Systemic Autoimmune Diseases Flashcards
SLE stands for
systemic lupus erythematsus
SLE mainly by what HSR
III
not a diagnostic autoantibody for
rheumatic diseases
SLE is most common
autoimmune rheumatic disease
why is complement pathway involved in SLE
they are involved in removing immune complexes
what is enviornmental trigger of SLE
UV light
deposition of immune complexes where in SLE
glomeruli & blood vessels
deposition of blood vessels in immune complexes are what give rise to
the rash (well known)
hemorrhaging of small blood vessels in skin give rise to what rash in SLE
butterfly/malar
what does SLE affect
everywehre - could eventually lead to organ failure and even death
symptoms of SLE
arthirtis, skin rashes (butterfly rash), pleurisy, kidney dysfunction, fever, weakness, anemia, thrombocytopenia, memory loss, headaches, confusion, seizures
treatment of SLE
immunosuppressive drugs, but SLE is a relapsing and remitting disease, so treatment is variable
what are triggers of SLE
UV
cigarette smoke
how can you diagnose SLE
ANA - antinuclear antibody (but most rheumatic diseases have this)
anti-SnRNP or smith antigen
ANA stand for
anti-nuclear antibody
most individuals with rheumatic disease will have
ANA
Rheumatoid Arthritis is chronic, episodic
joint inflammation
Rheumatoid Arthritis is due to what HSR
III and IV
what cells are responsible for inflammation in jionts in Rheumatoid Arthritis
neutrophils
what are the autoreactive cells in Rheumatoid Arthritis
CD4+ Th1 cells & Th17 cells
key cytokine in Rheumatoid Arthritis
TNF alpha
key cytokines in Rheumatoid Arthritis
IL-1
TNF alpha
prostaglandins
leukotrienes
Th17 cells will activate what that will be responsible for remodeling of bone in chronic Rheumatoid Arthritis
osteoclastst
what autoantibody is in Rheumatoid Arthritis
rheumatoid factor
rheumatoid factor is what isotype
IgM
rheumatoid factor not good for diagnosis b/c
only 70% pts with Rheumatoid Arthritis have it
detection of rheumatoid factor is useful in Rheumatoid Arthritis b/c it can be useful in
predicting outcome/prognosis of disease
pts who have rheumatoid factor in serum with Rheumatoid Arthritis tend to have (RF+)
more aggressive disease
test to detect RF is based on
agglutination
describe test to detect RF
latex particles that chemically coated with IgG
add pts serum
if pt has RF in serum it will bind to IgG and nbe very good at agglutination b/c IgM has 10 binding sites
so if pt does have RF in serum will see agglutination of serum
what is target antigen of RF
IgG
RF stands for
rheumatoid factor
test to detect RF and autoantibodies against any given autoantigen relies on activation of
complement
complement fixation test does what
detects if pt has antibody for particular antigen
fixation is old term for
ACTIVATION OF COMPLEMENT
describe complement fixation test
mix Ag with serum
add complement, a fixed amount
if antibody has bound to antigen complement will be activated
once complement is activated, will use up the fixed amount
to determine if complement is used up add indicator cells (RBC coated with antibody)
if antibody has not bound to the antigen the complement will not be used up and will be available to activation by cells that are coated with antibody (RBC) so in other words if in original tube there is not antibody specific for antigen, the complmeent is available for the RBC and will get lysis of RBC
if it is positive test and individual has antibody against antigen, the complement will b used up and no complement available to be activated on indicator cells (RBC) so no lysis of RBC
amount of erythrocyte lysis tell you if you have antibody specific for antigen
the important thing about the complement fixation test is that you add
limited amount of complement
negative result in complement fixation test, what is result
lysis of RBC
positive result of complement fixation test
no lysis of RBC, fixation of RBC
initiating factor of Rheumatoid Arthritis
don’t know :(
might be multiple things, different for different ppl
Rheumatoid Arthritis results in infltration f
Th1 and Th17 into joint
Th1 and Th17 activate what in Rheumatoid Arthritis
macrophages, fibroblasts, osteoclasts
during Rheumatoid Arthritis what happens to synovial membrane
thickened due to infiltration of inflammatory cells into membrane and into synovial fluid
outgrowth from synovial membrane in Rheumatoid Arthritis what is it called
pannus
what is in pannus* high yield
lots of neutrophils
how do diagnose Rheumatoid Arthritis
no single test - based on clinical assessment, X-Ray
RF test
new test more specific than RF to test for cyclic citrullinated peptides
treatments for Rheumatoid Arthritis
physiotherapy
immunosuppressive drugs
TNF alpha inhibitors
anti-CD20 mAb
rewview pg 20
20
CRP is ___ __ protein
acute phase
CRP levels increase during
inflamamtion
CRP decrease is consistent with decrease in
inflammation
pts with Rheumatoid Arthritis that don’t respond to TNF alpha treatment will usually respond to
antiCD20 treatment
Sjogren’s syndrome is probably what HSR
IV
sjogren’s syndrome more common in women ormen
women
what is most comon rheumatic disease besides SLE
