autoimmune disorders Flashcards
What happens during central tolerance in the thymus?
T-cells undergo apoptosis or become regulatory T cells.
AIRE mutations can lead to autoimmune polyendocrine syndrome
What is peripheral tolerance?
Anergy or apoptosis of T and B cells to prevent autoimmunity.
What happens during central tolerance in the bone marrow?
B-cells undergo receptor editing or apoptosis.
What is the result of Fas apoptosis pathway mutations?
Autoimmune lymphoproliferative syndrome (ALPS).
How do regulatory T cells suppress autoimmunity?
By blocking T-cell activation and producing anti-inflammatory cytokines like IL-10 and TGF-β.
What are CD25 polymorphisms associated with?
Autoimmunity, particularly in diseases like Multiple Sclerosis (MS) and Type 1 Diabetes (DM).
What happens due to FOXP3 mutations?
Leads to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).
In which gender are autoimmune diseases more common?
Women, particularly those of childbearing age.
How does estrogen affect autoimmunity?
Estrogen may reduce apoptosis of self-reactive B cells, potentially contributing to autoimmune diseases.
What is the likely etiology of autoimmune diseases?
Environmental triggers in genetically-susceptible individuals.
What is the incidence of autoimmune diseases in twins?
There is an increased incidence of autoimmune diseases in twins
What HLA type and polymorphisms are associated with autoimmune diseases?
HLA-B27 and PTPN22 polymorphisms.
What triggers autoimmune diseases?
Environmental triggers lead to bystander activation or molecular mimicry.
How do autoimmune disorders typically progress?
They are clinically progressive with relapses and remissions, often showing overlapping features, which is partially explained by epitope spreading.
What is Systemic Lupus Erythematosus (SLE)?
A chronic, systemic autoimmune disease characterized by flares and remissions.
Who is most commonly affected by Systemic Lupus Erythematosus (SLE)?
Middle-aged females, particularly African American and Hispanic women. It can also affect children and older adults (with less gender bias).
What is the pathophysiology of Systemic Lupus Erythematosus (SLE)?
Antigen-antibody complexes damage multiple tissues (type III hypersensitivity reaction).
Poorly-cleared apoptotic debris activates self-reactive lymphocytes, leading to the production of antibodies against nuclear antigens.
These complexes deposit in multiple tissues, causing damage.
What role do complement proteins play in SLE?
Deficiency of early complement proteins (C1q, C4, and C2) is associated with SLE
What are the classic findings in Systemic Lupus Erythematosus (SLE)?
Fever, weight loss, fatigue, lymphadenopathy, and Raynaud phenomenon.
Malar butterfly rash or discoid rash, especially after sunlight exposure.
Oral or nasopharyngeal ulcers (usually painless).
Arthritis (usually involving ≥ 2 joints).
Serositis (pleuritis and pericarditis).
Psychosis or seizures.
Renal damage (e.g., diffuse proliferative glomerulonephritis).
Anemia, thrombocytopenia, or leukopenia (type II hypersensitivity reaction).
Libman-Sacks endocarditis.
What are the kidney-related findings in SLE?
Diffuse proliferative glomerulonephritis is the most common and severe form of renal injury in SLE. Other patterns include membranous glomerulonephritis.
What lab findings are characteristic of Systemic Lupus Erythematosus (SLE)?
Antinuclear antibodies (ANA) – sensitive but not specific.
Anti-dsDNA or anti-Sm antibodies – highly specific for SLE.
What is the relationship between antiphospholipid antibodies and SLE?
Antiphospholipid antibodies are present in one-third of patients with SLE and are autoantibodies directed against proteins bound to phospholipids.
What are the important antiphospholipid antibodies in autoimmune diseases?
Anticardiolipin, anti-β2-glycoprotein I, and lupus anticoagulant (which causes falsely-elevated PTT).
What is antiphospholipid antibody syndrome characterized by?
It is characterized by a hypercoagulable state due to antiphospholipid antibodies, leading to arterial and venous thrombosis, including deep venous, hepatic vein, placental (recurrent pregnancy loss), and cerebral (stroke) thrombosis.
What is the treatment for antiphospholipid antibody syndrome?
Requires lifelong anticoagulation.
What autoimmune disorder is associated with antiphospholipid antibody syndrome?
Systemic Lupus Erythematosus (SLE), although it more commonly occurs as a primary disorder
What is drug-induced lupus characterized by and what drrugs are associatedd with it?
Antihistone antibody is characteristic, and it is typically caused by drugs like procainamide, hydralazine, and isoniazid. ANA is positive by definition, but CNS and renal involvement are rare. Stopping the drug usually results in remission.
What is the first-line treatment for Systemic Lupus Erythematosus (SLE)?
Avoiding direct sunlight and using glucocorticoids for flares. Other immunosuppressive agents are used in severe or refractory disease.
What is the 5-year survival rate for Systemic Lupus Erythematosus (SLE)?
The 5-year survival rate is > 90%, but renal failure, infection, and accelerated coronary atherosclerosis (which occurs later) are common causes of death.
What is Sjögren Syndrome?
Autoimmune destruction of lacrimal and salivary glands, leading to dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia).
What age group is most commonly affected by Sjögren Syndrome?
Older women (ages 50-60 years).
What are the main diagnostic criteria for Sjögren Syndrome?
ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro and anti-SSB/La).
Lymphocytic sialadenitis (inflammation of salivary glands) on lip biopsy.
What is the risk for pregnant women with anti-SSA antibodies?
Pregnant women with anti-SSA antibodies are at risk of delivering babies with neonatal lupus and congenital heart block.
What is the increased risk in Sjögren Syndrome?
Increased risk for B-cell (marginal zone) lymphoma, which presents as unilateral enlargement of the parotid gland late in the disease.
What is Systemic Sclerosis (Scleroderma)?
An autoimmune disorder characterized by sclerosis of the skin and visceral organs, commonly affecting middle-aged females (ages 30-50 years)
What causes the fibrosis seen in Systemic Sclerosis (Scleroderma)?
Fibroblast activation leads to collagen deposition. Endothelial dysfunction and secretion of growth factors (e.g., TGF-β and PDGF) cause fibrosis and organ damage.
What is Limited Type systemic sclerosis (scleroderma) and what antibody is it associated with?
Limited skin involvement (hands and face) with late visceral involvement. The prototype is CREST syndrome, which includes:
Calcinosis (calcium deposits)
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly (tightening of skin on fingers)
Telangiectasias (small blood vessels)
Associated with anti-centromere antibodies.
What is Diffuse Type systemic sclerosis (scleroderma) and what antibody is it associated with ?
Diffuse skin involvement with early visceral involvement. Any organ can be involved, and common organs include:
Vessels (Raynaud phenomenon)
GI tract (esophageal dysmotility, reflux)
Lungs (interstitial fibrosis, pulmonary hypertension)
Kidneys (scleroderma renal crisis)
Anti-Scl-70 antibodies (highly associated).
What is Mixed Connective Tissue Disease (MCTD) and what antibody is it associated with?
An autoimmune disease that shows mixed features of SLE, systemic sclerosis, and polymyositis.
Characterized by ANA and serum antibodies to U1 ribonucleoprotein.
what happens if there is a defect in central tolerance ?
autoimmune polyendocrine syndrome type 1
what happens if there is a defect in peripheral tolerance ?
immune dysregulation syndrome ( IPEX syndrome due to FOXP3 mutation )
What kind of endocarditis is associated with SLE ?
Libman-Sacks endocarditis.
