8) Autoimmune diseases Flashcards
predispositions to autoimmune conditions
- genetics
- female
- age
- mental state/stress
- infections
- drugs
- other autoimmune diseases
2 drugs that predispose pt to autoimmune disease
procainamide
hydralazine
how can trauma and infection predispose pt to autoimmune disease
release sequestered antigens
possible mechanisms of autoimmune disease
- loss of suppressor T cells
- MHC genes for molecules on cells they should not be on
- idiotypic networks (ab against ab)
example of an idiotypic network
RF
IgM against IgG
examples of disease with anti-idiotypic networks
myasthenia gravis
DM
Grave’s
organ systems affected by SLE
joints
CNS
heart
kidneys
cause of death in SLE
kidney lesions
type of scleroderma with increased collagen deposits in skin
progressive systemic sclerosis (PSS)
associated with Raynaud’s phenomenon
PSS
CREST
CREST syndrome
- calcinosis
- raynaud’s
- esophageal dysfunction
- sclerodactyly
- telengiectasis
components that attack joint spaces in RA
RFs
cytokines
IgG complexes
neutrophils
hyaluronidase
connective tissue disease with no renal involvement (5% pts may have it)
mixed connective tissue disorder (MCTD)
2 Ab involved in pernicious anemia
IF-blocking Ab
parietal cell Ab
autoimmune hepatitis involving smooth muscle Ab
chronic active hepatisis
very dry mouth, eyes, nose, trachea, bronchi, vagina, skin
large parotid glands
Sjogren’s syndrome
T-cells infiltrate muscle and cause inflammation
polymyositis
predominantly in young males
Goodpasture
glomerulonephritis
pulmonary hemorrhage
Ab to basement membrane of lungs, kidneys
Goodpasture
necrotizing granulomas in resp tract
focal glomerulonephritis
Wegener’s granulomatosis
2 autoimmune conditions involving skin blisters
bullous pemphigoid
pemphigus vulgaris
mitrochondrial Ab
bile ducts of liver slowly destroyed
liver damage
primary biliary cirrhosis
increased risk of clotting and repeated spontaneous abortions
anti-phospholipid syndrome
goiter
hypothyroidism
Hashimoto’s thyroiditis
goiter
ophthalmopathy
localized edema in legs
hyperthyroidism
Graves
2 types of anti-TSH receptor Ab
- stimulates action of TSH on thyroid
- blocks action of TSH on thyroid
Ab to NM junction (Ach receptor Ab)
weakness and fatigue of skeletal muscles
myasthenia gravis
causes most damage in MS
T-cells
autoab to plt
idiopathic/immune thrombocytopenia purpura
linear deposits of IgG/C3 at dermal-epidermal junction
bullous pemphigoid
honeycomb pattern of IgG/C3 in skin intercellular spaces
pemphigus vulgaris
ribbonlike pattern of Ab/C3 along glomerular basement membrane
Goodpasture
SLE
general indirect IFA autoimmune screen
ANA
anti nuclear Ab
3 Abs detected with mouse stomach-kidney substrate
- AMA (anti mitochondrial)
- ASMA (anti smooth muscle)
- APCA (anti parietal cell)
ANCA
anti neutrophil cytoplasmic ab
ANA test substrate & 5 patterns
HEP-2 (human epithelials in interphase/mitosis)
- homogeneous
- speckled
- centromere
- nucleolar
- rim/peripheral
entire nucleus fluoresces
mitotic cells pos
homogeneous
homogeneous pattern suggests…
ab to nDNA
reflex to anti-nDNA
homogeneous pattern diseases
SLE
drug-induced SLE (Ab to histones, ssDNA)
many uniform points of fluorescence
mitotic cells neg
speckled
speckled pattern suggests….
Ab to an extractable nuclear antigen (ENA)
reflex to ENA test
medium size points of fluorescence
mitotic cells pos in ladder-like pattern
centromere
centromere pattern disease
CREST syndrome
intense fluorescence of nucleoli
mitotic cells pos
nucleolar pattern
nucleolar pattern diseases
PSS
SLE
nucleus fluoresces around edge only
rim/peripheral pattern
rim pattern suggests…
ab to nDNA
rim pattern disease
SLE (most specific)
anti-nDNA substrate
crithidia lucillae
positive result in anti-nDNA test
fluorescence of kinetoplast of C. lucillae organism
positive anti-nDNA test diseases
active SLE
nephritis
nDNA Ab titer correlates with…
renal involvement
fluorescence of kidney tubules + parietal cells
ab and disease
AMA
primary biliary cirrhosis
fluorescence of stomach muscularis and vessel walls
ab and disease
ASMA
chronic active hepatitis
fluorescence of parietal cells
ab and disease
APCA
pernicious anemia
2 ANCA patterns
- C-ANCA - fluorescence of cytoplasm
- P-ANCA - fluorescence of perinuclear region
ANCA substrate
human neutrophils
C-ANCA disease
Wegener’s granulomatosis
P-ANCA disease
systemic vasculitis
explain EIA
solid phase + Ag + pt Ab + conjugate + enzyme + chromogenic substrate ==> color change
enzyme tag often on conjugate for EIA
horseradish peroxidase
EIA reading
spectrophotometric
ENAs and disease associations
- Sm (Smith) - SLE
- RNP (ribonucleoprotein) - MCTD, SLE
- SS-A (Ro) - Sjogren’s, scleroderma, SLE, neonatal lupus
- SS-B (La) - Sjogren’s, scleroderma, SLE
- Scl-70 - PSS
- PM-1 - polymyositis, SLE
- Jo-1 - polymyositis
associated with DVT, arterial thrombosis, spontaneous abortion
anti-PL ab
(LLAC, anti-cardiolipin)
seen in 90% of Hashimoto’s pts and 80% of Graves pts
thyroid peroxidase ab (TPO)
(microsomal ab)
seen in 60-80% of Hashimoto pts
thyroglobulin antibody (TGAB)
> 98% pts with Graves have…
thyroid stimulating Ig (TSI)
performed instead of expensive TPI test
TH levels
ideally use both ….. to dx RA
RF and anti-CCP
found in 75% pts with RA, but not specific for RA
RF
Ab against citrullinated peptides formed during death of grans and macros
anti-CCP
more specific for RA than RF
anti-CCP
ANAs are present in 40% of —– pts but significance is unknown
RA
