Suppressor of Variegation 3-9 Homologue 1 Impairment and Neutrophil-skewed Systemic Inflammation Are Associated with Comorbidities in COPD

Abstract

BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD.METHODS: To assess whether impaired SUV39H1 expression in COPD patients leads to neutrophilic inflammation, downstream responses to IL-8 and suppression of Th2 responses, the SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy subjects and 30 COPD patients were measured by immunoblotting. Clinical outcomes associated with SUV39H1-related inflammation were also studied. The relationships between SUV39H1 and neutrophil or eosinophil (Th2 response) counts and clinical outcomes were evaluated. In an extended COPD cohort (213 patients), association analyses of blood cell counts with comorbidities and exacerbations were performed.RESULTS: Low SUV39H1 expression was associated with high neutrophil counts and a trend towards low eosinophil counts. In the extended cohort, the high comorbidity group had higher neutrophil counts than the low comorbidity group but similar whole white blood cell counts. The eosinophil percentage and eosinophil/neutrophil ratio displayed contrasting results. The proportion of neutrophils was correlated with COPD comorbidities. Patients with 0-1 moderate to severe exacerbations in the past year had numbers of neutrophils and eosinophils similar to those of patients who experienced more than an exacerbation. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities.CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.