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PATH FINAL > Immuno: Autoinflammatory and Autoimmune diseases 1 > Flashcards

Immuno: Autoinflammatory and Autoimmune diseases 1 Flashcards

1
Q

What is the difference between autoinflammatory and autoimmune disease?

A

Autoinflammatory = driven by components of the innate immune system

Not characterised by autoantibodies and HLA associations are usually less strong

Autoimmune = driven by components of the adaptive immune system

Autoantibodies are found and HLA associations are common

Note: mixed pattern diseases involve mutations affecting the innate and adaptive immune system → HLA associations may be present but autoantibodies are NOT usually a feature

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2
Q

Which cells are mainly responsible for:

  1. Autoinflammatory diseases
  2. Autoimmune diseases
A
  1. Autoinflammatory diseases = macrophages and neutrophils (disease is usually localised)
  2. Autoimmune diseases = T and B cells
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3
Q

List examples of monogenic autoinflammatory diseases

A

Familial Mediterranean Fever

TRAPS

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4
Q

List examples of polygenic autoinflammatory diseases

A

Crohn’s

UC

Osteoarthritis

Giant cell arteritis

Takayasu’s

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5
Q

List examples of monogenic autoimmune diseases

A

APECED

IPEX

ALPS

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6
Q

List examples of polygenic autoimmune diseases

A

Rheumatoid arthritis

Myasthenia

Pernicious anaemia

Graves disease

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7
Q

List examples of mixed pattern diseases

A

Ankylosing spondylitis

Psoriatic arthritis

Behcet’s

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8
Q

Mutations in which pathways are implicated in monogenic autoinflammatory disease?

A

Innate immune cell function - abnormal signalling via key cytokine pathways involving TNF-alpha or IL-1

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9
Q

Which gene mutation causes Familial Mediterranean Fever and which protein does this gene encode?

A

MEFV gene

Encodes pyrin-marenostrin which is ordinarily a negative regulator of the inflammatory pathway (predominantly IL1) → mutation leads to increased inflammation

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10
Q

What is the inheritance pattern of Familial Mediterranean Fever?

A

Autosomal recessive

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11
Q

Which cells contain pyrin-maronestrin?

A

Neutrophils

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12
Q

Outline the clinical presentation of Familial Mediterranean Fever.

A

Periodic fevers lasting 2-4 days associated with:

  • Abdominal pain (peritonitis)
  • Chest pain (pleurisy, pericarditis)
  • Arthritis
  • Rash
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13
Q

What is a complication of Familial Mediterranean Fever?

A

AA amyloidosis (due to chronic elevation of serum amyloid A which is an acute phase protein stimulated by the constant inflammatory action)

This can deposit in the kidneys causing nephrotic syndome and renal failure (predominantly renal failure)

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14
Q

Outline the treatment of Familial Mediterranean Fever.

A
  • Colchicine 500µg BD (binds to tubulin and disrupts neutrophil migration and chemokine secretion)
  • 2nd line: blocking cytokines
    • Anakinra - IL-1 receptor blocker
    • Etanercept - TNF-alpha blocker
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15
Q

What are three types of pathogenesis in monogenic autoimmune diseases?

A
  • Abnormality in central tolerance
  • Abnormality in regulatory T cells (peripheral tolerance)
  • Abnormality of lymphocyte apoptosis
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16
Q

What does APECED stand for?

A

Autoimmune polyendorcinopathy candidiasis ectodermal dystrophy

NOTE: it is autosomal recessive

17
Q

What mutation causes APECED? What is the role of this gene?

A

AIRE - this is a transcription factor that is responsible for the expression of self-antigens in the thymus and promotes apoptosis of self-reactive T cells. Defects in AIRE leads to a failure of central tolerance and the release of auto-reactive T cells.

18
Q

Which autoimmune conditions tend to occur in APECED?

A
  • Hypoparathyroidism (COMMON)
  • Addison’s disease (COMMON)
  • Hypothyroidism
  • Diabetes mellitus
  • Vitiligo
19
Q

Why are patients with APECED prone to Candida infection?

A

They produce antibodies against IL-17 and IL-22

20
Q

What does IPEX stand for?

A

Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome

21
Q

What mutation causes IPEX? What is the role of this gene?

A

FoxP3 - required for the development of Treg cells

A lack of Tregs leads to autoantibody formation

22
Q

Which autoimmune conditions are often seen in IPEX?

A
  • Diarrhoea (Enteropathy)
  • Diabetes mellitus
  • Dermatitis
  • Hypothyroidism

the 3 D’s

23
Q

What does ALPS stand for?

A

Autoimmune lymphoproliferative syndrome

24
Q

Which mutations cause ALPS?

A

Mutations in the FAS pathway leading to defects in apoptosis of lymphocytes

This leads to a failure of lymphocyte tolerance (as autoreactive lymphocytes don’t die by apoptosis) and failure of lymphocyte homeostasis (you keep producing lymphocytes)

25
Q

Describe the clinical phenotype of ALPS.

A
  • High lymphocyte count
  • Large spleen and lymph nodes
  • Autoimmune disease (usually cytopaenias)
  • Lymphoma
26
Q

What is the best known chromosomal region that is implicated in Crohn’s disease?

A

IBD1 on chromosome 16

27
Q

Which gene in this region is associated with Crohn’s disease?

A

NOD2 (aka CARD15)

Abnormalities are associated with increased risk of Crohn’s, Blau syndrome and some forms of sarcoidosis

28
Q

Where is NOD2 found and what is its role?

A

Cytoplasm of myeloid cells

Acts as a microbial sensor (recognises muramyl dipeptide)

29
Q

Outline the treatment approaches to Crohn’s disease

A
  • Corticosteroids
  • Azathioprine
  • Anti-TNF-alpha antibodies
  • Anti-IL 12/23 antibodies
30
Q

What is the strongest genetic association of ankylosing spondylitis?

A

HLA-B27

NOTE: others of note IL23R and ILR2

31
Q

Outline the roles of HLAB27, ILS23R and ILR2 in Ankylosing Spondylitis

A

HLA B27 = reason unknown - HLA-B27 known to be regarding presenting antigens to CD8 T cells

IL23R = receptor for IL23 which promotes Th17 action (adaptive immune)

ILR2 = inhibits IL1 activity (innate immune system)

32
Q

Where does ankylosing spondylitis tend to manifest?

A

At sites with high tensile forces (ligaments and tendon insertions)

33
Q

What are the treatment options for ankylosing spondylitis?

A
  • NSAIDs
  • Immunosuppression (anti-TNF-alpha and anti-IL17)

PATH FINAL (36 decks)

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