Autoimmunity (Organ-specific autoimmune disease) Flashcards by LEDESMA, Anne Gelika

diseases in which immune response is directed against self-antigens that are mainly found in a single organ/gland

Organ-Specific Autoimmune Diseases

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2 Autoimmune Thyroid Disease (AITDS)

Hashimoto’s thyroiditis (Chronic lymphocytic thyroiditis)
Graves disease

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associated alleles/HLA antigens in Hashimoto’s thyroiditis

HLA antigens DR3, DR4, DR5, DQ7

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associated allele/HLA antigen in Graves dse

HLA-DR3

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formed antibodies from the mutations in the thyroglobulin gene that allow for interaction of protein with HLADR antigens

antithyroglobulin antibodies

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history of Chronic lymphocytic thyroiditis

Japan, 1912
Dr. Hakaru Hashimoto

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most common autoimmune disease; what is the proportion?; W:M?

Hashimoto’s Thyroiditis (Chronic lymphocytic thyroiditis)
8 in every 1,000
5-10:1

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condition with a production of thyroid-specific autoantibodies and cytotoxic T cells

Hashimoto’s Thyroiditis

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associated with hypothyroidism

Hashimoto’s Thyroiditis

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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

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assoc with hyperthyroidism

Graves Disease

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S/S:
nervousness
insomnia
depression
weight loss
heat intolerance
sweating
rapid heartbeat
palpitations
breathlessness
fatigue
cardiac
dysrhythmias
restlessness

Graves Disease

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sign present in 35% of patients with Graves dse

Exophthalmos (hypertrophy of eye muscles and increased connective tissue in the orbit)

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express TSH receptor-like proteins affected by thyroid-stimulating immunoglobulin

Orbital fibroblasts

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Treatment for Autoimmune Thyroid Disease (AITDS)

daily oral thyroid hormone replacement therapy, with levothyroxine (T4)

radioactive iodine therapy, or surgery (thyroidectomy)

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Lab diagnosis for Autoimmune Thyroid Disease (AITDS)

TSH levels (chemiluminescent immunoassays - < 0.1 mU/L)

TSH Receptor Ab (TRAbs) – Graves dse

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selective destruction of beta cells of the pancreas; characterized by hyperglycemia

Type 1 Diabetes

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associated HLA gene in T1 diabetes

HLA-DR3 or DR4 gene

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T/F
hyperglycemia does not become evident until 80% or more of the beta cells are destroyed

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it is central to disease pathogenesis of T1 diabetes

autoimmunity to insulin

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Treatment for T1 diabetes

Daily injectable insulin
Beta Islet cell transplantation

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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%

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glycated form of hgb made when RBC protein combines with glucose in the blood.

HbA1c

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HbA1c reflects the average plasma glucose concentration over the previous _____

2-3 months

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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

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

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

Autoimmunity (Organ-specific autoimmune disease) Flashcards

(80 cards)