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TAM receptor ligands in lupus: protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus.

Authors
Suh, CH; Hilliard, B; Li, S; Merrill, JT; Cohen, PL
Citation
Arthritis research & therapy, 12(4):R146-R146, 2010
Journal Title
Arthritis research & therapy
ISSN
1478-63541478-6362
Abstract
INTRODUCTION : The TAM (tyro 3, axl, mer) kinases are key regulators of innate immunity and are important in the phagocytosis of apoptotic cells. Gas6 and protein S are ligands for these TAM kinases and bind to phosphatidyl serine residues exposed during apoptosis. In animal models, absence of TAM kinases is associated with lupus-like disease. To test whether human systemic lupus erythematosus (SLE) patients might have deficient levels of TAM ligands, we measured Gas 6 and protein S levels in SLE. METHODS : 107 SLE patients were recruited. Of these, 45 SLE patients were matched age, gender and ethnicity with normal controls (NC). Gas6 and free protein S were measured with sandwich enzyme linked immunosorbent assays (ELISAs). RESULTS : Overall, the plasma concentrations of Gas6 and free protein S were not different between 45 SLE patients and 45 NC. In SLE patients, the levels of free protein S were positively correlated with age (r = 0.2405, P = 0.0126), however those of Gas6 were not. There was no correlation between the concentrations of Gas6 and free protein S in individuals. Levels of free protein S were significantly lower in SLE patients with a history of serositis, neurologic disorder, hematologic disorder and immunologic disorder. Gas6 levels were elevated in patients with a history of neurologic disorder. The SLE patients with anti-Sm or anti-cardiolipin IgG showed lower free protein S levels. Circulating free protein S was positively correlated with complement component 3 (C3) (r = 0.3858, P < 0.0001) and complement component 4 (C4) (r = 0.4275, P < 0.0001). In the patients with active BILAG hematologic involvement, the levels of free protein S were lower and those of Gas6 were higher. CONCLUSIONS : In SLE, free protein S was decreased in patients with certain types of clinical history and disease activity. Levels of free protein S were strongly correlated with C3 and C4 levels. Gas6 levels in SLE patients differed little from levels in NC, but they were elevated in the small numbers of patients with a history of neurological disease. The correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation. Protein S appears more important functionally in SLE patients than Gas6 in this regard.
MeSH terms
AdultApoptosis/immunologyBiological Markers/bloodComplement C3/metabolismComplement C4/metabolismEnzyme-Linked Immunosorbent AssayFemaleHumansIntercellular Signaling Peptides and Proteins/*bloodLigandsLupus Erythematosus, Systemic/immunology/*metabolismMaleMiddle AgedProtein S/*metabolismProto-Oncogene Proteins/immunology/metabolismReceptor Protein-Tyrosine Kinases/immunology/*metabolismSeverity of Illness IndexYoung Adult
DOI
10.1186/ar3088
PMID
20637106
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Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
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