Autoinflammatory Flashcards
NLRP3 Gainer mutation
Muckle Wells syndrome
Familial cold auto-inflammatory syndrome
Chronic infantile cutaneous articular syndrome
All autosomal dominant - gainer mutation
All encode crypopyrin (stimulates ASC –> procaspase 1 –> IL-1, NfkB)
MEFV gene mutation
Familial Mediterranean Fever
MEFV encodes Pyrin-Marenostrin which is a negative regulator of ASC
Autosomal recessive
Loss of Pyrin-Marenostrin leads to increased activation of ASC by cryopyrin –> inflammation in neutrophils
Epidemiology
Sephardic>Ashkenazy Jews
Armenian, Turkish and Arabic people
MK mutation
Hyper IgD with periodic fever
MK= Mevanolate kinase
Autosomal recessive
TNFRSF1
TNF-associated periodic syndrome
TNF receptor mutation
Autosomal dominant
Muckle wells syndrome
Gainer mutation of NLRP3
Encodes NALP3 and Cryopyrin
Autosomal dominant
Leads to increase activity of Cryopyrin which activated ASC and procaspase 1 –> IL-1 and NFkB
Familial cold auto-inflammatory syndrome
Gainer mutation of NLRP3
Encodes NALP3 and Cryopyrin
Autosomal dominant
Leads to increase activity of Cryopyrin which activated ASC and procaspase 1 –> IL-1 and NFkB
Chronic infantile neurological cutaneous articular syndrome
Gainer mutation of NLRP3
Encodes NALP3 and Cryopyrin
Autosomal dominant
Leads to increase activity of Cryopyrin which activated ASC and procaspase 1 –> IL-1 and NFkB
Familial Mediterranean Fever
MEFV mutation
Clinical presentation
Periodic fevers lasting 48-96 hours associated with:
Abdominal pain due to peritonitis
Chest pain due to pleurisy and pericarditis
Arthritis
Long term risk of amyloidosis
Nephrotic syndrome
Renal failure
Treatment
Colchicine 500ug bd - binds to tubulin in neutrophils and disrupts neutrophil functions including migration and chemokine secretion
Anakinra (Interleukin 1 receptor antagonist)
Etanercept (TNF alpha inhibitor)
Type 1 interferon
Auto-immune polyendocrine syndrome type 1 (APS1)
Auto-immune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome / APECED
AIRE: Defect in ‘auto-immune regulator’
Transcription factor involved in development of T cell tolerance in the thymus
Upregulates expression of self-antigens by thymic cells
Promotes T cell apoptosis
Antibodies vs parathyroid and adrenal glands Hypoparathyroidism and Addison’s
Antibodies vs IL17 and IL22
Candidiasis
Autosomal recessive disorder
Addison’s
Hypoparathyroidism
Candidiasis
Auto-immune polyendocrine syndrome 1
APECED
Autosomal recessive disorder
AIRE Defect in ‘auto-immune regulator
Upregulates self-protein on thymic cells –> promoted T cell apoptosis
Anti-paraythroid and anti-adrenal gland
Anti-IL=17/IL-22 –> candidiasis
Mutations in Foxp3
IPEX
Immune dysregulation, polyendocrinopathy, enteropathy, X- linked syndrome
Overwhelming disease leads to early death without treatment
Endocrinopathy
Usually Insulin dependent diabetes mellitus, Thyroid disease
Diarrhoea
Eczematous dermatitis
Mutations in TNFRSF6 which encodes FAS
Auto-immune lymphoproliferative syndrome
ALPS
Mutations within FAS pathway
Defect in apoptosis of lymphocytes
Failure of tolerance
Failure of lymphocyte ‘homeostasis’
Auto-immune disease
Commonly auto-immune cytopenias (can be pancytopenias)
High lymphocyte numbers with large spleen and lymph nodes
May be associated with lymphoma
IBD 1-10
Crohn’s
IBD1
Chromosome 16 identified as NOD2 (CARD-15, caspase activating recruitment domain -15).
Failure to control bacteria adequately means bacteria can go on to trigger other inflammatory pathways increased inflammation
HLA-B27
IL-23 R
Ankylosing spondylitis
