The Systemic Autoimmune Diseases Flashcards
Central Tolerance
testing B/T cells for self affinity
- autoreactive T-cells: killed
- autoreactive B-cells: modified
Function of AIRE protein
key protein in deleting autoreactive T-cells before birth
Peripheral Tolerance
rendering of autoreactive lymphocytes after birth
- self reactive lymphocytes rendered by CTLA-4/PD-1
- regulatory t-cells (CD25, IL-2, FOXP3) suppress self-immunity
- autoreactive T-cells undergo apoptosis when they activate
Most-often-mutated gene in autoimmunity
PTPN22
others – NOD2, IL-2, IL-7
Molecular mimicry
antigens on microbes mimic self-Ag
- immune response can cross-react to normal tissue
Microchimerism
increased number cells from mother in those with AI diseases
ANA: rim pattern
Systemic lupus
- anti ds-DNA
ANA: homogenous pattern
Drug-lupus
- anti-ssDNA, anti-histone
ANA: speckled pattern
think anything….
ANA: centromere pattern
CREST
ANA: nucleolar pattern
scleroderma
Anti-dsDNA
systemic lupus
- rim pattern on ANA
Anti-ssDNA
drug-induced lupus
Anti-histone
drug-induced lupus
Anti-Sm
systemic lupus (1/3 of patients with SLE)
Anti-Ro/SSA
Sjogren’s patients, neonatal lupus (heart block)
Anti-LA/SSB
Sjogren’s patients
Anti-U1RNP
mixed CT disease
Anti-Scl70
scleroderma
Anti-RNA polymerase III
scleroderma
Anti-centromere
CREST (mild scleroderma)
Anti-Jo
polymyositis/dermatomyositis
- severe disease, lung damage, arthritis
Anti-Mi2
dermatomyositis
Anti-SRP
severe polymyositis variant w/ severe necrotizing myopathy
Anti-P155/TIF1g and Anti-P140/MJ
juvenile and paraneoplasic dermatomyositis
Cardinal sign of SLE
butterfly rash
Systemic Lupus Erythematosus
antinuclear antibodies
- UV light triggers flareups
- females/kleinfelters more common
- Tissue injury from Type III, cell destruction from antibodies (Type II)
Models for SLE
- Drug reactions (hydralaine/procainamide/anti-aTNF, isoniazid)
- Genetic deficiences (C1q is used for removing apoptotic bodies)
How many criteria must a patient present with to be deemed SLE?
4/11 (now 4/17)
Hematoxylin bodies
stripped nuclei acted-on by ANA’s in lupus
- homogenized nuclei
LE cell
stripped nucleus opsonized by ANA
- devoured by phagocytes
What mediates lupus vasculitis?
immune-complex mediated
What is the appearance of the spleen in lupus?
adventitial onionskinning
What is an immune complex deposit in the glomerulus called?
wire loop
Lupus band test
granular Ig and complement at dermal-epidermal junction
What causes mouth ulcers in lupus?
infarcts from vasculitis
What are Libman-Sacks endocarditis?
In lupus, sterile thrombi on the lines of closure of valves
- can cause infarcts
Neonatal Lupus
develop rash, heart block (AV node) by mom’s auto-Ab (anti-Ro)
Blood in SLE
hypercoaguable
-polyclonal gammopathy (high Ig), lysis of RBC, destruction of neutrophils/platelets, low lymphocyte count, lupus anticoagulants, DVT (w/out lupus anticoagulants), thrombotic thyrombocytopenic purpura
Subacute cutaneous lupus
Anti-Ro is seen
- have rash with lupus (or sjorgren’s or RA)
Discoid lupus
rash with patches of scales and lost hairs
- hyperkeratosis as plugs (with hydropic changes)
- lymphocytes in patches
Drug-induced lupus
hydralazine, procainamide, isoniazid
- anti-histone Ab, and anti-dsDNA Ab (patients receiving anti-aTNF tx)
What glands does Sjogren’s effect primarily?
Salivary, lacrimal, pancreatic glands
- fill with lymphocytes
Symptoms of Sjorgren’s
autoimmunity against glands
- dry eyes and teeth decay (no healthy saliva)
- Mikulicz’s syndrome (enlarged glands)
- test for using schirmer test
- Potentially malignant lymphoma
Scleroderma
“systemic sclerosis”
- inflammation –> dense fibrosis (seen in hands that cannot flex/extend)
- abundant CD4+ T-cells, calcium deposits
- begins with Raynaud’s
- causes telangiectasias (vessels become dilated tufts)
- fibrosis of esophagus, small bowel, “onionskinning” of small renal artery
Raynaud’s
fingers begin to hurt and change color (red, blue, white)
- seen in cold
Common cause of death in Scleroderma
pulmonary fibrosis/pulmonary vascular narrowing
- pulmonary HTN
Why does scleroderma of small renal artery present a problem?
Kidney thinks pt is in shock –> releases renin –> increase blood pressure –> stroke/heart problems
Limited Scleroderma
not as rapid of onset/generalized distribution as systemic sclerosis
- CREST syndrome
CREST syndrome
- Limited scleroderma Calcinosis (deposits on skin) Raynaud's Esophageal fibrosis Sclerodactyly Telangiectasias
Morphea
Scleroderma-like changes in a patch
- CD4 rich –> fibrosis
Parry-Romberg
scar contracts over 1/2 of face and underlying skull is deformed
Eosinophilic fasciitis
tight skin with many eosinophils in subcutaneous and fascia
Polymyositis
CD8 lymphocytes into muscle (in the endomysium)
- sk. rather than sm. m
- high CK and aldolase
Dermatomyositis
CD4 T-cells, B-cells, plasma cells (within perimysium/around the blood vessels)
- MAC often seen in vessel wall
- muscle fibers at edges of fascicles are most likely atrophied
- Heliotrope rash (eyelashes turn purple)
- Gottron’s rash (reddish-purple) on knuckles (characteristic rash)
What is mechanic’s hands a sign of ?
Polymyositis/dermatomyositis/anti-synthetase (Jo1) syndrome
- dark keratin
Mixed Connective Tissue Disease (MCTD)
overlapping syndromes (lupus, scleroderma, RA, polymyositis)
- Anti-U1-RNP is high-titer Ab
- starts as synovitis of fingers plus Raynaud’s
- death is usually due to pulmonary vascular sclerosis/fibrosis (rash–> calcification)
IgG4-related disease
fibroinflammatory diseases
(Riedel’s fibrosing thyroiditis, AI pancreatitis, retroperitoneal fibrosis/periaortitis, fibrosis of salivary/lacrimal glands)
-features: fibrosis w/ cartwheel pattern, IgG4 lesions (high levels)
