Abstract

BackgroundStreptococcal infections are known to trigger autoimmune disorders, affecting millions worldwide. Recently, we found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance. This led us to evaluate associations between post-streptococcal antibodies and metabolic syndrome, as defined by the updated National Cholesterol Education Program definition, 2005.Methods and FindingsMetabolic data (HDL, triglycerides, fasting glucose, blood pressure, waist circumference, BMI, smoking), post-streptococcal antibodies (anti-Streptolysin O (ASO) and anti-PDI), and C-reactive protein (CRP, as a general inflammatory marker), were assessed in 1156 participants of the Wisconsin Sleep Cohort Study. Anti-PDI antibodies were found in 308 participants (26.6%), ASO≥100 in 258 (22.3%), and 482 (41.7%) met diagnostic criteria for metabolic syndrome. Anti-PDI antibodies but not ASO were significantly associated with metabolic syndrome [n = 1156, OR 1.463 (95% CI 1.114, 1.920), p = 0.0062; adjusted for age, gender, education, smoking]. Importantly, the anti-PDI - metabolic syndrome association remained significant after adjusting for CRP and fasting insulin.ConclusionsPost-streptococcal anti-PDI antibodies are associated with metabolic syndrome regardless of fasting insulin and CRP levels. Whereas these data are in line with a growing body of evidence linking infections, immunity and metabolism, additional studies are necessary to establish the post-streptococcal – metabolic syndrome association.

Highlights

  • Metabolic syndrome is characterized by a cluster of metabolic risk factors for cardiovascular diseases and type 2 diabetes that include abdominal obesity, dyslipidemia, hypertension, insulin resistance, prothrombotic and proinflammatory state

  • Post-streptococcal anti-Protein Disulphide Isomerase (PDI) antibodies are associated with metabolic syndrome regardless of fasting insulin and CRP levels

  • We reported that a subset of patients with poststreptococcal immunity, as defined by the presence of antiStreptolysin O (ASO) or anti-DNase B (ADB) antibodies carry auto-antibodies against Protein Disulfide Isomerase (PDI), a pleiotropic enzyme

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Summary

Introduction

Metabolic syndrome is characterized by a cluster of metabolic risk factors for cardiovascular diseases and type 2 diabetes that include abdominal obesity, dyslipidemia, hypertension, insulin resistance, prothrombotic and proinflammatory state. We reported that a subset of patients with poststreptococcal immunity, as defined by the presence of antiStreptolysin O (ASO) or anti-DNase B (ADB) antibodies carry auto-antibodies against Protein Disulfide Isomerase (PDI), a pleiotropic enzyme. We found that these auto-antibodies neutralize PDI, decrease insulin degradation and correlate with higher insulin levels and insulin resistance [3]. We found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance This led us to evaluate associations between post-streptococcal antibodies and metabolic syndrome, as defined by the updated National Cholesterol Education Program definition, 2005

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