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AB0088 Transgenic ZAP-70+ B Cells Mice Show A More Severe Collagen Antibody Induced Arthritis (CAIA) than Wild Type
  1. F. Biscetti1,
  2. F. Angelini2,
  3. S. Gobessi3,
  4. E. Gremese1,
  5. B. Tolusso1,
  6. D. Efremov3,
  7. G. Ferraccioli1
  1. 1Rheumatology
  2. 2Internal Medicine, Catholic University School of Medicine
  3. 3International Centre for Genetic Engineering and Biotechnology, Rome, Italy

Abstract

Background Zeta-chain-associated protein kinase 70 (ZAP-70), a tyrosine kinase constitutively expressed in T cells, can be found in B cells and is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia. We previously provided evidence that a subset of B cells in patients with rheumatoid arthritis (RA) expresses ZAP-70, that marks the memory B cell subsets (IgD+CD27+ and IgD-CD27+), thus suggesting that the ZAP-70+ B cells represent a memory activated subset likely involved in the maintenance of an activated B cell pool [1–3].

Objectives The aim of the present study was to clarify whether B cells, especially ZAP-70 expressing B cells, represent indeed a risk for a severe expression of arthritis in a transgenic ZAP-70+B murine model.

Methods Male transgenic ZAP-70+B mice, that has already been shown to present an high ZAP-70 expression in the B cell lineage [4], aged 8–12 weeks old were used for experiments. All the animals were injected with a cocktail of 5 monoclonal antibodies recognizing the conserved epitopes on various species of type II collagen. Three days later the mice were injected with LPS from E. coli 0111:B4 to trigger arthritis development. Animals were evaluated every 3 days after the infusion of the antibody cocktail for arthritis incidence and each paw was evaluated and scored individually on a scale of 0–4. An arthritis index (AI) that expressed a cumulative score for all paws was calculated for each animal.

Results We found that the transgenic ZAP-70+B cells mice presented a more severe form of arthritis, compared to wild type age-matched mice (p<0.001) (Figure). Histological and immunohistochemical analyses confirmed the presence of joint erosions and inflammatory infiltrate at the level of the synovium of ZAP-70+B cells mice.

Conclusions These data suggest that B cells amplify the degree of CAIA, that ZAP-70 is involved in the pathogenesis of arthritis in an RA-like model, and that this tyrosine kinase likely represents a possible target of therapy.

  1. Tolusso B, et al. Clin Immunol. 2009 Apr;131(1):98–108

  2. Michelutti A, et al. Mol Med. 2011 Sep-Oct;17(9–10):901–9

  3. Gremese E, et al. J Rheumatol. 2012 Dec;39(12):2276–85

  4. Gobessi S, et al. Blood (ASH Annual Meeting Abstracts) 2011 118: Abstract 2830?

Disclosure of Interest None declared

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