Innate immune response gene expression profiles characterize primary antiphospholipid syndrome.
Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder characterized by thromboembolic episodes and pregnant morbidity with an increasing clinical importance. To gain insight into the pathogenesis of PAPS, we have investigated the gene expression profiles that characterize peripheral blood mononuclear cells derived from PAPS patients. We show that the transcriptional activity of genes involved in innate immune responses, such as toll-like receptor 8 and CD14, as well as downstream genes of this pathway, such as STAT1, OAS2, TNFSF13 and PLSCR1 are significantly increased in PAPS patients. In addition, the expression of monocyte-specific cytokines is also elevated in PAPS mononuclear cells stimulated in vitro with lipopolysaccharide. Taken together, these results reveal a 'response to pathogen' signature in PAPS, which could reflect an altered monocyte activity. Finally, microarray analyses also revealed a reduced expression of genes coding for proteins involved in transcriptional control. Interestingly, a significant proportion of them exhibit E2F-binding sites in their promoter, suggesting that a deregulated RB/E2F activity could play a role in the pathogenesis of antiphospholipid syndrome.
Bernales
I
I
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Bilbao, Spain.
Fullaondo
A
A
Marín-Vidalled
M J
MJ
Ucar
E
E
Martínez-Taboada
V
V
López-Hoyos
M
M
Zubiaga
A M
AM
D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000209:etiology / Q000276:immunology*; D001665:Binding Sites; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D050704:E2F4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D016207:Cytokines; D050704:E2F4 Transcription Factor; D008070:Lipopolysaccharides; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8