Endoscopic subureteral collagen injection: are immunological concerns justified?

Abstract

Purpose: We evaluated the humoral immune response in children treated with subureteral collagen injection for vesicoureteral reflux by analyzing serum for anticollagen antibodies.

Materials and methods: We obtained serum before skin testing and at intervals after subureteral collagen injection in 7 girls and 3 boys with a mean age plus or minus standard error of 9.2+/-1.4 years. Serum antibody titers to bovine collagen, and human collagen types I and III were determined by indirect enzyme-linked immunosorbent assay. Patients were assessed for adverse reactions related to an immune response to collagen.

Results: Followup ranged from 14 to 40 months (mean 24.6) after the initial subureteral collagen injection. One to 4 subureteral collagen injections were given with cumulative collagen volume per patient ranging from 0.15 to 5.1 cc (mean 2.1). In 2 cases no baseline serum sample was obtained. Antibody titers measured in the 8 other patients before skin testing revealed equivocal and negative results in 5 and 3 for antibovine collagen, and in 1 and 7 for antihuman collagen types I and III, respectively. At the last followup results were positive, equivocal and negative in 3, 5 and 2 for antibovine collagen, and in 0, 2 and 8 for antihuman collagen types I and III, respectively. Seroconversion developed 13 to 24 months after the initial subureteral collagen injection in antibovine collagen seropositive patients, including 1 with a limited episode of bladder irritability after seroconversion. No other patient had adverse events considered to be immunological.

Conclusions: In 3 of the 10 children treated with subureteral collagen injection for vesicoureteral reflux serum antibodies to bovine collagen developed. The volume of collagen injected was small, suggesting that volume is not a major determinant of immunogenicity. In 1 patient with seroconversion a local reaction may have been immunogenic. No patient had systemic symptoms of autoimmune disease and there was no seroconversion to antibodies cross-reacting with human collagen.