F.42. Altered RNA Editing in Ubiquitin Carboxyl-Terminal Hydrolase (UCTH) and Phosphodiesterase 8 (Pde8) Gene Transcripts of Systemic Lupus Erythematosus (SLE) T Lymphocytes

Abstracts tration, peripherally circulating CD19+ B-cell depletion occurred by Day 16 in all pts. The start of B-cell return was evident at 16 wks in some pts and coincided with a mean lowlevel serum RTX concentration of 7.5 Ag/mL. However, some pts remained peripherally depleted for the entire 48 wks. ACR20/50 score at Wk 24 was seen in 65%/33% of pts on RTX alone, 76%/41% of pts on RTX+CTX, and 73%/43% of pts on RTX+MTX. Differences in the pattern of peripheral B-cell return were not discernable between responders and nonresponders. In conclusion, RTX PK parameters are not affected by coadministration of CTX or MTX. Depletion of peripheral levels of the CD20+ B-cell subpopulation is not predictive of clinical response in RA pts; therefore, B-cell repletion should not be used in determining the timing of retreatment. doi:10.1016/j.clim.2006.04.080

F.41. IL-8 Levels in Cerebrospinal Fluid (CSF) Is a Useful Marker of Central Nervous System (CNS) Involvement in Systemic Lupus Erythematosus (SLE). Hilda Fragoso-Loyo, Yvonne Richaud-Patin, Alejando Orozco-Narvaez, Luis Davila, Luis Llorente, Jorge Sanchez-Guerrero. Department Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, D.F., Mexico. An accurate indicator of CNS involvement in SLE is yet to be found. Aim: To identify an indicator of CNS involvement in CSF of SLE patients. Patients and Methods: Forty-nine consecutive SLE patients with non-infectious CNS manifestations according to the ACR nomenclature, and who required hospitalization were identified. Patients were evaluated at the index hospitalization and six months later. At each of these evaluations, clinical status including lupus activity (SLEDAI) was assessed. CSF was obtained from 44 cases at baseline and 30 at 6 months. In addition, a CSF sample was obtained from 16 SLE patients without CNS manifestations and 27 patients with no autoimmune diseases during an elective surgical procedure, and from 7 SLE patients with septic meningitis. Soluble molecules were measured in CSF by cytometric bead array kits including cytokines (IL-2, IL-4, IL6, IL-10, TNF-alpha, IFN-gamma)and chemokines (MCP-1, RANTES, IL-8, MIG, IP-10). Results: From the whole range of molecules under study, MIG, IL-8, IL-6 and RANTES showed increased CSF values in patients with CNS involvement at the initial hospitalization compared with SLE patients without CNS manifestations (p b 0.05). Six months later, when CNS manifestations were in remission, the levels of MIG, IL-8 and IL-6 were comparable to those in SLE patients without CNS involvement. RANTES was the sole molecule that showed stable values between the two measurements. Cytokines and chemokines levels were higher in SLE patients with septic meningitis, with the exception of IL-8, which showed significantly higher values in SLE patients with CNS involvement (p = 0.01). Conclusion: Analysis of CSF IL-8 levels is the most useful indicator of CNS involvement in SLE. doi:10.1016/j.clim.2006.04.081

S65

F.42. Altered RNA Editing in Ubiquitin Carboxyl-Terminal Hydrolase (UCTH) and Phosphodiesterase 8 (PDE8) Gene Transcripts of Systemic Lupus Erythematosus (SLE) T Lymphocytes. Robert Orlowski, Kenneth O’Rourke, Dama Laxminarayana. Section on Rheumatology and Immunology/ Internal Medicine, Wake Forest University School of Medicine, Winston Salem, NC. The diverse immune dysfunctions in SLE are associated with abnormal expression of several gene products. RNA editing results in substitution of nucleotides and plays an important role in the regulation of gene expression. Altered expression of RNA editing genes was identified in SLE patients. UCTH is involved in degradation of proteins. PDEs play major role in the termination of cyclic nucleotide signaling and regulation of many cellular functions. Therefore, goal of these experiments is to identify RNA editing in UCTH and PDE gene transcripts of healthy controls and SLE patients. cDNAs synthesized from RNA extracted from normal and SLE T-cell samples were amplified by PCR using specific primer sets designed for the UCTH and PDE pre-mRNA. These transcripts were cloned into pCR2.1-TOPO vectors and analyzed for transcript editing. Sequence analysis of UCTH and PDE transcripts demonstrated A to I editing at known sites. Novel editing sites were also identified in UCTH and PDE gene transcripts of normal and SLE T-cells. Base 42424 was edited in about 60% of the analyzed PDE8 gene transcripts. This is the first identification of such extensive editing in non neuronal cells. In addition to these, novel editing sites and two hot spots for A to I editing were observed in the PDE gene transcripts. In general editing is impaired at known A to I editing sites in UCTH and PDE gene transcripts. Novel hot spot for A to I editing was identified between 39707 and 39527 bases in the UCTH gene transcripts of SLE T-cells. Based on these results, it is proposed that altered editing in SLE patients will attribute to the abnormal function of gene products and contribute for the immune dysfunctions in SLE. This work is supported by National Institutes of Health Grant AR48628 (to D.L.). doi:10.1016/j.clim.2006.04.082

F.43. Anti-TNFA Induced Apoptosis Contributes to the Induction of Autoantibodies but Not the Decrease of Synovial Inflammation in Spondyloarthropathy (SPA). Tineke Cantaert,1 Leen De Rycke,2 Bernard Vandooren,2 Elli Kruithof,2 Filip De Keyser,2 Eric Veys,2 Dominique Baeten.1 1 Division of Clinical Immunology and Rheumatology, Academic Medical Center/ University of Amsterdam, Amsterdam, Netherlands; 2Department of Rheumatology, Ghent University Hospital, Ghent, Belgium. Objective: Infliximab, but not etanercept, induces apoptosis of activated macrophages and T lymphocytes in vitro, but the in vivo relevance remains controversial. Therefore, we assessed the local and systemic induction of apoptosis and related this to modulation of synovial inflammation and