Gender Differences in Immune Response

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Gender Differences in Immune Response

• Females resist a variety of infections better
  than males ???
• Females may reject transplanted organs more
  rapidly
• Females have a higher frequency of autoimmune
  diseases

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Evidence to Support Hormone Role in Human Lupus

• Female predominance
• Disease ? during pregnancy, menses
• ? Levels of androgen in women with lupus
• ? Frequency of lupus in Klinefelter (XXY) men
• ? Disease with estrogen administration ?

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Evidence to Support Hormone Role in Murine Lupus
Mouse model lupus (NZB x NZW) disease identical
to human F gt M
Female mice die earlier than males
Male castration and estrogen accelerates
disease
Male sex hormones delay onset of lupus in
female mice
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Role of Hormones on Immune Function

• Male hormones (androgen) suppress
• Female hormones (estrogen) enhance

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CRITERIA FOR THE DIAGNOSIS OF SLE (As revised in
1997 by the American College of Rheumatology)

• A person is said to have SLE if four of these
  criteria are present at any time
• Skin criteria
• Butterfly rash (lupus rash over the cheeks and
  nose)
• Discoid rash (thick rash that scars, usually on
  sun-exposed areas
• Sun sensitivity
• Oral ulcerations
• Systemic criteria
• Arthritis
• Serositis
• Proteinuria or cellular urinary casts
• Seizures or psychosis with no other explanation

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Diagnostic Challenges

• Con
• 1. Interpretation of criteria
• 2. Manifestations not in criteria
• 3. Other diseases may mimick lupus
• 4. Evolving symptoms over time
• 5. Patients may present very differently

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Disease Mimickers

• Sjogrens syndrome
• Fibromyalgia ( ANA)
• Early rheumatoid arthritis
• ITP
• Primary antiphospholipid syndrome
• Drug-induced lupus

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Natural History of SLE

• Disease flares/activity (reversible)
• Organ damage (irreversible)
• disease
• treatment

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SLE Damage
SLE Activity
1 2 3 4 5 6 7 8
Time (years)
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SLE Activity vs Damage

• Damage
• Renal failure/scar
• Osteoporosis/Fx
• Ovarian failure
• Myocardial infarction

• Activity
• Nephritis
• Inflammation and
• medications

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Autoantibody Determined Clinical Subsets of SLE
phospholipids
Ribosomal-P
ANA ()gt95 patients
ANA gt 90, nonspecific
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CD40L-CD40 Interactions
TCR
T-cell
B Cell
CD3
CD40
CD40L (gp39)
CD40 B-cells, endothelial cells, macrophages,
Ag-presenting cells, renal parenchymal, tubular,
etc cells
CD40L T-cells, platelets
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Autoantibody Determined Clinical Subsets of SLE
RNP (Raynauds)
Phospholipid (clotting and miscarriage)
Ribosomal-P (CNS, psychosis)
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Pathogenesis of SLE
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Current Standard Therapy
Mild to Moderate Disease Therapy
arthritis photoprotection fever NSAID pl
eurisy corticosteroids pericarditis metho
trexate cutaneous antimalarials topica
l agents physical therapy
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Current Standard Therapy
Moderate to Severe Disease Therapy
nephritis corticosteroids vasculitis cyclo
phosphamide pneumonitis azathioprine CNS
cyclosporine hematologic IVIg plas
mapheresis ??? mycophenylate mofetil
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Novel Therapies
Immunosuppressants T cells B cells Complement
Cytokine Hormonal Immunoablation
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Lupus Center of Excellence 2004
Lupus Center of Excellence 2003