[Frontiers in Bioscience E1, 577-586, June 1, 2009]

Rheumatoid arthritis is caused by Proteus : the molecular mimicry theory and Karl Popper

Alan Ebringer1, Tasha Rashid1

1Analytical Sciences Group, King's College, London, England


1. Abstract
2. Introduction
3. The search for the cause of RA
3.1. Popper's method of scientific investigation
3.2. Properties of the RA problem
3.2.1. RA and women
3.2.2. RA and onset in post-partum period
3.2.3. RA and smoking
3.2.4. RA in identical twins
3.2.5. The genetic factor in RA
3.3. Molecular mimicry as a model
3.3.1. Rheumatic fever
3.3.2. Ankylosing spondylitis
3.3.3. Immune response genes and TGAL
3.4. Molecular mimicry and Proteus
3.4.1. HLA-DR4 in rabbits
3.4.2. Antibodies to Proteus in RA
3.4.3. Molecular link between HLA-DR1/4 and Proteus haemolysin
3.4.4. Molecular link between Proteus urease and type XI collagen
3.4.5. Cytotoxic activity of RA sera
3.4.6. Comparison of molecular mimicry and receptor hypothesis models
4. Conclusion
5. References


Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the "shared epitope" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The "Popper sequences" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the "molecular mimicry" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the "shared epitope" and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.