Autoimmunity (Organ-specific autoimmune disease) Flashcards
diseases in which immune response is directed against self-antigens that are mainly found in a single organ/gland
Organ-Specific Autoimmune Diseases
2 Autoimmune Thyroid Disease (AITDS)
Hashimoto’s thyroiditis (Chronic lymphocytic thyroiditis)
Graves disease
associated alleles/HLA antigens in Hashimoto’s thyroiditis
HLA antigens DR3, DR4, DR5, DQ7
associated allele/HLA antigen in Graves dse
HLA-DR3
formed antibodies from the mutations in the thyroglobulin gene that allow for interaction of protein with HLADR antigens
antithyroglobulin antibodies
history of Chronic lymphocytic thyroiditis
Japan, 1912
Dr. Hakaru Hashimoto
most common autoimmune disease; what is the proportion?; W:M?
Hashimoto’s Thyroiditis (Chronic lymphocytic thyroiditis)
8 in every 1,000
5-10:1
condition with a production of thyroid-specific autoantibodies and cytotoxic T cells
Hashimoto’s Thyroiditis
associated with hypothyroidism
Hashimoto’s Thyroiditis
S/S:
dry skin
decreased sweating
puffy face with edematous eyelids
pallor with a yellow tinge
weight gain
fatigue
dry and brittle hair
Hashimoto’s Thyroiditis
assoc with hyperthyroidism
Graves Disease
S/S:
nervousness
insomnia
depression
weight loss
heat intolerance
sweating
rapid heartbeat
palpitations
breathlessness
fatigue
cardiac
dysrhythmias
restlessness
Graves Disease
sign present in 35% of patients with Graves dse
Exophthalmos (hypertrophy of eye muscles and increased connective tissue in the orbit)
express TSH receptor-like proteins affected by thyroid-stimulating immunoglobulin
Orbital fibroblasts
Treatment for Autoimmune Thyroid Disease (AITDS)
daily oral thyroid hormone replacement therapy, with levothyroxine (T4)
radioactive iodine therapy, or surgery (thyroidectomy)
Lab diagnosis for Autoimmune Thyroid Disease (AITDS)
TSH levels (chemiluminescent immunoassays - < 0.1 mU/L)
TSH Receptor Ab (TRAbs) – Graves dse
selective destruction of beta cells of the pancreas; characterized by hyperglycemia
Type 1 Diabetes
associated HLA gene in T1 diabetes
HLA-DR3 or DR4 gene
T/F
hyperglycemia does not become evident until 80% or more of the beta cells are destroyed
T
it is central to disease pathogenesis of T1 diabetes
autoimmunity to insulin
Treatment for T1 diabetes
Daily injectable insulin
Beta Islet cell transplantation
How is T1 diabetes diagnosed?
if 1 of 4 criteria is met:
1. fasting glucose >126 mg/dL on <1 occasion (normal: < 100 mg/dL)
2. random plasma glucose level of >200 mg/dL with classic symptoms of diabetes
3. oral glucose tolerance test of >200 mg/dL in a 2-hour sample with a 75 g glucose load
4. hemoglobin A1c value (HbA1c) >6.5%
glycated form of hgb made when RBC protein combines with glucose in the blood.
HbA1c
HbA1c reflects the average plasma glucose concentration over the previous _____
2-3 months
Used for Confirmation of T1 diabetes diagnosis
antibodies to:
glutamic acid decarboxylase (GAD)
insulinoma-antigen 2 antibodies (IA-2A)
most sensitive tests and best positive predictive value for T1D in high-risk populations
Combined screening for IA-2A, ICA, GAD Ab
autoimmune disease affecting small intestine and other organs
Celiac Disease
Celiac Disease is associated with this known environmental trigger
dietary gluten
alleles in celiac disease
HLA-DQ2 (90% to 95%)
HLA-DQ8
W:M in celiac dse
2-3:1
what makes celiac dse difficult of diagnose?
