Rheumatoid arthritis--a gene transfer disease

Area of Science:

• Immunogenetics
• Rheumatology
• Molecular Biology

Background:

• Rheumatoid arthritis (RA) patient sera were crucial for identifying human immunoglobulin (Ig) allotypes in the Gm system.
• RA patients exhibit a propensity for immune responses against human Ig allotypes, challenging established immunological principles.
• Previous studies defined major Gm allotypes using amino acid, nucleotide, and gene technology.

Purpose of the Study:

• To investigate paradoxical findings regarding Gm allotypes and anti-Gm responses in RA.
• To re-evaluate the etiology of RA, considering a gene transfer hypothesis.
• To explore the role of viral gene transfer, particularly herpesviruses, in RA pathogenesis.

Main Methods:

• Analysis of Gm allotypes and anti-Gm antibodies in RA patient sera.
• Application of gene technology for allotype definition.
• Review of viral mechanisms for gene transfer and expression in RA synovial tissue.

Main Results:

• Observed non-nominal or hidden allotypes, seemingly contradicting Mendelian inheritance.
• Confirmed prevalent immune responses to allotypes from other individuals in RA patients.
• Demonstrated expression of transferred incompatible Ig allotype genes in RA synovia.

Conclusions:

• RA may originate from gene transfer rather than being a primary autoimmune disease.
• Viral gene transfer, potentially by herpesviruses, could introduce incompatible Ig allotypes.
• Formation of Ig-anti-Ig complexes from transferred genes may contribute to RA's arthritogenic potential.