dThe disease spectrum caused by Streptococcus dysgalactiae subsp. equisimilis resembles that of S. pyogenes (group A streptococcus [GAS]). These two bacterial species are closely related and possess many common virulence characteristics. While some GAS strains express virulence factors called streptococcal inhibitor of complement (SIC) and distantly related to SIC (DRS), some S. dysgalactiae subsp. equisimilis isolates express an orthologue of DRS, which is referred to as DRS-G. We reported previously that seropositivity for either anti-SIC or anti-DRS antibodies (Abs) is associated with poststreptococcal glomerulonephritis (PSGN). However, only seropositivity for anti-SIC Abs is associated with chronic kidney disease (CKD). We now extend the study to test whether seropositivity for anti-DRS-G Abs is also associated with these renal diseases. Stored serum samples collected for our previous study were tested by an enzyme-linked immunosorbent assay (ELISA) for Abs to DRS-G. The samples represented sera from 100 CKD adult patients, 70 adult end-stage renal disease (ESRD) patients, 25 PSGN pediatric patients, and corresponding age-matched control subjects. The proportion of PSGN, CKD, and ESRD patients who showed seroreaction to anti-DRS-G Abs was significantly higher than that of the corresponding age-matched controls, who in general exhibited seropositivity rates commensurate with the isolation rate of drsG-positive S. dysgalactiae subsp. equisimilis in the community during this study period. Since higher rates of seropositivity for anti-DRS-G Abs in the renal disease categories are resultant of previous infections with DRS-G-positive S. dysgalactiae subsp. equisimilis strains, we conclude the seropositivity is an additional risk factor for these renal diseases. In this regard, anti-DRS-G Abs have attributes similar to those of the anti-SIC Abs.S treptococcus dysgalactiae subsp. equisimilis was often not regarded as a human pathogen in the past, but it is now being recognized as a significant human pathogen, with an increasing frequency of reports of epidemiological observations (1-4). S. pyogenes (group A streptococcus [GAS]) and S. dysgalactiae subsp. equisimilis are associated with similar disease spectra, including the immune system-mediated postinfectious sequela poststreptococcus glomerulonephritis (PSGN) (1, 5). Comparative genomic studies revealed that these two pathogens are genetically related, with many common virulence factors (6, 7).Among the virulence factors produced by S. dysgalactiae subsp. equisimilis is a secretory protein called DRS-G. This protein has limited primary sequence homology with SIC (streptococcal inhibitor of complement) and DRS (distantly related to SIC) in GAS (6). As might be expected, DRS-G exhibits limited functional overlap with SIC and DRS. For instance, unlike SIC, DRS-G does not inhibit complement-mediated cell lysis. In this regard, DRS-G resembles DRS. However, like DRS and SIC, DRS-G inhibits the antimicrobial peptide LL37 (8).Several studies (9-11) have shown that posi...