Distinct Inflammatory Immune Signature in Acute Mpox Associated with Proctitis
Open Forum Infectious Diseases, 2026
Byrne J., Saini G., Garcia-Leon A., Alalwan D., Landay A., Nguyen L., Savinelli S., O’Broin C., Horgan M., Kelly C., Cotter A., Sadlier C., de Barra E., O’Halloran J., Gautier V., Mallon P., Feeney E.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology Patient Stratification | Plasma |  Olink Target 48 |
Abstract
Background
The immunopathogenesis of clade IIb Monkeypox virus (MPXV) infection and its relationship with clinical severity remains poorly defined. We characterised cytokine responses in acute and convalescent mpox to delineate inflammatory profiles.
Methods
In a multi-centre cohort, we quantified 45 plasma protein biomarkers in three adult groups; acute mpox (PCR-confirmed clade IIb MPXV infection sampled <14 days from symptom-onset), convalescent mpox (>30 days post infection) and uninfected controls matched for age, sex, race and HIV status. Biomarkers spanned innate and adaptive immune activation, systemic inflammation and tissue repair. Principal component analysis and unsupervised hierarchical clustering defined immune profiles. Associations with clinical features were explored using logistic regression.
Results
Sixteen participants with acute mpox (median 6 [4–8] days from symptom-onset; 13% vaccinated) were compared to 16 controls. Three immune clusters were identified. Cluster 1 comprised only unvaccinated acute mpox and exhibited a broad inflammatory signature (IFN-γ, CXCL9/10/11, CCL 7/8, IL-6/10, OSM). Cluster 2 displayed elevated TNFSF12 and FLT3LG, suggestive of tissue-remodelling. Cluster 3 demonstrated lower cytokine expression. Mucosal involvement was associated with the inflammatory cluster 1 (OR 7.85, 95% CI 1.02-102.40; p=0.048). Among 25 convalescent participants (median 405 [225-450] days post infection; 12% vaccinated), clustering did not distinguish cases from controls. However, targeted comparisons demonstrated persistent low-grade immune activation (IL-6, OSM) and tissue-remodelling signatures (TGF-α, VEGF-A).
Conclusions
Acute clade IIb mpox displays distinct inflammatory profiles, with systemic inflammation concentrated among those with mucosal disease. Convalescence shows partial resolution but persistent tissue-repair activity. These pathways may support risk stratification and targeted therapeutic interventions.