22. Lupus (SLE) Flashcards
SLE: wtf is it?
likely a collection of symptoms, all produced by autoimmune disturbances. not all appear in every patient.
Hallmark = production of autoantibodies
Immune complexes form & are deposited in organs
From notes: The serologic hallmark of SLE is the production of high titered autoantibodies directed against a wide variety of nuclear and other cellular components
SLE: what is age of onset?
F:M ratio?
bonus for ethnicities….
Usually presents at age 20-30
F:M = 8:1
more common in blacks, hispanics, polynesians, & more common in cities
Genetic predisposition?
has a gene been identified?
no obvious hereditary predisposition.
some increase in 1st degree relatives, some twin concordance
Gene ID: it is a multi-gene disease (at least 7 involved). One allele will not yield SLE.
CLinical presentation of SLE?
what are the 3 types?
what organ systems are involved?
No typical clinical presentation (every patient has their own brand!)
3 types: acute/fulminant; slowly progressive; flares/remissions (most common)
any organ system can be involved, often one is predominant.
what are the non-specific disease manifestations seen in over 80% of SLE patients?
-fatigue
-fever
-musculoskeletal disease (may mimic Rheumatoid Arth pattern- but no erosions. morning stiffness, muscle pain.)
what are a few clinical manifestations seen in over 50% of SLE patients (but not as freqently as fever/fatigue/musculoskel sx)?
SKIN: malar rash: 50%; photosensitivity: 50%; alopecia: 50%
(also renal, pulm, cardiac, CNS findings)
The diagnostic criteria he gave are used more for research classification than clnical use, but still helpful. There are 11 categories of SLE findings, of which a patient must have 4 to meet diagnosis. Name a few of these categories?
Malar rash
Discoid rash
photosensitivity
Oral ulcers
arthritis
serositis
renal disorder
neuro disorders
hematologic disorder
immunologic disorder
antinuclear antibodies
what is the most likely mechanism for how autoantibodies are made in SLE?
Antigens that were previously recognized as self are now recognized as non-self. The B cells are fine (they are not pathologic) but are attacking self.
Review: what are the molecules involved in B cell stimulation of CD4+ T cells?
see pic: note CD40/CD40L and B7/CD28 interactions between B cells and CD4+ Tcell
after this interaction, the T cell is activated and will proliferate.
The B cell is activated and will produce autoantibodies.
what is one way we have figured out how to slow autoimmune reactions in mice? does this work in people?
See “X” below… eliminate CD4+ T cells by treating with Anti-CD4+ antibody. –Stops activation of B cells –> less autoantibody production.
Another method: block the CD40-CD40L interactions.
In humans, the latter caused blood clots.
Once you have these circulating autoantibodies, how do they cause disease?
two ways:
- bind cells directly. leads to cell destruction (ex. hemolytic anemia) and cell dysfunction (ex. neuro dysfxn)
- cause circulating immune complexes, which deposit and initiate local immune response, leading to organ injury and dysfxn (“innocent bystander” effect)
not only do lupus patients make excessive amounts of immune complexes – what other issue concerning immune complexes do they have?
they have trouble clearing immune complexes from their circulation
(recall we normally do this via the reticulo-endothelial (RET) system in liver and spleen)
where in the skin layers do immune complexes tend to get stuck? how can we use this to diagnose lupus?
What is the test called?
immune complexes tend to get stuck at dermal-epidermal junction.
we can bind the complexes with fluorescent dye (FITC) and do immunofluorescence staining of skin biopsy. Will see deposits of Ig and C at the dermal-epidermal junction
Test = Lupus Band Test
3 rashes seen in lupus?
- malar rash (spares nasolabial folds)
- discoid rash (scalp involvement, some hypopigmentation)
- photosensitive rash
(Pic is photosensitive, not malar. remember malar spares the nasolabial folds)
List some vascular complications of lupus (4)?
- Raynaud’s
- Nailfold capillary involvement
- Vasculitis (organ ischemia, digital infarct)
- Retinal vasculitis
what is the mechanism by which lupus causes vasculitis?
immune complexes deposit in arterial walls, triggering local inflammation and damage.
vessel wall can necrose and/or thrombose, leading to ischemia/infarct
why is there ulnar deviation with lupus?
is there erosion of the joint spaces?
deviation due to intense articular inflammation: joint becomes loose, flopy –> tendons tug on the sides of the joint and cause deformity.
NO erosion at the joint space.
be able to distinguish RA v SLE with an xray of the hand.
which has joint space erosion?
see Bone Radiology for way better pics of each.
SLE - NO erosion
RA: joint space erosion
very generally, why does lupus cause renal disease?
what is the most common pattern of glomerular injury?
vasculitis: deposits of immune complexes in sub-endotheium. leads to inflammation –> leaky, pockmarked cells.
Pathoma: diffuse proliferative glomerulonephritis is most common pattern.
(Pic: L is normal glomerular tuft; R is lupus)
exactly where in the glomerulus are the immune complexes deposited with lupus renal disease?
-extensive subendothelial deposits (narrowest arrows)
plus subepithelial (A), intramembranous (B), basement membrane (C), foot processes (D)
what is the IF pattern of staining with lupus?
remember this from renal? ;)
Full House pattern (everything you stain for is positive)
Granular deposits rather than linear
what’s this disease? how is it different from lupus in terms of pattern of deposits?
linear immunofluorescence against the basement membrane.
Goodpasture’s Syndrome aka Anti-GBM disease.
In this disease, the glomerular BM is the target of the disease rather than being an innocent bystander, as with lupus
what’s seen at the longer arrows?
shorter arrows?
Long: mesangial cell proliferation
short: immune deposits -> wire loop lesions (upper left)
(there were a few more pics in the lecture that I don’t have time to upload. review if you have time! slides 74-83 or so)
how can immune complex deposition affect the lungs?
can lead to serositis–>
-pleuritis or pleurisy with pleural effusions
Note loss of costo-phrenic angle
how can lupus afect the heart?
serositis again?
- pericarditis with pericardial effusion
- abnormal heart border, less retrosternal heart space.
on ECHO, there is posterior and anterior pericardial effusion (arrows)
what’s this?
what can it cause?
Libman Sacks endocarditis.
small, sterile deposits on both sides of the mitral valve (chordae tendonae)
pieces of this vegetation can flick off and cause stroke.
what’s this?
Full House pattern seen with lupus IF staining. positive for everything! (IgG, C3, IgG, C1q…)
What is the theory of how APS causes clotting?
Antiphospholipid antibodies recognise beta-2 glycoprotein 1, which is involved in the normal immune system. (it’s a cofactor for Lupus Anticoagulant and Anti-Cardiolipin)
when the APS antibodies bind beta-2 glycoprotein, it changes conformation and can bind to other surface receptors, somehow leading to thrombosis.
(red = APS antibody, yellow = B2glycoprotein 1)
what are these?
identify each….
which is specific for CREST?
ANA patterns.
UL: periperal/rim
UR: homogeneous
LL: speckled (sometimes seen in scleroderma)
LR: nucleolar
CREST: centromere (looks speckled)
what is BLyS? what is its normal function?
it’s a B cell survival factor.
Signals to B cells that they should keep going! prevents them from apoptosing. Like those volunteers at the sidelines of road races who hand you gatorade.
