Endoscopic subureteral collagen injection: are immunological concerns justified?

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.