Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Perturbations in B-Cell Homeostasis in Primary Sjgrens Syndrome
Roberts1, Mustimbo, Wei2, Chungwen, Roger3, James, Sanz4, Iñaki, Anolik1, Jennifer H.
University of Rochester, Rochester, NY
University of Rochester
University of Rochester School of Medicine and Dentistry, Rochester, NY
University of Rochester School of Medicine and Dentistry, Rochester, NY
Purpose:
To elucidate abnormalities in B cell homeostasis with pathophysiological and diagnostic implications for primary Sjogren's Syndrome (pSS). Multicolor flow cytometry was used in a cross-sectional analysis of patients that meet AECG criteria for the diagnosis of pSS as compared to patient with a clinical diagnosis of pSS and patients with sicca symptoms referred to our Rheumatology clinics for the evaluation of possible pSS. We also initiated longitudinal analysis to identify biomarker candidates that could be then validated for their predictive value for the development of full-blown pSS.
Method:
B-cells from pSS (n=17), SLE (n=26), RA (n=26), healthy controls (n=24) and longitudinal pSS (n=11) patients were analyzed by multicolor flow cytometry for expression of CD24, CD27, CD38, IgD, B220, CXCR3 and CXCR5 in C19+ B cells.
Results:
As reported by others, pSS patients feature decreased frequencies of switched memory (SM) (IgD-/CD27+) and unswitched memory (UM) (IgD+/CD27+) cells as compared to healthy controls (HC) (p=0.0007, p=<0.0001). In contrast CD27-/IgD- switched cells, a population we reported expanded in SLE, were significantly increased in pSS (p=0.0142). We also report that similar to SLE, there is a significant decrease of UM cells in pSS but not RA. Our use of multicolor flow cytometry revealed a relative expansion within the IgD-, CD27+ and CD27-, population of a novel B220+/CXCR3+/CXCR5- subset with a phenotype suggestive of effector B cells. Our preliminary data also indicate that the reported expansion of pre-GC cells (Bm2') may be explained partly by increased transitional B cells (CD24hi/CD38hi). Finally, longitudinal analyses indicate that a decrease in the frequency of UM cells may constitute a valuable indicator of clinical progression to pSS.
Conclusion:
Our data provide greater understanding of B-cell homeostasis in pSS and identify more discreet memory subsets that might be implicated in the pathogenesis of the disease and serve as biomarkers for diagnosis and disease progression. The decrease in UM B-cells appears to be the earliest change in the progression to pSS and may bear substantial pathophysiological significance as equivalent marginal zone-like cells have been postulated to play protective roles against autoimmunity in animal models. The CXCR3+/CXCR5-/B220+ population of B-cells is hypothesized to represent effector B cells with enhanced ability to migrate to inflamed target tissues and contribute to disease. Our data suggest a model of clinical autoimmunity onset triggered by an imbalance of regulatory/effector B cell functions mediated by a decrease in regulatory B-cells which may represent an early biomarker in the development of pSS. The presented results also identify the expansion of new candidate effector B cells.
To cite this abstract, please use the following information:
Roberts, Mustimbo, Wei, Chungwen, Roger, James, Sanz, Iñaki, Anolik, Jennifer H.; Perturbations in B-Cell Homeostasis in Primary Sjgrens Syndrome [abstract]. Arthritis Rheum 2009;60 Suppl 10 :498
DOI: 10.1002/art.25580
