Plasma proteomics identifies a 'chemokine storm' in idiopathic multicentric Castleman disease.
Level 4 - case-series / case-control
Case series with paired biomarker profiling during flare and remission
PubMed 29675946 · doi:10.1002/ajh.25123
What was done
Quantification of 1129 proteins across 13 plasma samples collected during flare and remission from 6 patients with idiopathic multicentric Castleman disease (2 with iMCD-TAFRO and 4 with iMCD-NOS). CXCL13 expression in lymph node germinal centers was also compared with controls.
What was found
NPS-PLA2 was the only significantly increased protein (P = .017). Chemokines and complement were significantly enriched pathways. CXCL13 was the most upregulated cytokine across all patients (log2 fold-change = 3.22) and was significantly increased in lymph node germinal centers in a stromal meshwork pattern. Distinct proteomic profiles were observed between the 2 iMCD-TAFRO patients (both anti-IL-6 nonresponders) and 4 iMCD-NOS patients (all 3 treated responded to anti-IL-6).
Why it matters
Highlights a chemokine-driven signature led by CXCL13 in iMCD flares, pointing toward alternative pathogenic pathways and potential therapeutic targets for patients who do not respond to IL-6 blockade.
Limits
Extremely small sample size (n = 6 patients, 13 total plasma samples), subgroup comparisons are limited to 2 vs. 4 patients, and specific control group characteristics are not detailed in the abstract.
Cited by
- supports Castleman disease is an atypical lymphoproliferative disorder where hyperactivated immune cells produce cytokines that cause vital organ failure.