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Series GSE217351 Query DataSets for GSE217351
Status Public on Nov 04, 2022
Title CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Organism Homo sapiens
Experiment type Protein profiling by protein array
Summary Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N=42), patients with iMCD (N=88), and with related diseases (N=60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD.
 
Overall design Samples were collected from 98 iMCD patients – including 79 patients who participated in the phase II registrational trial for siltuximab (NCT01024036) and 19 additional patients experiencing active disease. The 79 patients in the trial were randomized to placebo (N=26) or to siltuximab (N=53). Samples were collected from all iMCD patients before siltuximab treatment. Additionally, longitudinal samples at day 8 and day 64 of siltuximab treatment were collected from the iMCD patients in the phase II trial. One time samples were collected from comparator groups including 44 healthy donors, recruited to serve as age- and sex-matched comparators to the iMCD group and 20 patients each with clinico-pathologically overlapping disorders rheumatoid arthritis (RA), Hodgkin lymphoma (HL), and HIV-positive, HHV8-associated MCD (HHV8-MCD)—a form of MCD that is caused by uncontrolled infection with HHV8— representing diseases of autoimmune, neoplastic, and infectious origin respectively. Quantification of 1,305 protein analytes in the Primary cohort was performed by SomaLogic SOMAscan 1.3k version, a DNA-based aptamer technology per manufacturer’s protocol. Due to the number of samples, quantification was performed in two batches, and five technical replicates were included between the two batches. Batches were bridged together by the average log ratio of technical replicates for each analyte. SomaLogic SOMAscan pre-processing was performed, and 1,178 analytes passed quality control. Following quality control sample exclusion, pretreatment samples available for analysis included 88 iMCD patients, 42 healthy donors, and 20 each of RA, HL, and HHV8-MCD. Longitudinal samples available for analysis included samples from day 8 and day 64 of treatment from 73 iMCD patients.
 
Contributor(s) Fajgenbaum DC, Pierson SK, Katz L
Citation(s) 36433996
Submission date Nov 04, 2022
Last update date Dec 15, 2022
Contact name David Fajgenbaum
E-mail(s) Davidfa@pennmedicine.upenn.edu
Organization name University of Pennsylvania
Department Medicine
Lab Center for Cytokine Storm Treatment & Laboratory (CSTL)
Street address 3535 Market St, 717
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL23119 SOMAscan human proteomic assay [SOMAscan Assay 1.3k]
Samples (368)
GSM6715330 Patient_1, Serum, HIV/HHV-8+
GSM6715331 Patient_2, Serum, HIV/HHV-8+
GSM6715332 Patient_3, Serum, HIV/HHV-8+
Relations
BioProject PRJNA898421

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE217351_2.15_JRD_16-166.hybNorm.medNorm.calibrate.20160923.adat.txt.gz 871.7 Kb (ftp)(http) TXT
GSE217351_2.5_PX-17-116.HybMedNormCal.Premium.adat.txt.gz 568.5 Kb (ftp)(http) TXT
GSE217351_JRD16.txt.gz 808.8 Kb (ftp)(http) TXT
GSE217351_JRD17.txt.gz 499.5 Kb (ftp)(http) TXT
Processed data included within Sample table
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