things

A

Immune complexes containing IgG and IgM

Antigen bound IgM is particularly effective at classical pathway activation

29
Q

What arec cryoglobulins?

A

Immunoglobulin molecules which reversibly precipitate out of solution at temperatures

30
Q

Describe the Brouet classification of cryoglobulins

Type, Components, prevalence, and what they are associated with

A

Type 1 (5-25%)

  • Monoclonal immunoglobulin
  • Plasma cell dyscrasias

Type 2 (40-60%)

  • Polyclonal IgG complexed with monoclonal IgM RF
  • Hep C, HIV

Type 3 (40-50%)

  • Polyclonal immunoglobulins
  • Connective tissue disease
31
Q

Cryoglobulins are associated with what clinical conditions?

A 
Livedo reticularis
Raynaud's
Peripheral cyanosis
Purpura/ Vasculitis
Glomerulonephritis
Neuropathy
Arthralgia
Thrombosis
Haemorrhage

Muscluloskeletal Systems (29 decks)

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