RGD Reference Report - Elevated expression of platelet-derived chemokines in patients with antiphospholipid syndrome. - Rat Genome Database

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Elevated expression of platelet-derived chemokines in patients with antiphospholipid syndrome.

Authors: Patsouras, Markos D  Sikara, Marina P  Grika, Eleftheria P  Moutsopoulos, Haralampos M  Tzioufas, Athanasios G  Vlachoyiannopoulos, Panayiotis G 
Citation: Patsouras MD, etal., J Autoimmun. 2015 Dec;65:30-7. doi: 10.1016/j.jaut.2015.08.001. Epub 2015 Aug 15.
RGD ID: 401794584
Pubmed: PMID:26283469   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jaut.2015.08.001   (Journal Full-text)


OBJECTIVE: Platelet factor 4 tetramers (CXCL4 chemokine) form complexes with β2glycoprotein I (β2GPI), recognized by anti-β2GPI antibodies leading to platelet activation in antiphospholipid syndrome (APS), either primary (PAPS) or secondary (SAPS). Increased plasma levels of CXCL4 may favor this process; therefore we measured plasma levels of CXCL4, a CXCL4 variant (CXCL4L1) and as controls, platelet-derived chemokines CXCL7 (NAP-2) and CCL5 (RANTES), in APS, and disease controls such as patients with systemic lupus erythematosus (SLE) coronary artery disease (CAD) and healthy donors (HDs).
METHODS: Plasma samples and platelets were isolated from patients with APS (n = 87), SLE (n = 29), CAD (n = 14) and 54 HDs. Plasma levels of CXCL4, CXCL4L1, CXCL7 and CCL5 as well as intracellular platelet CXCL4 and CXCL4L1 were measured using ELISA. Platelet CXCL4 and CXCL4L1 RNA levels were determined by RT-PCR.
RESULTS: CXCL4, CXCL7 (NAP-2) and CCL5 (RANTES) plasma levels were significantly higher in patients with APS compared to both control groups (SLE, CAD) and HDs. CXCL4L1 plasma levels were also significantly higher in APS than in SLE and HDs, but lower from that of CAD patients. Statistically significant concordance was detected between CXCL4 and CXCL7 (p < 0.0001) or CCL5 (p < 0.0001) plasma levels in patients with APS, either PAPS or SAPS. CXCL4L1 plasma levels were inversely correlated with CXCL4 (P = 0.0027), CXCL7 (p = 0.012) and CCL5 (p = 0.023) in PAPS and positively with CXCL4 (p = 0.0191), CCL5 (p < 0.0001) and CXCL7 (P < 0.0001), in SAPS. Levels of CXCL4, CXCL4L1, CXCL7 and CCL5 were divided in "high" (exceeding a level defined as the mean of HDs and 3 SD) and "low" (below this level); The "CXCL4L1 high" group was characterized by increased IgG aCL, (p = 0.0215), double antibody positivity (either aCL or anti-β2GPI plus LA), (p = 0.0277), triple antibody positivity (aCL plus anti-β2GPI plus LA), (p = 0.0073) and thrombocytopenia (p = 0.0061), as well as with at least 1 thrombotic event or the last 5 years (p = 0.0001), or more than 3 thrombotic events ever (p = 0.0151).
CONCLUSIONS: Chemokines associated with platelet activation and immune cell chemotaxis were found to be elevated in APS patients' plasma and may contribute to the pathogenesis of the syndrome. High CXCL4L1 plasma levels are associated with the clinical expression of APS and should be prospectively evaluated as a biomarker.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
antiphospholipid syndrome  IEP 401794584; 401794584; 401794584protein:increased expression:plasmaRGD 
antiphospholipid syndrome  ISOCCL5 (Homo sapiens)401794584; 401794584protein:increased expression:plasmaRGD 
antiphospholipid syndrome severityIEP 401794584 RGD 
antiphospholipid syndrome  ISOPF4 (Homo sapiens)401794584; 401794584protein:increased expression:plasmaRGD 
antiphospholipid syndrome  ISOPPBP (Homo sapiens)401794584; 401794584protein:increased expression:plasmaRGD 
coronary artery disease  IEP 401794584protein:increased expression:plasmaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl5  (C-C motif chemokine ligand 5)
Pf4  (platelet factor 4)
Ppbp  (pro-platelet basic protein)

Genes (Mus musculus)
Ccl5  (C-C motif chemokine ligand 5)
Pf4  (platelet factor 4)
Ppbp  (pro-platelet basic protein)

Genes (Homo sapiens)
CCL5  (C-C motif chemokine ligand 5)
PF4  (platelet factor 4)
PF4V1  (platelet factor 4 variant 1)
PPBP  (pro-platelet basic protein)

Objects referenced in this article
Gene CCL7 C-C motif chemokine ligand 7 Homo sapiens
Gene Ccl7 C-C motif chemokine ligand 7 Mus musculus
Gene Ccl7 C-C motif chemokine ligand 7 Rattus norvegicus

Additional Information