Autoimmune Diseases Flashcards
Hashiomoto’s Thyroiditis
- Chronic lymphocytic thyroiditis T cell response targets thyroid antigens
- (Anti-thyroglobulin – directed against thyroglobulin precursor in follicles
- Anti-thyroid peroxidase (anti-TPO) – directed against thyroid peroxidase in microsomes)
- Decreased production of thyroid hormones and uptake of thyroid hormone
- Result – hypothyroidism
- Autoantibodies also contribute to organ damage
Hashimoto’s Thyroiditis - Clinical Features
- Onset of disease – 30-60 years of age
- 5 times more common in♀than♂
- Linked to disease predisposition: HLA-DR3, HLA-DR4, and HLA-DR5
- Linked to protection from disease: HLA-DQB1
- Patients have low T4 and high TSH
- Prolonged hypothyroidism leads to myxedema Diagnosis- Autoantibodies can be detected by several methods: EIA, chemiluminescence, IFA (indirect immunofluorescence), hemagglutination
- Treatment – thyroid hormone replacement
Grave’s Disease
- Antibodies mimic TSH by binding to and activating TSH receptors
- Thyroglobulin breakdown accompanied by production of T4 and T3
- Result – hyperthyroidism
- Onset of disease – 20-50 years of age 10 times more common in♀than♂
- Lower incidence in African Americans vs. Caucasians In Caucasians, high risk may be linked to: DRB1*0304, DRB1*0301, or DQA1*0501
- Linked to protection from disease: DRB1*07
Laboratory Testing for Grave’s Disease
Diagnosis often made on clinical symptoms alone Elevated T3 and T4; low TSH >50% of patients have anti-TPO abs; some patients have low anti-thyroglobulin
Type 1 Diabetes Mellitus
- Also called insulin-dependent or juvenile diabetes 10% of diagnosed cases of diabetes in U.S.; chronic disease in children
- Abrupt onset in children <20 years old
- Now recognized as an autoimmune disease
- Patients have antibody to the insulin-producing cells (beta cells) in the pancreas
Type 1 Diabetes Pathophysiology
- A virus (Coxsackie B, rubella, rotavirus, or enterovirus) may initiate response: Antibodies cross-react with epitopes on pancreatic cells
- Macrophages and Th1 lymphocytes activated and release cytokines
- Atrophy and fibrosis of pancreas results
- Stimulate formation of autoantibodies to native insulin or islet cell antigen, resulting reaction of these autoantibodies with tissue antigen causes termination of insulin production and hyperglycemia.
Type 1 Diabetes Disease
Hyperglycemia, ketoacidosis, and eventual absolute insulin deficiency.
Laboratory Tests for Type 1 Diabetes
- Elevated serum and urine glucose
- Increased ketone excretion
- Decreased insulin levels in plasma
- Antibodies to native insulin may be detected in plasma
Multiple Sclerosis Causative Factors
- Progressive, relapsing inflammatory condition of CNS, leading to interruption of nerve impulses
- Environmental and genetic factors trigger autoimmune response
- Viruses such as EBV and HHV-6 suggested as causative agents
Multiple Sclerosis Disease
- Characteristic plaques appear within white matter of central nervous system damage myelin sheath; produced by: Interaction of myelin-reactive T cells and macrophages with myelin epitopes and Inflammatory reactions
- Peak incidence – 20-50 years of age
- Twice as many women as men affected
- Linked to disease predisposition: People of Northern European heritage HLA DRB1, DRB5, and DQB1
- Acute attacks alternate with remission
Multiple Sclerosis Treatment
Steroids may decrease immune reactions
Routine injections with beta interferons and synthetic myelin protein have shown success in some patients
Laboratory Testing for Multiple Sclerosis
History, neurological exam, MRI most commonly used CSF protein – normal or slightly elevated
High IgG in CSF compared to serum IgG
Autoimmune Hepatitis
Has developed in some patients following acute hepatitis A infection If untreated, can cause fulminant hepatitis or cirrhosis
Hepatocytes destroyed by: Cell-mediated toxicity involving IL-2 and TNF Antibody-dependent cytoxocity (ADCC) involving IL-4 and IL-10
Laboratory Testing for Autoimmune Hepatitis
- High alanine aminotransferase (ALT)
- High bilirubin
- Type I patients: High ANA antibodies; no characteristic pattern
- High anti-SMA Type II patients: High anti-LKM Significant titers of these antibodies: >1:80 (adults); 1:20 (children)
Primary Biliary Cirrhosis
Anti-mitochondrial antibodies (MA) to mitochondrial antigens (usually enzymes) destroy intrahepatic bile ducts
Onset of disease – 50s and 60s 90% of patients are women
Laboratory Testing for Primary Biliary Cirrhosis
Elevation of 1 or more liver enzymes: Alkaline phosphatase, gamma glutamyl transpeptidase, alanine aminotransferase, aspartamine aminotransferase Increased: bilirubin, cholesterol, ceruloplasmin, IgM, urine excretion of copper, 50% have increased ANA antibodies 90% of patients have high anti-MA Detected by indirect FA
Primary Sclerosing Colangitis
- Rare hepatic autoimmune disease
- Inflammation of intra- and extrahepatic bile ducts, leading to cirrhosis
