Overview of Autoimmunity and Emerging Therapies
Christopher Bowlus, MD, UC Davis
What is Autoimmunity?
- Normal immune function
- Self versus non-self
- Tolerance
- Disease specify autoimmunity
- Pancreas - Juvenile Diabetes
- Brain - Multiple Sclerosis
- Joints - Rheumatoid Arthritis
What causes Autoimmunity?
- Genes and Environment
- Lymphocytes
- Immune cells that respond to infections
- B cells produce antibodies; e.g. Anti-mitochondrial antibody
- T cells produce cytokines (producing effects of illness, such as fever) to kill infected cells; e.g. TNF-alpha seen in RA and Crohn's Disease
What causes Liver Autoimmunity?
- Autoimmune hepatitis (AIH)
- Hepatocyte (main liver cell)
- PBC
- PSC
- Medium and large bile ducts
- 20% of PBC and PSC patients have overlap with AIH
Old Therapies
Treating the effects of disease without treating the underlying cause
- URSO - PBC, PSC
- Methotrexate - undesireable side effects
- Prednisone - undesireable side effects
- Imuran - undesireable side effects
Newer Drugs/Novel Approaches
Attempting to treat the underlying cause
- Anti-TNF (Remicade)
- Effective in Crohn's Disease, Rheumatoid Arthritis
- Anti-B cell (Rituxan)
- Used for lymphoma
- Effective in Rheumatoid arthritis
- Study starting for PBC (Dr. M.E. Gershwin) at UC Davis
- Anti-cytokine
Future Studies
- High Dose Immunotherapy
- Stem cell transplantation
Obstacles to Clinical Studies in Autoimmune Liver Diseases
- Rare diseases
- Small market compared to IBD, RA, MS; not attractive to pharmaceutical companies
- Lack of understanding of disease
- Difficult to assess effects
- Slow progression of disease
- Lack of non-invasive tools to measure effects
Rituxan Study for PBC
Study is limited to 10 patients
- Women 18-65 years old
- Elevated Alkaline Phosphatase despite treatment with ursodeoxycholic acid (URSO, Actigall)
- Stage I, II or III PBC on biopsy
- Contact: Chris Aoki, M.D.
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