CIDPUSA.ORG

• Danger/damage theory: tissue destruction, activation of macrophages, and a co-stimulatory second signal causing AI.
• Inflammation areas: Another possibility is that simply the fact that a site of the body gets infected could perhaps lead to an autoimmune response against that site.
• Superantigens: Most superantigens for humans are found in bacteria, but bacterial infections are not strongly associated with AI diseases. However, there are some possible examples of links: Kawasaki syndrome of childhood multi-system vasculitis, guttate psoriasis.
• Balance theory: Antigen injections can cause AI by over-balancing. Paraneoplastic syndromes expose too much of an already exposed antigen (in a new site). Same as the danger theory? Rare antigens like GAD in islet cells (only pancreas and brain)

Evidence about various theories:

• Thymus or bone marrow problems don't cause autoimmunity: The thymus and bone marrow are the places where much of the tolerance occurs according to negative selection theories. The fact that thymus abnormalities only cause rare autoimmune diseases, rather than commonly, would seem to indicate that failure of thymic selection of T-cells has only a minor causal effect on autoimmunity. A few rare AI diseases do result from thymomas and lymphomas (bone marrow disorders). This indicates that peripheral tolerance may be more important.

Autoimmunity:

The predominant theory about autoimmune diseases is that they are autoimmune. Though facetiously stated, it is important to remember that autoimmunity itself is only a theory, and in fact a relatively recent theory from the last few decades. It has taken a long time for the many disparate diseases of different body organs to be brought into a single disease class.

Strictly speaking, there could be other possible theories of autoimmune diseases. If we assume that the disease involves cell death (another assumption), then a list might look something like:

• Theory 1: Autoimmunity: immune system kills the cells
• Theory 2: Apoptosis error: cells commit suicide for some aberrant reason, and the immune system is only there to clean up afterwards.
• Theory 3: External cell damage: some virus, bacteria, toxin, or event kills the cells, and the immune system cleans up.

Treatment of Autoimmune Diseases

• Anti-inflammatory: steroids, NSAIDs ( Asprin).
• Immune Modulation (IVIg)
• Immune suppression
• Oral tolerizations: mucosal immunotherapy, e.g. eating Myelin Basic Protein (MBP) might prevent MS; eating collagen might prevent RA. Better tolerization if use cholera toxin B as an adjuvant to the eaten antigen, actually to heighten the immune response and somehow thereby cause tolerance.
• Monoclonal antibodies , Rituxmab , Remicade
• Competitive ligands for T-cell receptors
• Cytokines
• Cytokine antagonists
  • Anti-TNF treats RA
• Chemokine receptor interference
• Free radical damage avoidance: nicotinamine and islet cells.
• Genetically altered T-cells
• Genetically altered cells to express regulatory anti-AI cytokines
• Finally antibiotics as used by CIDPUSA
•