No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE

Abstract

Altered function of selectin glycoprotein adhesion molecules may modulate severity and organ-specific manifestations of autoimmune and inflammatory disease via changes in leukocyte trafficking. Serum concentrations of selectin molecules have been suggested as useful biomarkers in systemic lupus erythematosus (SLE). We identified increased levels of soluble L-selectin (sL-selectin), but not soluble E-selectin (sE-selectin) in 278 European-Caucasian lupus patients compared to 230 healthy siblings (P ¼ 0.002). sL-selectin levels were markedly elevated in patients with IgG antiphospholipid autoantibodies (P ¼ 0.002), suggesting that perhaps sL-selectin defines a subgroup of lupus with vasculopathy. sL-selectin level was also influenced by two L-selectin polymorphisms: 665C4T, F206L in the epidermal growth factor-like domain (P ¼ 0.015) and rs12938 in the 3 0 -untranslated region (P ¼ 0.06). Having shown increased sL-selectin levels in lupus patients, we used genetics to investigate whether this was a secondary phenomena or the result of an underlying genetic mechanism. The inheritance of nine single-nucleotide polymorphisms (SNP) spanning the selectin locus was tested in 523 UK simplex SLE families. No association with SLE, or related phenotypes, was evident with any single SNP, or haplotype in family-based tests of association. Selectin polymorphisms are, therefore, unlikely to be independent factors in SLE susceptibility.

Effect of Interleukin-15 on CD11b, CD54, and CD62L Expression on Natural Killer Cell and Natural Killer T-Like Cells in Systemic Lupus Erythematosus

“…CD62L belongs to a member of selectins that is important for NK cells homing to the lymph nodes and also an important marker for NK maturation and response to viral infections [23]. Previous studies have shown that circulating soluble CD54 and CD62L correlated with SLE disease activity [24, 25]. …”

Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE

“…We have already studied these two genes and found no evidence of association with SLE, although two variants in the EGF domain were associated with the levels of soluble L-Selectin. 9 All three selectin genes are located in a gene cluster on chromosome 1. The selectin molecules begin with an N-terminal, 'lectin' domain followed by an 'EGF' domain, nine tandem consensus repeats similar to those in complement-binding proteins, a transmembrane domain and a cytoplasmic tail.…”

Assessment of theE-Selectinrs5361 (561A>C) Polymorphism and Soluble Protein Concentration in Acute Coronary Syndrome: Association with Circulating Levels

“…Even though our sample size was similar to Macías et al 2003 (16 versus 11), we could not confirm this conclusion since the difference did not reach a statistical significance (data not shown). Some researchers have suggested that soluble levels of E-selectin are gender dependent, being higher in men [68–71]. To test whether age and gender could be introducing bias in our results, the soluble levels of E-selectin were adjusted by age and gender (Table 3) without any significant evidence ( P > 0.27), reinforcing that higher levels are related with the disease group tested in this study.…”