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.
