Streptococcal serology reference intervals in an Australian pediatric cohort.

Background: Diagnostic criteria for acute rheumatic fever and post-streptococcal glomerulonephritis, the two major autoimmune complications of Streptococcus pyogenes infection, include serological evidence of preceding infection. The S. pyogenes proteins streptolysin O (ASO) and deoxyribonuclease B (ADB) are the most widely used targets for clinical streptococcal serology. We aimed to establish age-based reference intervals (RI) for healthy children in Victoria, Australia, to guide interpretation of anti-streptolysin O levels measured by turbidimetry and nephelometry, and anti-deoxyribonuclease B levels by nephelometry. MethodsSerum samples were collected from healthy pediatric cohorts aged 32 weeks gestation to < 18 years at 4 hospitals in Melbourne, Australia, between February 2015 and October 2018. ASO levels were measured in two cohorts, by turbidimetry in Cohort 1, and by nephelometry in Cohort 2. ADB levels were measured by nephelometry in Cohort 2. Reference intervals (RI) for each age group were generated, including 80% upper limit of normal (ULN) cut-offs.

Results: ASO levels were measured by turbidimetry for 359 samples from Cohort 1, and ASO and ADB levels were measured by nephelometry for 360 samples from Cohort 2. ASO levels, measured by turbidimetry, were highest in children 5 to 9 years of age (80% ULN 346 IU/mL) in Cohort 1. For Cohort 2, there was a linear age-related increase in ASO levels measured by nephelometry (80% ULN 426 IU/mL in those 15 to < 18 years old) and ADB levels were highest in children aged 10 to 14 years (80% ULN 454 IU/mL).

Conclusions: We established age-specific RI for ASO and ADB levels measured by turbidimetry and nephelometry for healthy Australian children. This study highlights the importance of local method-specific age-based RI to interpret ASO and ADB levels when clinicians suspect acute rheumatic fever or post-streptococcal glomerulonephritis in children.