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A8.34 CD1C + dendritic cells are overrepresented in lymph nodes of early arthritis patients and related to B cell responses
  1. T H Ramwadhdoebe1,2,
  2. L G M van Baarsen1,2,
  3. F H Berger3,
  4. M Maas3,
  5. D M Gerlag1#,
  6. P P Tak*,1,
  7. M C Lebre1,2
  1. 1Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  2. 2Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  3. 3Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  4. *Currently also: University of Cambridge, Cambridge, UK and GlaxoSmithKline, Stevenage, UK
  5. #Currently also GSK, Clinical Unit Cambridge, R&D Projects Clinical Platforms & Sciences, Cambridge, UK

Abstract

Background and Objectives The immune system is composed of different cell populations that circulate in our body through lymphoid organs. We have recently shown that the numbers of CD69+ T cells and B cells are increased in lymph node (LN) biopsies from early arthritis patients. DCs are fundamental in initiating and modulating T and B cell responses and may therefore play an essential pathologic role in autoimmune diseases. We hypothesize that an in-depth analysis of DCs within LNs of at risk individuals and early arthritis patients can provide a better understanding of immune function and dysregulation during the earliest phases of arthritis.

Materials and Methods We included 22 individuals with arthralgia without any evidence of arthritis who were positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies (ACPA; RA risk group), 20 DMARD and biological naïve early arthritis patients (2010 criteria < 1 year) and 8 seronegative control individuals. All study subjects underwent ultrasound-guided inguinal LN biopsy. DC subsets (CD1a, CD1c, and CD304) were analysed by multi-colour flow cytometry.

Results All DC subsets included in this study could be detected in LN biopsies. However, CD1c+ DC were the major subset present in LNs of early arthritis patients compared to both CD304+ DCs (p < 0.0001) or CD1a+ DCs (p < 0.002). In line with this, there was a significant increase of CD1c+ DCs in the early arthritis group compared to the at risk group (p = 0.009) and compared to control individuals (p = 0.01). Moreover, in early arthritis patients the frequencies of CD1c+ DCs were significantly increased in ACPA+ compared to ACPA- patients (p = 0.03). The frequencies of CD304+ DC were also significantly increased in early arthritis compared to the at risk group (p = 0.009) but did not correlate with ACPA status.

Conclusions This is the first study that reports the presence of DC subsets in LNs during the earliest phases of arthritis. As CD1c+ DCs are the main DC subset present in early arthritis and the only subset related with ACPA status, this study supports the notion that in addition to the well-known capacity of CD1c+ DCs to activate naïve T cells, CD1c+ DC might also contribute to B cell responses.

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