title: Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis.
abstract: BACKGROUND
  Thrombopoietin (TPO) is a liver-produced protein that drives megakaryocyte maturation. TPO regulates platelet production and can increase platelet and endothelial reactivity. We investigated the relationship between TPO and the occurrence of thrombocytopenia and thrombosis in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  We undertook a cohort study of SLE patients (n = 98) with clinical data collected simultaneously with sampling for TPO, inflammatory cytokines and autoantibody detection. TPO levels were measured by sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and controls (n = 79) as comparators. Disease associations were evaluated using non-parametric methods.
  
  
  RESULTS
  TPO levels in SLE (median 8 pg/ml, mean 326, range 8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range 1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE patients, TPO levels did not correlate with platelet count or levels of antiphospholipid antibodies. The prevalence of thrombocytopenic episodes, thrombotic events or active disease was not increased in patients with high TPO levels. TPO levels correlated with MIP-1α (Rs 0.56, p < 0.001), IL6 (Rs 0.26, p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23, p = 0.04). MIP-1α was the strongest independent predictor of increased TPO levels.
  
  
  CONCLUSIONS
  TPO levels are elevated in 20% of patients, but are not closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1-alpha is the main factor driving higher TPO levels among patients with SLE, likely through its inhibitory effect on megakaryocyte function.
authors.affiliation: Rheumatology Section, Div. Medicine, Royal Darwin Hospital, Darwin, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.affiliation: Rheumatology Section, Div. Medicine, Royal Darwin Hospital, Darwin, Australia Bone & Joint Group, Dept. Clinical Medicine, Faculty Health Sciences University Tromsø, Norway Rheumatology Dept., School of Medicine & Pharmacology, University of Western Australia, Perth, WA, Australia Johannes.nossent@uwa.edu.au.
authors.forename: J
authors.initials: J
authors.lastname: Nossent
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000097:blood; D015331:Cohort Studies; D003181:Complement C4 / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D013921:Thrombocytopenia / Q000097:blood* / Q000150:complications; D013926:Thrombopoietin / Q000097:blood*; D013927:Thrombosis / Q000097:blood* / Q000150:complications; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D003181:Complement C4; D016207:Cytokines; D015850:Interleukin-6; D015847:Interleukin-4; D004247:DNA; D013926:Thrombopoietin
keywords: SLE; Thrombopoietin; cytokines; platelets; thrombosis