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.
CD138 RNA Can Be Detected in the Circulation of Patients with Systemic Lupus and Correlated to Other Factors Suggestive of Plasma Cell Activation.
Chen3, Ming, Hutcheson2, Joy G., Kamp2, Stan, Walker2, Danny, Merrill1, Joan T.
Plasma cells are key components in models of SLE pathogenesis, but are sequestered from easy analysis in humans, being rare and difficult to detect in peripheral blood. We hypothesized that quantification of CD138 RNA by real time PCR of peripheral blood leukocytes might provide a sensitive marker for activation of the plasma cell compartment.
The following measurements were performed on blood samples from 102 patients with SLE: CD138 RNA by RTPCR, BLyS (BAFF) RNA and protein by RTPCR and ELISA, and immune complexes (CIC/C1Q) by ELISA. Routine blood testing and clinical information were also recorded.
CD138 RNA was detectable in most patient samples. Samples were divided into two groups: Group A was comprised of 39 patients with higher levels of CD138 (528 copies/5ng). Group B included 61 patients with CD138 < 5 copies/5 ng. There were no differences in age (median 46 vs 47), gender (% female 89.5 vs 91.3) or ethnicity (% CAUC/AFR/ASIAN 63/26/11 Group A and 61/21/18 Group B). Compared to group B, Group A had greater prevalence of anti-dsDNA (28% vs 6.5%, p=0.008), and C3 below normal (25.6% vs 5.0%, p=0.007). Group A trended to higher levels of immune complexes (median 417 ng/ml vs 189, p=ns) as well as increased BLyS protein (median 3333 ng/ml vs 2805, p=ns) and BLys RNA (median 529 copies/5ng vs 421, p=ns). Levels of CD138 did not impact on disease activity by SLEDAI or BILAG, although CIC were increased in patients with SLEDAI >/= 6 vs those with lower scores (median 1580.7ng/ml vs 132.6, p=0.009) as were levels of BLyS protein (median 3927ng/ml vs 2742, p=0.042). An exploratory multivariate analysis was performed, considering the possibility that circulating CD138 reflects increased global plasma cell activity, which might contribute to autoantibody formation and complement consumption systemically. C3 levels were chosen as the dependent variable by virtue of being the furthest downstream of the elements studied. After adjusting for several potentially confounding factors, CD138 maintained a strong, independent effect on C3 levels (see table).
Variables With Potential Impact on Complement C3
|Independent Variables||Univariate p value||Multivariate p value|
CD138 can be measured in peripheral blood from lupus patients and may be related to meaningful upstream B Cell stimulants (such as BLyS) as well as downstream effects of plasma cell activation, including anti-dsDNA antibodies and complement consumption. Since some biologic agents in development are expected to have more impact on plasma cells than others, studies of the few that enter the circulation could provide predictive biomarkers for treatment selection.
To cite this abstract, please use the following information:
Chen, Ming, Hutcheson, Joy G., Kamp, Stan, Walker, Danny, Merrill, Joan T.; CD138 RNA Can Be Detected in the Circulation of Patients with Systemic Lupus and Correlated to Other Factors Suggestive of Plasma Cell Activation. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1186