Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Analysis of SLAM Family Receptors in SLE
Kim1, Jong R., Patel1, Rahul K., Mathew1, Stephen O., Pertusi2, Raymond M., Mathew1, Porunelloor
The SLAM family receptors play a critical role in activation and regulation of immune function.SLAM family receptor genes are also located on chromosome region 1q23, a region linked in genetic studies of systemic lupus erythematosus. Here, we investigated the expression and alternative splicing of 2 SLAM family receptors, 2B4 and CS1, in patients with systemic lupus erythematosus.
45 patients with SLE and 30 healthy controls were studied. SLEDAI scores of SLE patients were calculated at the time of enrollment. Peripheral blood mononuclear cells (PBMC) were isolated and studied for 2B4 and CS1 expression on T, B, NK, and monocytes by flow cytometry. Total RNA was isolated from PBMC and reverse transcriptase PCR (RT-PCR) was performed for 2B4, CS1. Single-stranded conformational polymorphism (SSCP)-heteroduplex mobility shift assay (HMA) was conducted for analysis of 2B4 and CS1 polymorphisms.
Overall proportions of 2B4+ and CS1+ PBMCs were comparable in SLE and control subjects. However, frequency of 2B4+ cells was significantly decreased in CD56+ NK cells and CD14+ monocytes from patients with SLE compared to healthy controls (p<0.05). Also, increased CS1+ expression was noted in B cells of SLE patients vs. healthy controls. This increased CS1+ expression was associated with increased percentage of CD19 low B cells. The proportion of CS1 expressing cells in T cells, NK cells and monocytes was not significantly different between healthy controls and SLE patients. Two patients with SLE showed increased expression of h2B4-B splice variant over h2B4-A isoform, while 2 other SLE patients showed more predominance of h2B4-A over 2B4-B than healthy controls. However, there was no direct correlation between differential expression ratio of h2B4-A over h2B4-B and SLEDAI. Healthy individuals as well as most of SLE patients expressed similar or higher level of CS1-L isoform over CS1-S. However, the CS1-S isoform was overexpressed in 2 SLE patients.
These findings suggest a role for the differential expression of SLAM family receptors 2B4 and CS1 in systemic lupus erythematosus. In particular, we found decreased 2B4+ expression in NK cells and monocytes and increased CS1+ expression in B cells of SLE patients versus controls, as well as differential isoform expression in some SLE patients. Further functional studies and downstream signaling studies may be warranted to help confirm these findings and characterize their contribution to immune dysregulation in SLE.
To cite this abstract, please use the following information:
Kim, Jong R., Patel, Rahul K., Mathew, Stephen O., Pertusi, Raymond M., Mathew, Porunelloor; Analysis of SLAM Family Receptors in SLE [abstract]. Arthritis Rheum 2009;60 Suppl 10 :109