title: Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients.
abstract: Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1-32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Groningen Research initiative on healthy Ageing and Immune Longevity (GRAIL) University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Paulina
authors.initials: P
authors.lastname: Chalan
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bijzet
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Kluiver
authors.affiliation: Groningen Research initiative on healthy Ageing and Immune Longevity (GRAIL) University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kroesen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Groningen Research initiative on healthy Ageing and Immune Longevity (GRAIL) University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Annemieke M H
authors.initials: AM
authors.lastname: Boots
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Groningen Research initiative on healthy Ageing and Immune Longevity (GRAIL) University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
mesh_terms: D000328:Adult; D000368:Aged; D018771:Arthralgia / Q000175:diagnosis* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D044967:Serum / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D016207:Cytokines