title: Responses of lymphocytes of patients with rheumatoid arthritis to IgG modified by oxygen radicals or peroxynitrite.
abstract: OBJECTIVE
  We have previously demonstrated the presence of IgG aggregates modified by oxygen radicals (chlorinated IgG [Cl-IgG]) and peroxynitrite (nitrated IgG [N-IgG]) in synovial fluid of patients with rheumatoid arthritis (RA). A possible explanation for the longstanding chronic inflammatory process in RA is the establishment of an immune response to autoantigens. This study was undertaken to examine whether a T cell response to oxidatively modified IgG contributes to the inflammation in RA.
  
  
  METHODS
  We studied in vitro lymphocyte proliferation and interleukin 2 (IL-2) secretion in response to a common antigen (mumps), N-IgG, Cl-IgG, and heat-aggregated IgG (H-IgG) (control) in 15 normal blood donors and 16 RA patients not receiving immunosuppressive drugs.
  
  
  RESULTS
  The responses of RA lymphocytes to mumps antigen were significantly lower that those in controls (mean +/- SEM 2,577 +/- 217 versus 6,367 +/- 365 counts per minute/well; P < 0.02). However, whereas in normal donors the cell responses to N-IgG and Cl-IgG were not significantly different than responses to H-IgG (N-IgG/H-IgG ratio 1.2 +/- 0.2, Cl-IgG/H-IgG 1.5 +/- 0.2), the RA lymphocyte responses to N-IgG and Cl-IgG were significantly higher than the responses to H-IgG (N-IgG/H-IgG 7.4 +/- 2.5, Cl-IgG/H-IgG 4.8 +/- 1.2). When ratios in RA cells were compared with normal cell responses as a group, there was a significant difference for both N-IgG (P < 0.017) and Cl-IgG (P < 0.014). When selected normal and RA lymphocyte culture supernatants were assayed for IL-2 secretion, the increase in IL-2 never exceeded 2-fold in normal cell cultures incubated with any of the IgG compared with unstimulated cultures, whereas responses of RA cells, particularly those incubated with N-IgG, were increased (range 2.6-15.7-fold) compared with unstimulated controls.
  
  
  CONCLUSIONS
  These results suggest that in RA there are circulating T cells that are responsive to oxidatively modified IgG, a possible pathogenic mechanism contributing to the chronic inflammatory process within the inflamed joint.
authors.affiliation: Division of Rheumatology, UAMS #509, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Grinnell
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hugo E
authors.initials: HE
authors.lastname: Jasin
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000187:drug effects* / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009109:Mumps virus / Q000276:immunology; D016877:Oxidants / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology
chemical_list: D000956:Antigens, Viral; D007074:Immunoglobulin G; D007376:Interleukin-2; D016877:Oxidants; D010835:Phytohemagglutinins; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid