Molecular analysis of rheumatoid factors derived from rheumatoid synovium suggests an antigen-driven response in inflamed joints

Arthritis Rheum. 1993 Mar;36(3):380-8. doi: 10.1002/art.1780360314.

Abstract

Objective: Understanding the molecular genetic basis for rheumatoid factor (RF) production is necessary to a better understanding of the etiology and pathogenesis of rheumatoid arthritis (RA). We sought to define the genetic basis of RF in RA.

Methods: The heavy and light chain variable region genes encoding 4 human monoclonal RF were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide chain-termination method.

Results: The heavy and light chains of the C6 RF and the light chain of the G9 RF were encoded by 3 new RF-related Ig V-region genes. The heavy and light chains of D5 and G4 RFs were identical; most of their mutations caused amino acid substitutions.

Conclusions: The RF-related Ig V-region gene repertoire is large and is still expanding. The data from D5 and G4 strongly suggest that these 2 RFs arise in an antigen-driven response in rheumatoid synovium. The presumed germline V genes for C6 may represent disease-specific RF-related V genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / genetics
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Base Sequence
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / genetics
  • Male
  • Mice
  • Molecular Biology
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Rheumatoid Factor / genetics*
  • Synovial Fluid / immunology*

Substances

  • Antibodies, Monoclonal
  • Autoantigens
  • Immunoglobulin G
  • Oligonucleotide Probes
  • Rheumatoid Factor

Associated data

  • GENBANK/S56182
  • GENBANK/S56184
  • GENBANK/S56194
  • GENBANK/S56197
  • GENBANK/S56199
  • GENBANK/S56604
  • GENBANK/X62987
  • GENBANK/X62988
  • GENBANK/X62989
  • GENBANK/X62990