autoimmune disorders

Question 1

What happens during central tolerance in the thymus?

Answer 1

T-cells undergo apoptosis or become regulatory T cells.
AIRE mutations can lead to autoimmune polyendocrine syndrome

Question 2

What is peripheral tolerance?

Answer 2

Anergy or apoptosis of T and B cells to prevent autoimmunity.

Question 2

What happens during central tolerance in the bone marrow?

Answer 2

B-cells undergo receptor editing or apoptosis.

Question 2

What is the result of Fas apoptosis pathway mutations?

Answer 2

Autoimmune lymphoproliferative syndrome (ALPS).

Question 3

How do regulatory T cells suppress autoimmunity?

Answer 3

By blocking T-cell activation and producing anti-inflammatory cytokines like IL-10 and TGF-β.

Question 4

What are CD25 polymorphisms associated with?

Answer 4

Autoimmunity, particularly in diseases like Multiple Sclerosis (MS) and Type 1 Diabetes (DM).

Question 5

What happens due to FOXP3 mutations?

Answer 5

Leads to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).

Question 6

In which gender are autoimmune diseases more common?

Answer 6

Women, particularly those of childbearing age.

Question 7

How does estrogen affect autoimmunity?

Answer 7

Estrogen may reduce apoptosis of self-reactive B cells, potentially contributing to autoimmune diseases.

Question 8

What is the likely etiology of autoimmune diseases?

Answer 8

Environmental triggers in genetically-susceptible individuals.

Question 9

What is the incidence of autoimmune diseases in twins?

Answer 9

There is an increased incidence of autoimmune diseases in twins

Question 10

What HLA type and polymorphisms are associated with autoimmune diseases?

Answer 10

HLA-B27 and PTPN22 polymorphisms.

Question 11

What triggers autoimmune diseases?

Answer 11

Environmental triggers lead to bystander activation or molecular mimicry.

Question 12

How do autoimmune disorders typically progress?

Answer 12

They are clinically progressive with relapses and remissions, often showing overlapping features, which is partially explained by epitope spreading.

Question 13

What is Systemic Lupus Erythematosus (SLE)?

Answer 13

A chronic, systemic autoimmune disease characterized by flares and remissions.

Question 14

Who is most commonly affected by Systemic Lupus Erythematosus (SLE)?

Answer 14

Middle-aged females, particularly African American and Hispanic women. It can also affect children and older adults (with less gender bias).

Question 15

What is the pathophysiology of Systemic Lupus Erythematosus (SLE)?

Answer 15

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.

Question 16

What role do complement proteins play in SLE?

Answer 16

Deficiency of early complement proteins (C1q, C4, and C2) is associated with SLE

Question 17

What are the classic findings in Systemic Lupus Erythematosus (SLE)?

Answer 17

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.

Question 18

What are the kidney-related findings in SLE?

Answer 18

Diffuse proliferative glomerulonephritis is the most common and severe form of renal injury in SLE. Other patterns include membranous glomerulonephritis.

Question 19

What lab findings are characteristic of Systemic Lupus Erythematosus (SLE)?

Answer 19

Antinuclear antibodies (ANA) – sensitive but not specific.
Anti-dsDNA or anti-Sm antibodies – highly specific for SLE.

Question 20

What is the relationship between antiphospholipid antibodies and SLE?

Answer 20

Antiphospholipid antibodies are present in one-third of patients with SLE and are autoantibodies directed against proteins bound to phospholipids.

Question 21

What are the important antiphospholipid antibodies in autoimmune diseases?

Answer 21

Anticardiolipin, anti-β2-glycoprotein I, and lupus anticoagulant (which causes falsely-elevated PTT).

Question 22

What is antiphospholipid antibody syndrome characterized by?

Answer 22

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.

Question 23

What is the treatment for antiphospholipid antibody syndrome?

Answer 23

Requires lifelong anticoagulation.

Question 24

What autoimmune disorder is associated with antiphospholipid antibody syndrome?

Answer 24

Systemic Lupus Erythematosus (SLE), although it more commonly occurs as a primary disorder

Question 25

What is drug-induced lupus characterized by?

Answer 25

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.

Question 26

What is the first-line treatment for Systemic Lupus Erythematosus (SLE)?

Answer 26

Avoiding direct sunlight and using glucocorticoids for flares. Other immunosuppressive agents are used in severe or refractory disease.

Question 27

What is the 5-year survival rate for Systemic Lupus Erythematosus (SLE)?

Answer 27

The 5-year survival rate is > 90%, but renal failure, infection, and accelerated coronary atherosclerosis (which occurs later) are common causes of death.

Question 28

What is Sjögren Syndrome?

Answer 28

Autoimmune destruction of lacrimal and salivary glands, leading to dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia).

Question 29

What age group is most commonly affected by Sjögren Syndrome?

Answer 29

Older women (ages 50-60 years).

Question 30

What are the main diagnostic criteria for Sjögren Syndrome?

Answer 30

ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro and anti-SSB/La).

Lymphocytic sialadenitis (inflammation of salivary glands) on lip biopsy.

Question 31

What is the risk for pregnant women with anti-SSA antibodies?

Answer 31

Pregnant women with anti-SSA antibodies are at risk of delivering babies with neonatal lupus and congenital heart block.

Question 32

What is the increased risk in Sjögren Syndrome?

Answer 32

Increased risk for B-cell (marginal zone) lymphoma, which presents as unilateral enlargement of the parotid gland late in the disease.

Question 33

What is Systemic Sclerosis (Scleroderma)?

Answer 33

An autoimmune disorder characterized by sclerosis of the skin and visceral organs, commonly affecting middle-aged females (ages 30-50 years)

Question 34

What causes the fibrosis seen in Systemic Sclerosis (Scleroderma)?

Answer 34

Fibroblast activation leads to collagen deposition. Endothelial dysfunction and secretion of growth factors (e.g., TGF-β and PDGF) cause fibrosis and organ damage.

Question 35

What is Limited Type systemic sclerosis (scleroderma)?

Answer 35

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.

Question 36

What is Diffuse Type systemic sclerosis (scleroderma)?

Answer 36

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).

Question 37

What is Mixed Connective Tissue Disease (MCTD)?

Answer 37

An autoimmune disease that shows mixed features of SLE, systemic sclerosis, and polymyositis.

Characterized by ANA and serum antibodies to U1 ribonucleoprotein.