Streptococcal Serology Reference Intervals in an Australian Pediatric Cohort.

Background: Diagnostic criteria for acute rheumatic fever and post-streptococcal glomerulonephritis, the 2 major autoimmune complications of Streptococcus pyogenes infection, include serological evidence of preceding infection. The S. pyogenes proteins, namely streptolysin O and deoxyribonuclease B, are the most widely used targets for clinical streptococcal serology. We aimed to establish age-based reference intervals (RIs) for healthy children in Victoria, Australia, to guide interpretation of anti-streptolysin O (ASO) levels measured by turbidimetry and nephelometry, and anti-deoxyribonuclease B (ADB) levels by nephelometry.

Methods: Serum samples were collected from healthy pediatric cohorts aged 32-week gestation to <18 years at 4 hospitals in Melbourne, Australia, between February 2015 and October 2018. Anti-streptolysin O levels were measured in 2 cohorts: by turbidimetry in cohort 1 and by nephelometry in cohort 2. Anti-deoxyribonuclease B levels were measured by nephelometry in cohort 2. Reference intervals (RIs) for each age group were generated, including 80% upper limit of normal (ULN) cut-offs.

Results: Anti-streptolysin O 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. Anti-streptolysin O levels, measured by turbidimetry, were highest in children 5-9 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 10-14 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.