extraintestinal manifestations in older children, teenagers, adults
Treatment for Celiac dse
gluten-free diet
Laboratory Diagnosis for Celiac dse
IgA Ab detection to tTG
biopsy of the small intestine
HLA typing
serological method of choice for initial testing (ELISA based) of Celiac dse
IgA Ab detection to tissue transglutaminase (tTG)
3 Autoimmune Liver Diseases
autoimmune hepatitis (AIH) / chronic active hepatitis
primary biliary cirrhosis (PBC)
primary sclerosing cholangitis (PSC)
immune mediated liver disease that can lead to endstage liver failure if left untreated
Autoimmune Hepatitis (AIH)
2 types of AIH differentiated on the basis of its autoantibody specificity
AIH-1
AIH-2
2/3 of all AIH cases; W:M ratio = 4:1
AIH-1
W:M ratio = 10:1; seen mostly in children
AIH-2
alleles associated with a higher risk of developing AIH
HLA-DRB1 and HLA-DQB1
necessary to confirm the diagnosis of AIH and to assess the extent of liver damage
Liver biopsy
Treatment of AIH
standard immunosuppressive treatment of prednisolone (+/–azathioprine)
liver transplant
most common autoimmune liver disease
Primary Biliary Cirrhosis (PBC)
W:M of Primary Biliary Cirrhosis (PBC)
10:1
haplotypes of Primary Biliary Cirrhosis (PBC)
HLA-DQA1
HLA-DQB1
HLADPB1
HLA-DRB1
involves progressive destruction of intrahepatic bile ducts
Primary Biliary Cirrhosis (PBC)
progressive destruction of intrahepatic bile ducts in Primary Biliary Cirrhosis (PBC) leads to
chronic cholestasis (flow of bile is slowed or blocked)
manifestation of later stages of PBC
jaundice
ascites
greasy stools
Treatment of PBC
ursodeoxycholic acid (UDCA)
liver transplant
Diagnosis of PBC
Anti-mitochondrial antibodies (AMAs) - IIF and ELISA
Elevated alkaline phosphatase - 1.5X the upper limit of normal for 6 months or more
liver biopsy showing nonsuppurative destructive cholangitis and
interlobular bile duct injury
autoimmune disorder involving CNS inflammation and destruction
Multiple Sclerosis
Multiple Sclerosis most closely associated with inheritance of a particular HLA molecule coding for beta chain of the DR subregion, namely
DRB1*1501
environmental factors associated with MS
reduced sunlight exposure
vit D deficiency
cigarette smoking
formation of lesions in MS in the white matter of brain and spinal cord, resulting in the progressive destruction of the myelin sheath of axons
plaques
specialized phagocytes of CNS
microglial cells
sensory abnormalities of MS
tingling or “pins and needles”
flashes of light seen on eye movement
W:M of MS
2:1
Treatment of MS
corticosteroids (reduce inflammation)
IFN-β1a and IFN-β1b (downregulate MHC molecules on APC)
natalizumab (humanized monoclonal Ab)
Laboratory Diagnosis of Multiple Sclerosis
protein electrophoresis and immunoblotting (oligoclonal)
IgG index = CSF IgG/albumin ÷ serum IgG/albumin (elevated)
autoimmune dse that affects neuromuscular junction; weakness and fatigability of skeletal muscles
Myasthenia Gravis (MG)
antibody-mediated damage to acetylcholine receptors in skeletal muscle
Myasthenia Gravis (MG)
S/S
ptosis (drooping of the eyelids)
diplopia (double vision)
inability to retract corners of mouth: snarling appearance
muscle weakness - most noticeable in the upper limbs
Myasthenia Gravis (MG)
antibody to acetylcholine (ACH) receptors (ACHR) in 80-85% of patients
MG
HLA haplotype that has a strong association with early onset MG (EOMG)
A1
B8
DR3
HLA haplotype which more likely to appear in late onset (LOMG)
B7
DR2
HLA that may increase susceptibility to muscle-specific kinase (MuSK) antibody production in MG
HLA-DR14-DQ5
Treatment of MG
Anticholinesterase agents (prevent destruction of neurotransmitter – acetylcholine)
Thymectomy on patients with thymoma
Plasmapheresis or IV immunoglobulin
Monoclonal antibodies or fusion proteins
Lab Dx of MG
radioimmunoprecipitation (RIPA) assay - detected with a radio-labeled snake venom called α-bungaro-toxin)
immunofluorescence cell-based assays (patient serum is incubated with HEK293 cells expressing all 4 ACHR subunits)
ELISA, luciferase immunoprecipitation, fluorescence immunoprecipitation assays (FIPA)
presence of autoantibody to an antigen in the basement membranes in the glomeruli of kidneys and alveoli of lungs
Good Pasture’s Syndrome
Good Pasture’s Syndrome affects these 2 age grp
men in 30s
men & women in 60s and 70s
rare disorder found mainly in Caucasians of European origin
Good Pasture’s Syndrome
S/S: fatigue and malaise followed by clinical signs of kidney involvement such as edema and hypertension, which can rapidly progress to acute renal failure if left untreated; 60 – 70% of patients have pulmonary involvement and exhibit symptoms such as cough, shortness of breath, hemoptysis (coughing up blood)
Good Pasture’s Syndrome
Treatment of GPS
high dose corticosteroids –> immunosuppressive drugs (cyclophosphamide)
plasmapheresis
lifetime hemodialysis or kidney transplantation
HLA antigen carried by GPS patients
HLA-DRB1-15
Etiology involves exposure to cigarette smoke & organic solvents; autoantibodies are specifically directed against noncollagenous domain of alpha-3 chain of type IV collagen; this autoantibody reacts with collagen in glomerular or alveolar basement membranes and causes damage by type II hypersensitivity
GPS
Lab Dx of GPS
▪ gross or microscopic hematuria
▪ proteinuria
▪ decreased 24-hour creatinine clearance
▪ elevated blood urea and serum creatinine levels
▪ abnormally shaped RBCs and casts in urine sediment
Circulating antibodies to GBM (Goodpasture Basement Membrane) can be identified through
IIF
ELISA
Western Blot
T/F
ANCAs may be detectable months to years before antiGBM and symptoms are evident
T
pattern formed of patient with GPS condition in direct immunofluorescence of kidney and lung specimen
smooth, linear, ribbonlike
glomerulonephritis pattern on immunofluorescence? reason?
granular
nonspecific deposition of immune complexes in the glomeruli
