Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response

Eur J Immunol. 1996 Oct;26(10):2480-6. doi: 10.1002/eji.1830261031.


We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus-transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history of Mycobacterium tuberculosis (TB) and four normal controls (NI). Fifty-eight RF were analyzed for specific activity (international units-RF/microgram) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain region of 16 (9TB-/7RA-) RF. Significant differences were observed between the NI-RF and the TB- and RA-RF. While the RF repertoire of normal individuals comprised of low-avidity RF of which the majority (15/17) were polyspecific, more than half of the TB- and RA-RF were monoreactive. Furthermore, the monospecific TB- and RA-RF were of significantly higher avidity than the NI-RF (RA > TB > > NI). With respect to polyspecificity specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3-0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V-D-J heavy chain regions showed significant differences between the respective RF. The salt-sensitive binding was highly correlated with the presence of arginine in the complementarity-determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ-line encoded antibodies, the genes of the monospecific RA/TB-RF were somatically mutated (RA > TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Anions
  • Antibody Specificity
  • Arthritis, Rheumatoid / immunology*
  • Base Sequence
  • Epitopes
  • Female
  • Genes, Immunoglobulin
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Rheumatoid Factor / genetics
  • Rheumatoid Factor / immunology*
  • Tuberculosis, Miliary / immunology*
  • Tuberculosis, Osteoarticular / immunology*


  • Anions
  • Epitopes
  • Rheumatoid Factor

Associated data

  • GENBANK/X99352
  • GENBANK/X99353
  • GENBANK/X99354
  • GENBANK/X99355
  • GENBANK/X99356
  • GENBANK/X99357
  • GENBANK/X99358
  • GENBANK/X99359
  • GENBANK/X99360
  • GENBANK/X99361
  • GENBANK/X99362
  • GENBANK/X99363
  • GENBANK/X99364
  • GENBANK/X99365
  • GENBANK/X99366
  • GENBANK/X99367