The Human Immune Response to Streptococcal Extracellular Antigens: Clinical, Diagnostic, and Potential Pathogenetic Implications

Abstract

Background. Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti–streptolysin O and anti–DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Methods. Pediatric study participants (n=160) were followed during a 2-year study with monthly throat cultures (n=3491) and blood samples (n=1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti–streptolysin O and anti–DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. Results. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, “upper limit of normal”), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Conclusions. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.