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THU0020 Role of fcgammarii and fcgammariii in inflammation and cartilage damage during murine experimental antigen-induced arthritis
  1. PL Van Lent1,
  2. KC Nabbe1,
  3. AB Blom1,
  4. AE Holthuysen1,
  5. LB Van de Putte1,
  6. S Verbeek2,
  7. WB Van den Berg1
  1. 1Rheumatology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  2. 2Human and Clinical Genetics, University Medical Centre Leiden, Leiden, The Netherlands

Abstract

Background IgG-containing immune complexes, which are found in most RA joints, communicate with haematopoietic cells using three classes of Fc receptors (FcγRI, II, III). In a previous study we found that if an experimental arthritis was elicited in knee joints of FcR γ-chain deficient mice which lack functional FcγRI and III, joint inflammation was lower and severe cartilage destruction was absent.

Objectives To examine the role of FcγRII and III in inflammation and functional cartilage damage in knee joints with chronic experimental antigen-induced arthritis (AIA) using FcγRIII and FcγRII deficient mice.

Methods FcγRII and FcγRIII -/- mice and their controls were immunised with methylated BSA in complete adjuvant followed by induction of arthritis by local injection of mBSA into the right knee joint. The course of inflammation was studied by 99mTc uptake. Chronic inflammation and cartilage damage (depletion of proteoglycans, chondrocyte death and matrix erosion) was studied histologically in total knee joints sections stained with haematoxylin or safranin-O. Aggrecan breakdown in cartilage caused by metalloproteinases (MMP) was studied by immunolocalisation (VDIPEN neoepitopes) and image analysis.

Results Three weeks after immunisation both humoral (total IgG, IgG1, IgG2a and IgG2b levels) and cellular (T cell responses as measured by lymphocyte proliferation) immunity raised against mBSA was comparable in all groups examined. IgG2a levels were comparable in FcγRIII-/- but higher in FcγRII-/- if compared to controls. Joint swelling at day 1, 3 and 7 was similar in FcγRIII -/- mice and significantly (103%) higher in FcγRII-/- on day 1 but not on later time-points. Histologically, at day 7 after AIA induction, exudate and infiltrate in the knee joint was similar in FcγRIII -/- and significantly higher (100% and 388%) in FcγRII-/- mice if compared to controls. MMP-induced neoepitopes determined in various cartilage layers (tibia and femur) were comparable in FcγRIII-/- and higher (respectively 155–360% and 67–75%) in FcγRII-/-. Initial depletion of proteoglycans was similar (40–70%) in all groups. In the chronic phase, chondrocyte and cartilage matrix erosion in tibia and femur stage was significantly elevated in FcγRII -/- but not in FcγRIII-/- mice.

Conclusion FcγRIII is redundant or not involved in the presence of FcγRI whereas FcγRII is a crucial inhibiting factor in acute and chronic inflammation and cartilage erosion during antigen-induced arthritis.

Reference

  1. Van Lent, et al. Arthritis Rheum. 2000;43(4):740–52

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