sjogren’s
what causes sjogren’s syndrome
autoimmune destruction of exocrine glands - often lacrimal and salivary glands
parotid gland of pt with sjogren’s is full of
CD4+ T cells and b cells
symptoms of sjogren’s syndrome depend on
exocrine glands affected
symptoms of sjogren’s syndrome
Symptoms are highly variable
Dry eyes - decreased production of tears, red eyes
Dry mouth - decreased production of saliva, difficulty swallowing, cracking of lips and/or tongue
Dry skin, nose, throat, vagina
Joint pain, skin rash
diagnosis for sjogren’s syndrome
Shirmer’s Test, to test tear production
Spit Test
Autoantibodies = ANA (anti-Ro, -La) and RF
Biopsy of enlarged gland
RF is present in
many auto-rheumatic diseases
autoantibodies most useful in detecting sjogren’s
anti-Ro, -La
Granulomatosis with Polyangiitis is due to what response
Th1
autoantibody associated with Granulomatosis with Polyangiitis
anti-neutrophil cytoplasmic autoantibodies (ANCA)
antigen recognized by anti-neutrophil cytoplasmic autoantibodies (ANCA)
PR3 (proteinase 3)
they think might have some disease/infection before Granulomatosis with Polyangiitis why
b/c of the granuloma that forms
describe mechanism of Granulomatosis with Polyangiitis
uptake of autoantigen by dendritic cells
autoantigen seems to be proteinase 3
autoantigen taken to lymph which stimulates CD4 to differentiate into Th1
Th1 activate marophaegs at site of infection
formation of granuloma
T cells can provide help to b cells to make autoantibody
proteinase 3 is released when
when neutrophils undergo netosis
Vasculitis in GP what is initiating antigen
PR3
in Vasculitis in GP autoantibodies stimulate the ___ of neutrophils
degranulation
symptoms of Granulomatosis with Polyangiitis
Airway Symptoms: rhinitis, cough, chest pain,
sinusitis, congestion
Kidney disease, due to glomerulonephritis
Saddle nose, due to cartilage damage in bridge
diagnosis of Granulomatosis with Polyangiitis
detect serum anti-PRS ANCA - the most specific
can also do x0ray, etc
review pg 29
29
Ankylosing Spondylitis is unusual b/c
ratio of males to females - 90% male
Ankylosing Spondylitis has very strong association with
HLA-B27
features of Ankylosing Spondylitis
fusion of vertebrae at base of spine - lose S shape curvature
clinical freatures of Ankylosing Spondylitis
Pain and stiffness in lower back and hips
Chronic synovitis (esp. Achilles)
20% have other HLA-B27-associated arthritides: Reactive Arthritis or Reiter’s syndrome
treatment of Pain and stiffness in lower back and hips
Chronic synovitis (esp. Achilles)
20% have other HLA-B27-associated arthritides: Reactive Arthritis or Reiter’s syndrome
anti-TNF mAbs (or drugs to inhibit activity of TNF)
role of HLA-B27 in Ankylosing Spondylitis
4 different theories
presentation of disease associated peptides by B27 - proposes that disease associated B27 alleles present peptide and recogniztion of peptide is what leads to arthritis
disease associated alleles cannot present peptide, failure to respond against pathogen that leads to development of Ankylosing Spondylitis
misfolded HLA-B27 on cell surface and in ER
one theory says misfolded on cell surface reocnigzed by NK and T cells
other theory says misfolded on ER triggers secretion f proinflammatory cytokines (unfolded protein response)
they don’tk now how it contributes
Scleroderma blood vessels involved look like
chronic graft rejection
features of blood vessles in Scleroderma
proliferation of smooth muscle cells infiltration of B and T cells imune complexes fibrosis of blood vessels just like chornic graft rejection
features of Scleroderma
occlusion of blood vessels - called raynaud’s syndrome
tightening of skin - sclerodactyll
digital ulcers
limited cutaneous form of Scleroderma
restricted to skin on hands, arms, face, feet
diffuse cutaneous form of scleroderma
more servere:
extensive skin + internal organ(s)
lung, kidney, heart, GI diseases
complications: pulmonary fibrosis; pulmonary hypertension
diagnosis of scleroderma
anti-nuclear autoantibodies (ANA)
RF+
review slide 35
35
omab means
only mouse
ximab means
mouse/human chimera
zumab means
humanized - almsot all human except CDR
mumab means
fully human
what is the target for SLE
skin
joints
kidneys
nervous system
what type of HSR for SLE
III
what are the autoantibodies for SLE
Anti-Sm
Anti-Ro
Anti-La
what is the target for Rheumatoid arthritis
joints
blood vessels
what is HSR for rheumatoid arthritis
III & IV
autoantibodies for rheumatoid arthritis?
Anti-CCP
RF
what is the target for scleroderma
skin
lungs
kidneys
heart
what are the autoantibodies for scleroderma?
anti-centromere
anti-ro
anti-RNP
what is the target for Ankylosing spondylitis
axial skeleton
peripheral joints
eye
what is the HLA for Ankylosing spondylitis
B27
what is the target for Granulomatosis with polyangiitis (WG)
kidneys
lungs
joints
skin
what is HSR for Granulomatosis with polyangiitis (WG)
II
what are autoantibodies for Granulomatosis with polyangiitis (WG)
anti-proteinase 3
what is target for sjogren’s syndrome
exocrine glands
what is HSR for sjogrens syndrome
IV
what are autoantibodies for sjogrens syndrome
anti-Ro
Anti-La
RF
