Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Comprehensive Flow Cytometric Profiling of Peripheral Blood Dendritic Cells in Rheumatoid and Psoriatic Arthritis Patients.

Kobie6,  James, Panepento6,  Ben, Wang6,  Jyh-Chiang E., Chiu6,  Grace, Tabechian8,  Darren, Anandarajah2,  Allen P., Looney3,  Richard J.

University of Rochester, Rochester, NY
Univ of Rochester Med Ctr, Rochester, NY
University of Rochester, Rochester, NY
University of Rochester, Rochester, NY
University of Rochester, Rochester, NY
University of Rochester
University of Rochester Medical Center, Rochester, NY
University of Rochester School of Medicine, Rochester, NY

Purpose:

Dendritic cells (DC) are pivotal cells in the initiation of adequate immune responses. Peripheral blood dendritic cells (PBDC) have pleiotropic effects on T and B lymphocytes, however, their phenotypic and functional properties in rheumatoid (RA) and psoriatic arthritis (PsA) and vaccine responses are not well understood. Therefore, we performed a comprehensive examination of the PBDC profile of RA and PsA patients.

Methods:

Peripheral blood was collected longitudinally from a cohort of approximately 150 arthritis patients including, recently diagnosed RA (n=33), RA treated with methotrexate (MTX) (n=70), RA treated with TNF inhibitors (TNFi) (n=61), and PsA patients treated with anti-TNF (n=25). Samples from healthy control (HC) subjects (n=97) were also obtained. Peripheral blood was examined by an 11-color flow cytometry assay to identify, phenotype and assess endocytic ability of PBDC subsets. Subset analysis included resolution of previously characterized myeloid dendritic cell 1 (MDC1: CD11c+CD1c+), myeloid dendritic cell 2 (MDC2: CD11c+CD141+), and plasmacytoid (PDC: CD303+CD141-) populations in addition to several putative, poorly characterized PBDC subsets. A systems biology approach was utilized to assess differences in individual PBDC subsets and also differences in the overall composite PBDC profile.

Results:

Examination of myeloid DC subsets did not reveal any significant differences in the frequency or endocytic ability of MDC1 among study groupsRecently diagnosed RA patients exhibited a consistent decrease in the frequency of MDC2 as compared to HC that reached significance at one time point. No consistent differences in the frequency of PDC was observed among study groups, although a trend toward decreased PDC in RA patients treated with MTX as compared to HC was observed. Principal components analysis of composite PBDC profiles revealed consistent significant differences in the PBDC profile of RA patients treated with MTX at multiple time points as compared to HC, that were largely influenced by relative changes in the frequency of PDC and a putative PDC-like subset. A significant decrease in MDC1, independent of study group was observed shortly after seasonal influenza vaccination.

Conclusions:

Although variations were observed in the frequency of PBDC subsets in arthritis patients, no substantial dysregulation was observed that was specific to RA or PsA patients or treatment with methotrexate or anti-TNF. Subtle changes in the overall PBDC profile were observed in RA patients treated with MTX that warrant further examination and may reflect alteration in PBDC development. Decreases in MDC1 after influenza vaccination, likely reflecting altered trafficking, highlight the dynamic nature of the PBDC profile and may represent a surrogate marker of vaccine response. These data also demonstrate that anti-TNF therapy does not significantly impact the circulating frequency or ratios of PBDC.

To cite this abstract, please use the following information:
Kobie, James, Panepento, Ben, Wang, Jyh-Chiang E., Chiu, Grace, Tabechian, Darren, Anandarajah, Allen P., et al; Comprehensive Flow Cytometric Profiling of Peripheral Blood Dendritic Cells in Rheumatoid and Psoriatic Arthritis Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :849
DOI: 10.1002/art.28617

Abstract Supplement

Meeting Menu

2010 ACR/ARHP