As for the complete populations, ideals for SLE were significantly higher than those for possibly RA or normal settings (P 0.004; data not really shown). == Correlations between BLyS guidelines and plasma immunoglobulin amounts == BLyS is a potent B cell success factor [15-21], and administration of exogenous BLyS to mice qualified prospects to B cell hypergammaglobulinemia and enlargement [1]. connected with serum immunoglobulin amounts and SLE Disease Activity Index ratings than had been BLyS proteins amounts. Furthermore, adjustments in SLE Disease Activity Index ratings were more carefully associated with changes Raphin1 acetate in BLyS mRNA levels than with changes in BLyS protein levels among the 37 SLE patients from whom repeat blood samples were obtained. Thus, full-length BLyS and BLyS mRNA levels are elevated in SLE and are more closely associated with disease activity than are BLyS protein levels. BLyS mRNA levels may be a helpful biomarker in the clinical monitoring of SLE patients. == Introduction == B lymphocyte stimulator (BLyS; a trademark of Human Genome Sciences, Inc., Rockville, MD, USA) is a 285-amino-acid member of the tumor necrosis factor ligand superfamily [1-3]. A causal relation between constitutive overproduction of BLyS and development of systemic lupus erythematosus (SLE)-like illness has incontrovertibly been established in mice. BLyS-transgenic mice often develop SLE-like features as they age [3-5], and SLE-prone (NZB NZW)F1(BWF1) and MRL-lpr/lprmice respond clinically to treatment with BLyS Raphin1 acetate antagonists (decreased Raphin1 acetate disease progression and improved survival) [3,6]. Considerable inferential evidence points to a role for BLyS overproduction in human SLE as well. Cross-sectional studies have demonstrated elevated circulating levels of BLyS in 2030% of human SLE patients tested at a single point in time [7,8]. Moreover, a 12-month longitudinal study documented persistently elevated serum BLyS levels in about 25% of SLE patients and intermittently elevated serum BLyS levels in an additional 25% of patients [9]. Remarkably, circulating BLyS levels did not correlate with disease activity (measured using the SLE Disease Activity Index [SLEDAI]) in these cross-sectional or longitudinal studies [7-9]. Although a statistically significant correlation between circulating BLyS levels and SLEDAI has been appreciated in a more recent 24-month longitudinal study of 245 SLE patients (with >1,700 plasma samples analyzed) [10], the correlation remains weak. The limited correlation between circulating BLyS protein levels and disease activity in these studies may have exposed an inadequacy of the former to reflect faithfully endogenous BLyS overproduction. In addition JNKK1 to the rate of BLyS protein production, several other factors (for example, utilization and excretion) can affect circulating BLyS protein levels. Although there are no practicable means of directly measuringin vivoBLyS productionper sein humans, the level of BLyS mRNA may serve as a better surrogate marker ofin vivoBLyS production than does the level of BLyS protein. Candidate BLyS mRNA isoforms include the full-length BLyS mRNA isoform, which encodes the full-length protein, and the alternatively spliced BLyS mRNA isoform, which encodes a protein with a small peptide deletion [11]. (BLyS does not bind to cells expressing BLyS receptors, and therefore it has no agonistic activity. Moreover, BLyS can form heterotrimers with full-length BLyS, thereby actually functioning as a dominant-negative antagonist of BLyS activity.) In this report we demonstrate that peripheral blood leukocytes from SLE patients express elevated mRNA levels of both full-length BLyS and BLyS relative to those levels expressed by patients with rheumatoid arthritis (RA) or by normal control individuals. In the SLE patients, both full-length BLyS and BLyS mRNA levels are more closely associated with disease activity (SLEDAI) than are BLyS protein levels. Accordingly, BLyS mRNA levels may be a helpful.