- Often seen in patients with inflammatory bile diseases
Pernicious Anemia (Autoimmune)
- Autoantibody against intrinsic factor (IF) binds and inhibits absorption of vitamin B12
- Autoantibody to gastric parietal cells seen in 80% of patients
- Onset of disease – ~60 years of age
- Disease affects slightly more♀than♂
- Treatment: monthly B12 injections
Laboratory Tests for Pernicious Anemia
- Peripheral blood smear: Macrocytic, normochromic RBCs, Hypersegmented neutrophils, Frequent pancytopenia
- High MCV, High MCH; MCHC normal
- Low serum vitamin B12; normal folate
- Schilling’s test positive
- Fluorescent methods for anti-parietal antibodies
Systemic Autoimmune Diseases
- Autoantibodies that react with antigens in multiple cells/organs of the body
- Damage to collagen in vascular or connective tissue Immune complexes, autoantibodies, and acute inflammatory response cause most damage
- Laboratory Testing: CBC, metabolic panel, urinalysis, C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), test for rheumatoid factor, test for presence of antinuclear antibodies (ANA), complement levels
Rheumatoid Arthritis
- Chronic disease with inflammation and destruction of joints
- Probable cause – infection with virus (EBV) or bacterium
- Response to this foreign antigen attracts cells to the synovium; cytokines cause inflammatory response Immune complexes (IgM anti-IgG bound to IgG) in joint binds complement and attracts PMNs and macrophages
- Cytokines released from macrophages and lymphocytes, lysozymes, and other proteases from neutrophils damage the cartilage in the joint
- Treatment – non-steroidal anti-inflammatory drugs (NSAIDs) initially; as disease progresses, methotrexate, steroids, and biologic disease modifiers may be used
Laboratory Testing for Rheumatoid Arthritis
Nonspecific findings: Normochromic, normocytic anemia, low serum iron, high total protein, high ESR, positive CRP
Laboratory marker for RA – presence of rheumatoid factor; not specific for RA, but ~80% of people with RA have high RF Positive – >60 U/ml by nephelometry; titer of >1:80 by agglutination
Systemic Lupus Erythematosus
- Circulating immune complexes deposited in various tissues cause inflammation and destruction
- Joints, skin, kidney, brain, and lungs most commonly affected
- Treatment: NSAIDs, steroids, antimalarial drugs for joint pain, methotrexate
Sjogren’s Syndrome
- Pathological changes in salivary and lachrimal glands
- Can be a primary disease or secondary to another autoimmune condition or triggered by a viral infection Usually mild, but may become systemic
- Patients may have high risk of malignant B cell lymphoma Immune reaction leads to chronic inflammation of salivary gland
- Treatment – drugs to stimulate flow of saliva, artificial tears
Laboratory Testing for Sjogren’s Syndrome
Diagnosis usually based on symptoms
Biopsy of salivary gland – classic inflammation with T and B cells
ANA with speckled pattern - 70% of patients are positive, typically of anti-SS-A/Ro or anti-SS-B/La
Primary Immunodeficiencies
- Severe combined immunodeficiency (SCID) is the most severe
- Pure T cell disorders also usually severe since cytokines are important to the immune response
- Pure B cell disorders are characterized by frequent serious bacterial infections
SCID
- Both T and B cell deficiency
- Usually recognized in neonatal period Patient experiences failure to thrive, diarrhea, and persistent infections, Skin lesions common
- Diagnosis – clinical symptoms, small thymus, hypogammaglobulinemia, profound lymphopenia
SCID Treatment
Bone marrow or hematopoietic stem cell transplant 95% cure rate if performed in first 3 months of life
Secondary Immunodeficiencies
Due to an exogenous agent or condition HIV, severe nutritional defects, burns, chemotherapy Immunodeficiency not always permanent
Rheumatoid factor
- A diverse group of immunoglobulins occurring in patients with rheumatoid arthritis, specifically these antibodies (mostly IgM) react with the Fc regions of IgG molecules
- Positive reactions depend on the antigenic multivalency of IgG achieved by aggregation
- They are not disease specific and can occur in situations of chronic inflammatory disease such as bacterial endocarditis, tuberculosis, and leprosy
C3 and C4
- Depressed levels indicate SLE and liver disease
- Depressed C3 and normal C4 indicate acute poststreptococcal glomerulonephritis and PNH, The reverse is true for membranoproliferative glomerulonephritis and some coagulopathies
- C4 is reduced in patients with rheumatoid arthritis
CSF IgG in MS
There is a 30 to 40% false positive rate when applied to patients with meningitis (aseptic and carcinomatous), cerebral lymphoma, encephalitis, syphilis, Guillain Barre syndrome, post viral myelitis, cerebral arthritis, cerebral lupus erythematosus
Primary Sclerosing Colangitis Laboratory testing
- Not specific
- Increased IgM
- Increased p-ANCA antibodies (not specific for PSC)
