What is the definition of autoimmunity?
An immune reaction against self-antigens secondary to a loss of self-tolerance
- Can be isolated single organ disease or multi-organ systemic dysfunction
What are the possible mechanisms of injury for autoimmunity?
- *B-cells - Autoantibodies**:
- Ab dependent cellular cytoxicity (Type II)
- Complement (Type II)
- Anti-receptor antibody (Type II)
- Immune complexes (Type III)
- *Cell-mediated (type IV)**
- T cells and macrophages
How is self-tolerance prevented in the immune system?
- Clonal Deletion: Receptors strongly bind to self antigen, these cells are killed early on
- Clonal anergy: If, in periphery, there are self-reactive lymphocytes, they are made anergic
- Suppression: Tregulatory cells (CD3+CD4+CD25+FOXP3)
What is Systemic Lupus Erythematosus?
- Multisystem autoimmune disease of Connective Tissue Disorder (CTD) type
- CD4+ Tcell dependent B Cell hyperactivity
- Cell type-specific autoantibodies (type II) and immune complexes (type III) induce tissue injury
- interplay of multiple genes, hormones, and environmental influences
What are the Lupus Classification Criteria?
RASH ON MAIDS
- *R**enal
- *A**rthritis
- *S**erositis
- *H**ematologic (hemolytic anemia, leukopenia, thrombocytopenia)
- *O**ral ulcers
- *N**eurologic (psychosis, seizures)
- *M**alar rash
- *A**NA+
- *I**mmunologic (anti-dsDNA Ab, anti-Sm Ab, anti-phospholipid Ab)
- *D**iscoid rash
- *S**un sensitivity
What are the seronegative arthritises?
Ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
IBD-associated arthritis
What are environmental triggers of SLE?
UV light
Infection
Emotional stress
Surgery
Pregnancy, post-partum, and abortion
What is the immunologic pathophysiology for SLE?
Humoral Immunity:
- B cell hyperactiity and hypergammaglobulinemia
- Auto Abs
(ANA - Immune complexes)
(Antibodies to phospholipid-bound proteins)
(Antibodies to membrane proteins of specific cell types - hematologic and neuronal cell injury)
- Complement activation and decrease in serum complement (consumption)
- Cell-Mediated Immunity*:
- *- Excessive or poorly controlled CD4+ Th cell activity**
- Viruses implicated as triggers in genetically susceptible hosts
What specific anti-nuclear antibodies are present in SLE?
Anti-dsDNA and anti-Sm –> virtually diagnostic
Anti-histone (drug induced SLE)
Anti-SS-A [Ro] and Anti-SS-B [La] - subacute cutaneous lupus and congenital heart block (also Abs present in majority of Sjogren’s syndrome patients)
Anti-phospholipid Antibodies
What is the significance of anti-phospholipid antibody presence?
May lead to Antiphospholipid Syndrome:
Autoimmune hypercoagulable state caused by:
Anti-phospholipid-ß2 glycoprotein
Anti-cardiolipin (also causes false + syphilis)
Lupus anticoagulant (may show false + PPT elongation)
May lead to:
Venous and arterial thromboses
Spontaneous miscarriage
Focal cerebral ischemia
Ocular ischemia
What are the most characteristic SLE lesions secondary to immune complexes?
Skin (rash)
Kidneys (glomerulonephritis)
Blood vessels
Connective Tissue
What are the histological features of skin involvement in SLE?
Ig/complement complexes at dermal-epidermal junction
- lymphocytic infiltration at DEJ
- Liquefaction of basal layer of epidermis
- Edema and perivascular lymphocytes in dermis
Complex deposition made visible by “Lupus band test”
–> immunofluorescence of complex deposition
What skin involvement is seen in SLE?
- Erythema: Butterfly rash; similar rash on extremities and trunk
- Accentuation by sunlight
- Ulcerations (oral, vaginal, nasal)
- Alopecia
- Raynaud’s (arterial vasospasm in digits of hands and feet in response to cold or emotional stress)
- Vasculitis (majority-cutaneous and small vessel involvement)
What is subacute cutaneous lupus erythematosus?
- Multiple skin lesions with reddened raised borders, cenntral clearing, and light scale
- Present in sun-exposed areas (but not on face)
- Most patients have mild SLE symptoms
- Association with Anti-SS-A and Anti-SS-B, and HL-DR3 genotype
What is chronic discoid Lupus Erythematosus?
- Discoid rash present on face and scalp (occassionaly wide dissemination)
- Thick scales, atrophy, scarring, edema, erythema
- Only 5-10% develop multisystem features of SLE after many years
- 35% ANA+ (anti-dsDNA rare)
What renal involvement is seen in SLE?
Lupus Nephritis
- Immune complex-mediated
- High titers anti-dsDNA associated with active renal disease
- Glomerular tubulointerstitial, and vascular involvement
- Proteinuria and hematuria in Urinalysis
- Serum creatinine increased with renal insufficiency
- Important source of morbidity and mortality
What musculoskelatal involvement is seen in SLE?
- *Arthralgias and/or Arthritis**
- Small joints
- Symmetric
- Non-erosive synovitis
- Swelling and pain
- *Myopathy**
- Muscle pain and weakness
What neuropsychiatric involvment is seen in SLE?
- *Neurologic**
- headache
- SEIZURES
- cranial/peripheral neuropathy
- stroke
- chorea
- retinopathy (vasculitis)
- *Psychiatric**
- PSYCHOSIS
- Depression
- Organic brain syndrome
Anti-phospholipid Ab-mediated damage of endothelium (occulsion of small vessels)
Antibodies against synaptic membrane protein
What are the most common causes of death in SLE?
- renal failure
- intercurrent infections
- coronary artery disease (atherosclerosis)
What are characteristics of Drug induced lupus?
Fever, arthritis, and serositis (Pleuritis, pericarditis)
–> NO renal or CNS involvment
- ANA+, but no anti-dsDNA –> anti-histone instead
- Normal serum complement
–> STOP DRUG, disease resolves
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Review of Systems18
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Antibiotics71
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Microbiology121
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Immunology31
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Antibiotics71
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Pathology: Autoimmune Disorders15
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Hypersensitivity Reactions11
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Pharmacology: Hypersensitivity14
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SLE20
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Immunomodulatory Drugs35
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RA and Systemic Sclerosis23
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Primary Immune Disorders19
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Cystic Fibrosis46
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HIV Virology11
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Antiviral Drugs33
