Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Expanded Cytokine/Chemokine Testing Improves Prediction of Time to Future Diagnosis of Seropositive Rheumatoid Arthritis (RA) in an Age-Dependent Manner.

Deane8,  Kevin D., O'Donnell2,  Colin I., Derber3,  Lezlie A., Edison10,  Jess D., Gilliland1,  William R., Hueber4,  Wolfgang, Sokolove6,  Jeremy

Department of Medicine, Rheumatology Section, Walter Reed Army Medical Center, Washington, DC
Walter Reed Army Med Ctr, Washington, DC
Department of Preventive Medicine and Biometrics, University of Colorado Denver, Denver, CO
Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO
Novartis Institutes for BioMedical Research, Basel, Switzerland
Stanford Univ School of Med, Stanford, CA
Stanford University School of Medicine, Palo Alto, Mountain View, CA
Stanford University School of Medicine, Palo Alto, CA
Univ of Colorado School of Med, Aurora, CO
University of Colorado Denver, Aurora, CO

Purpose:

We have previously shown using testing for 14 cytokines/chemokines that the number of elevated cytokines/chemokines predicted time to diagnosis of future RA in an age-dependent manner. However, with this limited number of cytokines/chemokines, accurate prediction was limited to <5 years prior to RA diagnosis. Herein we examine the effect of testing for increased numbers of cytokines/chemokines (N=48 current versus 14 prior) on the prediction of time to diagnosis of future RA.

Methods:

For this analysis we selected 101 stored pre-RA diagnosis serum samples from 51 military cases (69% male, mean age at RA diagnosis 39) that would develop future rheumatoid factor (RF) and/or CCP positive RA. These pre-diagnosis samples were selected based on positivity for anti-CCP and/or 2 or more RF isotypes, an autoantibody profile shown prior to have 74% sensitivity and >96% specificity for future RA. Each of these pre-diagnosis samples was tested for 48 cytokines/chemokines using a magnetic bead-based assay. Cytokine/chemokine positivity was established using additional military post-RA diagnosis case versus matched control samples (N=43 each group), with cutoff levels selected for positivity >90% specific for RA. The time from pre-diagnosis sample collection to RA diagnosis was analysed using mixed-model regression analysis, with predictor variables age-at-diagnosis (stratified by decade) and cyotkine/chemokine counts.

Results:

The number of elevated cytokines/chemokines (cytokine/chemokine counts) increased as the time of diagnosis of RA approached, with the highest cytokine/chemokine counts present <2 years prior to RA diagnosis. Increasing cytokine/chemokine counts predicted time to diagnosis in an age-dependent manner (Figure). The regression coefficients for age-at-diagnosis (by decade) and cytokine/chemokine counts were respectively beta1=-0.975 (p<0.01) and beta2= 0.147 (p<0.01). In contrast to prior analysis with 14 markers, testing for 48 markers allowed for accurate prediction of time of onset of future RA more than 6 years prior to diagnosis as well as allowing for finer prediction of time to diagnosis in times <3 yrs prior to diagnosis.

Increasing Cytokine/Chemokine Counts Predict Time to Future Diagnosis of Seropositive Rheumatoid Arthritis. All subject samples (N=101 from 51 RA cases) included in this analysis were positive for anti-CCP and/or 2 or more RF isotypes, an autoantibody profile >96% specific for future RA. In regression analysis, time to diagnosis for future RA was the outcome, and cytokine/chemokine counts and age (by decade) were predictor variables. For example, in a subject 45 years-old at assessment, a cytokine/chemokine count of 30 positive predicts a time to diagnosis of future RA of ~2 years.

Conclusions:

In pre-clinical case samples positive for autoantibodies highly specific for future RA, increasing cytokine/chemokine counts from a panel of 48 cytokines/chemokines predicts time-to-diagnosis in an age-dependent manner, improving a prior model using 14 cytokines/chemokines. These findings provide insight into the biology of pre-clinical RA as well as provide a methodology for identification of currently arthritis-free subjects at risk for imminent RA who may be candidates for intervention studies.

To cite this abstract, please use the following information:
Deane, Kevin D., O'Donnell, Colin I., Derber, Lezlie A., Edison, Jess D., Gilliland, William R., Hueber, Wolfgang, et al; Expanded Cytokine/Chemokine Testing Improves Prediction of Time to Future Diagnosis of Seropositive Rheumatoid Arthritis (RA) in an Age-Dependent Manner. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1083
DOI: 10.1002/art.28850

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