Autoimmune and auto-inflammatory disease Flashcards
Familial Mediterranean Fever
Autoinflammatory monogenic disease
Loss-of-function mutation in MEFV1, which encodes pyrin-marenostrin
Inflammasome complex is not negatively regulated
There is intermittent fever lasting 2-3 days, with pleurisy, peritonitis, pericarditis, rash and arthritis
Risk of AA amyloidosis and kidney damage, as liver chucks out serum amyloid A
Tx with colchicine (2nd line is akinra or etanercept)
Akinra = IL-1R antagonist Etanercept= TNFa inhibitor
TRAPS
Autoinflammatory monogenic disease
TNFa Receptor Associated Periodic Syndrome
Mutations in TNFRSF1 which encodes TNFa receptor
Results in periodic fevers lasting > 1 week
Intense muscle pain, rash, peritonitis, pleurisy
Hyper IgD Periodic Syndrome
Autoinflammatory monogenic disease
Mutation in MK which encodes mevalonate kinase
Results in febrile attacks every 1-2 months
Intense inflammatory reaction - lymphadenopathy, hepatosplenomegaly, abdo signs, cutaenous signs
Raised IgD with low Mevalonate kinase
APECED
Autoimmune PolyEndocrine Candidiasis Ectodermal Dystrophy
Autoimmune monogenic disease
- Failure of T-cell tolerance due to defective AIRE
- Self-T-cells survive, and help B-cells so this is a MIXED autoimmune disease
IPEX
Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked
Autoimmune monogenic disease
- Mutation in Foxp3
- Don\t get negative regulation of T-cell response
DIARRHOEA, DIABETES AND DERMATITIS
(+ hypothyroidism!
ALPS
Autoimmune Lymphoproliferative Syndrome
Autoimmune monogenic disease
Mutation in Fas pathway, so lymphocytes cannot udnergo apoptosis
- Failure of central tolerance
- Splenomegaly
- Lymphadenopathy
- Lymphoma
Crohn’s Disease
Polygenic autoinflammatory disease
- NOD2/CARD15
Ankylosing spondylitis
MIXED PATTERN DISEASE
- HLA-B27
= Tx with NSAIDs, anti-TNFa and anti-IL17
Associations with T1DM?
HLA-DR 3
HLA-DR 4
Associations with Rheumatoid arthritis?
HLA-DR4
HLA-DR1
Associations with Graves disease?
HLA-DR3
Associations with Goodpasture’s disease?
HLA-DR15
PTPN22 polymorphism
Seen in SLE, T1DM, Rheumatoid arthritis
CTLA4 polymorphism
- Seen in SLE, T1DM and thyroid disease
Graves disease
- Type 2 Hypersensitivity reaction
- IgG binds to TSH receptors
- DR3!
hashimoto’s Thyroiditis
- Type 2 Hypersensitivity reaction
- IgG binds to TPO
Also TYPE 4 Hypersensitivity
- T-cel and B-cell infiltration
Myasthenia Gravis
- Type 2 Hypersensitivity reaction
- Antibodies bind to AchR
Goodpastures Disease
Type 2 HS
- antibodies bind to glomerular basement membrane
Type 1 Hypersensitivity
Soluble antigen (IgE)
- Immediate reaction
- IgE binds to a soluble antigen and causes mast cell degranulation and histamine release
- Vascular permeability, leukocyte chemotaxis and smooth muscle contraction
Examples
- Infantile dermatitis
- Food allergies
- Oral allergy syndrome
- Allergic rhinitis (blue mucosa)
Type 2 Hypersensitivity
Response to cellular antigen
IgM/IgA
- IgM or IgA binding to cellular antigen results in cytotoxicity or can sometimes just bind with no damage e.g. Graves disease
Examples
- HDN
- ITP
- Goodpasture’s
- Myasthenia Gravis
- MPA, GPA and eGPA
Type 3 hypersensitivity
Immune COMPLEX mediated damage
- SLE
- Polyarteritis nodosa
Type 4 hypersensitivity reaction
T-cell mediated
- T1DM
- MS
- Rheumatoid arthritis
- Contact dermatitis
- Crohn’s disease
Sjrogen’s syndrome
sjROgen’s syndrome
- anti-RO
- anti-La
Coeliac disease
DQ2
DQ8
