IMMUNO: Autoimmune and autoinflammatory conditions Flashcards
Name 2 monogenic auto-inflammatory conditions.
FMF (AR)
TRAPS (AD)
What protein is involved in FMF vs TRAPS?
Pyrin-marenostrin expressed in neutrophils (FMF) TNF receptor (TRAPS)
What 2 cytokines are most involved in monogenic auto-inflammatory conditions?
IL-1 and TNF-alpha
What are 4 parts of body affectedi in FMF?
Abdo pain
Arthritis
Chest pain/pleurisy
Rash
What is a complication of FMF?
AA amyloid - liver produced
What are 3 tx for FMF?
Colchicine - anti-neutrophils
IL-1 blockade
TNF-alpha blockade
Name a monogenic autoimmune disease
APS-1/APECED
ALPS
IPEX
What is the defect in ALPS?
Abnormal lymphocyte apoptosis -FAS pathway mutation
What is the defect in IPEX?
Abnormal Tregs - FoxP3 mutation –> autoreactive B cells
How does IPEX manifest?
Diarrhoea, diabetes, dermatitis (also hypothyroidism)
How can ALPS present?
large spleen and large lymph nodes + lymphoma
What group does IBD, osteoarthritis and GCA/Takayasu’s fall into?
Polygenic autoinflammatory
What mutation is important in Crohn’s?
IBD1 gene on Chr16 with NOD2/CARD15
Apart from Crohn’s where is NOD2/CARD15 seen?
Blau syndrome and sarcoidosis
What does NOD2 mutation result in?
Autophagy in DCs
What are the tx mechanisms for Crohn’s?
Corticosteroids
Anti-TNF-alpha ab
Name 3 mixed pattern diseases.
Psoriatic arthritis
Behcet’s
Axial spondyloarthritis
What is the most important HLA in AS?
HLA-B27 –> presents antigen to CD8 T cells
What tx mechanisms are used for
NSAIDs
Anti-TNF-alpha
Anti-IL17
IL23R is also associated with AS, what is its function?
Th17 proliferation
What group does SLE, RhA and PBC fall into?
Polygenic autoimmune
Name 2 polymorphisms associated with T cell overactivation in polygenic autoimmune conditions.
PTPN22
CTLA4
What is HLADR3/4 linked to?
T1DM
What is HLADR4 and HLADr1 linked to?
RhA
What is HLADR15 linked to?
Goodpasture’s
What is HLADR3 linked to?
SLE and Grave’s
What is type II and type IV hypersensitivity?
II = Ab against cellular antigen –> cytotoxic or receptor activation (Graves - although sometimes considered type V)
IV= T-cell mediated –> delayed type
What type hypersensitivity is pemphigus vulgaris? What is the auto-antigen?
Type II, epidermal cadherin
Name 3 other type II autoimmune conditions.
MG
Graves
Goodpasture’s (–> glomerulonephritis + pulm haemorrhage) a.k.a. anti-GBM disease
Name a type III autoimmune condition.
SLE
Name a type IV autoimmune condition.
T1DM - CD8 T cell attack, antibodies pre-date development of any disease
Name 4 ANA related conditions.
SLE
Sjogren’s
Systemic sclerosis
Dermato/polymyositis
What is the goitre in Hashimoto’s infiltrated by?
B and T cells
Which Abs are related to damage to thymocytes in Hashimoto’s?
Anti-thyroid peroxidase
Name 4 autoantibodies in T1 diabetes.
Anti-insulin
Anti-islet cell
Anti-IA2
Anti-GAD
What IBD are pANCA associated with?
UC>Crohn’s
List 3 Abs associated with autoimmune hepatitis.
Anti-SMA
Anti-LKM
ANA
What Abs are associated with PBS?
Anti-mitochondrial
and pANCA?
What are these abs associated with?
- anti-strational
- anti-NMDA R
- anti AQP4
- anti-MOG
- MG with myositis
- encephalitis
- neuromyelitis optica spectrum disorder
- optic neuritis, encephalomyelitis
Which polymorphisms starting with ‘P’ are found in RhA?
PAD2, PAD4, PTPN22
What are PAD2/4 involved in?
Enzymatic conversion of arginine to citrulline which builds up in RhA –> anti-CCP
What increases citrullination in RhA?
Smoking
Porphyromonas gingivalis gum infection (expresses PAD)
What type of Ab is RF?
IgM anti-IgG
Name 4 things required to test for ANA.
Hep2 cells
Patient’s serum (with Abs)
Anti-human antibody with fluorescent tag
UV light
Name 3 antibodies against nuclear antigens and 2 antibodies against cytoplasmic antigens in SLE.
Nuclear = DNA, histones, snRNP Cytoplasmic = ribosomes, scRNP
Compare lupus (III) vs Goodpasture’s (II) renal disease.
Lupus = lumpy bumpy/granular deposition Goodpastures= linear deposition of Ig
What ANA titres are seen in SLE?
> 1:640 (normal 1:80)
Name a topoisomerase targeted by ANA.
SCL70
What is the ‘speckled’ ab appearance associated with?
Abs to nuclear antigens e.g. ribonucleoproteins
Name some ribonucleoproteins.
Ro, La, Sm, U1RNP (also called anti-ENA i.e. extractable nuclear antigen)
Are anti-ENA seen in SLE?
Not usually
Which complement is low in active disease vs severe?
Active - only C4 low
Severe - both low
Which syndrome is livedo reticularis associated with?
Antiphospholipid
What 3 abs are seen in antiphospholipid syndrome?
Anti-cardiolipin
Lupus anticoagulant
Anti-B2 glycoprotein 1
Where does CREST stop?
Does not go beyond forearms (although may involve peri-oral)
What systems does limited vs diffuse SS affect?
Limited = CREST Diffuse = CREST + pulm + renal + GI
Which abs are seen in limited vs diffuse SS?
Limited = anti-centromere Diffuse = Scl70, RNA polymerase, fibrillarin
What is dermatomyositis and polymyositis collectively known as?
Idiopathic inflammatory myopathy
In which IIM do CD8 T cells target myofibres via perforin/granzymes?
Polymyositis
In which IIM are perivascular CD4 and B cells seen with immune complex vasculitis?
Dermatomyositis
What abs are in the extended myositis panel?
Anti:
- amino-acyl transfer RNA synthase e.g. anti-Jo
- signal recognition peptide antibody
- Mi2
Is anti-Mi2 more common in dermato or polymyositis?
Dermatomyositis
How does anti-Jo stain?
Cytoplasmic
Where is anti-Sm ab seen?
SLE
Where is anti-RNP seen?
SLE and mixed connective tissue disease(like Sjogren’s etc)
Name a mixed vessel vasculitis.
Behcet’s
Name a medium vessel vasculitis.
Kawasaki and PAN
Which small vessel vasculitis is associated with cytoplasmic fluorescence? Which Ab?
Proteinase 3 - cANCA i.e. eGPA, MPA
Which small vessel vasculitis is associated with perinuclear fluorescence? Which Ab?
Myeloperoxidase - pANCA i.e. GPA
