Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis
- 15 July 2008
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 68 (8), 1328-1333
- https://doi.org/10.1136/ard.2008.093153
Abstract
Objectives: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. Methods: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. Results: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. Conclusions: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.Keywords
This publication has 39 references indexed in Scilit:
- The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practiceAnnals Of The Rheumatic Diseases, 2007
- Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2006
- The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis populationAnnals Of The Rheumatic Diseases, 2006
- Proteome studies of CSF in AD patientsMechanisms of Ageing and Development, 2006
- Clinical practice decision tree for the choice of the first disease modifying antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the French Society of RheumatologyAnnals Of The Rheumatic Diseases, 2006
- Mass profiling-directed isolation and identification of a stage-specific serologic protein biomarker of advanced prostate cancerProteomics, 2005
- ProteinChip Technology Reveals Distinctive Protein Expression Profiles in the Urine of Bladder Cancer PatientsEuropean Urology, 2005
- Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian CancerCancer Research, 2004
- Platelet factor 4 (PF-4)–induced neutrophil adhesion is controlled by src-kinases, whereas PF-4–mediated exocytosis requires the additional activation of p38 MAP kinase and phosphatidylinositol 3-kinaseBlood, 2004
- Elevated Plasma Levels of Β-Thromboglobulin and Platelet Factor 4 in Patients with Rheumatic Disorders and Cutaneous VasculitisClinical Rheumatology, 2002