Session Title: Genetics, Genomics and Proteomics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Psoriatic arthritis (PsA) is a potentially destructive disease that develops in about 30% of patients with cutaneous psoriasis. Biomarkers that can predict which psoriasis patients are destined to develop PsA may help early diagnosis of PsA. This study aimed to determine if T cell and NK cell-associated cytokines IFNA2, IL-15, IL-17A, IL-23, and TRAIL, and chemokine CXCL10, are elevated in the serum of psoriasis patients who progress to develop PsA, compared to psoriasis patients who do not develop PsA.
Methods: Psoriasis patients were followed prospectively beginning in 2006, and were assessed yearly by a rheumatologist for the presence of PsA. Psoriasis patients who developed PsA were termed ‘converters’, and serum samples were taken at baseline from all and again at PsA diagnosis from a subset of converters. Age and sex-matched patients who did not develop PsA over the same duration of psoriasis were termed ‘non-converters’. Serum CXCL10, IFNA2, IL-15, IL-17A, IL-23, and TRAIL were measured using a multiplexed microsphere-based assay on the Luminex 200 platform. Protein levels were compared between samples taken before and after PsA diagnosis by paired t-test, and between converters and non-converters by logistic regression.
Results: Forty-six psoriasis patients developed PsA. At baseline, these converters were 54.3% males, with a mean age of 46.1 ± 13.0 years, mean psoriasis duration of 25.5 ± 14.9 years, mean age at psoriasis onset of 20.9 ± 16.5 years, and mean PASI of 7.0 ± 7.2. Converters were compared to 46 non-converters who were 50% males, with a mean age of 45.5 ± 12.3 years, mean psoriasis duration of 27.5 ± 16.0 years, mean age at psoriasis onset of 18.9 ± 16.3 years, and mean PASI of 6.3 ± 6.1. Candidate biomarkers were first tested in half of the converter and non-converter samples (discovery cohort), then were validated in the remaining samples. In the discovery cohort, CXCL10 was significantly elevated in baseline samples from converters compared to non-converters (OR=1.6, 95% CI 1.2-2.2, p=0.005). TRAIL was also elevated in converters at baseline (OR=1.0, 95% CI 1.0-1.1, p=0.05) however it was not independent of CXCL10 in multivariate analyses. IFNA2, IL-15, IL-17A, and IL-23 were below the detectable range in several samples and were not significant. CXCL10 remained significantly elevated (OR=1.3, 95% CI 1.1-1.5, p=0.003) in a combined analysis of the discovery and validation cohorts. Twenty-three converters had samples taken at both baseline and at PsA diagnosis. Although mean CXCL10 level was high in baseline samples, it declined significantly following PsA onset from 932 ± 458 pg/ml to 543 ± 310 pg/ml (p<0.001), which is not significantly different from the mean CXCL10 levels observed in non-converters (421 ± 218 pg/ml, p=0.06).
Conclusion: We demonstrated that CXCL10 was elevated in the serum of psoriasis patients who later developed PsA, but following PsA onset returned to levels closer to those observed in psoriasis patients who did not develop PsA. Further studies are needed to elucidate of the dynamics of serum CXCL10 levels in the progression from psoriasis to PsA, and to determine how well CXCL10 levels indicate PsA risk in psoriasis patients.
D. D. Gladman,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-c-x-c-motif-chemokine-10-cxcl10-is-elevated-in-psoriasis-patients-prior-to-psoriatic-arthritis-onset/