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Published on: February 1, 2012
Distinct Inflammatory Immune Signature in Acute Mpox Associated With Proctitis
Joanne Byrne1,2, Gurvin Saini1, Alejandro Garcia-Leon1
1Centre for Experimental Pathogen Host Research, University College Dublin, Dublin 4, Ireland.
Background:
The immunopathogenesis of clade IIb monkeypox virus (MPXV) infection and its relationship with clinical severity remain poorly defined. We characterized cytokine responses in acute and convalescent mpox to delineate inflammatory profiles.
Methods:
In a multicenter cohort, we quantified 45 plasma protein biomarkers in 3 adult groups: acute mpox (polymerase chain reaction-confirmed clade IIb MPXV infection sampled <14 days from symptom onset); convalescent mpox (>30 days postinfection); 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 via logistic regression.
Results:
Sixteen participants with acute mpox (median [IQR], 6 days [4-8] from symptom onset; 13% vaccinated) were compared with 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 remodeling. Cluster 3 demonstrated lower cytokine expression. Mucosal involvement was associated with the inflammatory cluster 1 (odds ratio, 7.85; 95% CI, 1.02-102.40; P = .048). Among 25 participants who were convalescent (median [IQR], 405 days [225-450] postinfection; 12% vaccinated), clustering did not distinguish cases from controls. However, targeted comparisons demonstrated persistent low-grade immune activation (IL-6, OSM) and tissue-remodeling 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.
Insights
Acute mpox (monkeypox virus) shows distinct inflammatory profiles, particularly in those with mucosal disease. Convalescence reveals persistent tissue repair, aiding in risk stratification and treatment strategies.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- The immunopathogenesis and clinical severity relationship of clade IIb monkeypox virus (MPXV) infection are not well understood.
- Characterizing cytokine responses in acute and convalescent mpox is crucial for defining inflammatory profiles.
Purpose of the Study:
- To delineate inflammatory profiles in acute and convalescent mpox by quantifying plasma protein biomarkers.
- To explore associations between immune profiles and clinical features of mpox.
Main Methods:
- A multicenter cohort study quantified 45 plasma protein biomarkers in acute mpox, convalescent mpox, and control groups.
- Principal component analysis and unsupervised hierarchical clustering identified immune profiles.
- Logistic regression explored associations with clinical features.
Main Results:
- Three immune clusters were identified in acute mpox; one showed broad inflammation associated with mucosal involvement (OR, 7.85; P = .048).
- Convalescent mpox did not show distinct clustering but revealed persistent low-grade immune activation and tissue-remodeling signatures.
- Vaccination status was noted in participants but did not appear to be a primary differentiator in the identified clusters.
Conclusions:
- Acute clade IIb mpox presents distinct inflammatory profiles, with systemic inflammation linked to mucosal disease.
- Convalescence is characterized by partial resolution alongside persistent tissue repair activity.
- Identified inflammatory and tissue repair pathways may inform risk stratification and targeted therapeutic interventions for mpox.
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