Reactivity of sera from patients with liver disease with glutaraldehyde-treated erythrocytes: role for false positive results in hemagglutination tests.

The use of glutaraldehyde as a coupling reagent in the passive hemagglutination test (HA) has gained wide application, especially for the coating of red blood cells (RBC) with glutaraldehyde-polymerized human serum albumin (pHSA), for studies of the albumin receptor on hepatitis B surface antigen (HBsAg) or for the detection of anti-albumin antibodies (AAA). Here we report a previously unrecognized reactivity with glutaraldehyde-treated RBC mainly with sera from patients with liver disease. The highest incidences of this reaction were found in patients with acute viral hepatitis A and B, namely 44 of 50 (88%) and 31 of 50 (62%) respectively. In 234 HBsAg carriers the frequency was low (3%). This reactivity was also observed in 19 of 50 sera from patients with chronic liver disease documented by biopsy, but not in sera from 68 healthy subjects. By immunofluorescence on glutaraldehyde-treated RBC it was shown that the corresponding antibodies belonged mainly to the IgM class. In all HBsAg-negative patients studied the HA titer against glutaraldehyde-treated RBC was in agreement with the titer against RBC coated with pHSA or pBSA (polymerized bovine serum albumin). Absorption with pHSA abolished the reaction with glutaraldehyde-treated RBC in 7 of 8 sera, suggesting a common reactivity between glutaraldehyde-polymerized HSA and glutaraldehyde-treated RBC. Apart from the possible clinical importance of these antibodies, their existence is a possible source of false positive results when glutaraldehyde is used as a coupling reagent for immunological assays, in particular with sera from patients with liver diseases.