TY - JOUR
T1 - Anticytotoxin-neutralizing antibodies in immune globulin preparations
T2 - Potential use in hemolytic-uremic syndrome
AU - Ashkenazi, Shal
AU - Cleary, Thomas G.
AU - Lopez, Eduardo
AU - Pickering, Larry K.
N1 - Funding Information:
The cause and pathogenesis of hemolytic-uremic syndrome were unclear for years, 1, 2 but recent data have resulted in better understanding of this entity? ,4 Primary (classic) HUS, the most common variety, appears mainly in infants Supported in part by a grant from the Thrasher Research Foundation. Presented in part at the annual meeting of the Society for Pediatric Research Washington, D.C., May 1988. Submitted for publication March 28, 1988; accepted July 1, 1988. Reprint requests: Larry K. Pickering, MD, University of Texas Medical School at Houston, 6431 Fannin St., Room t.724, Houston, TX 77025.
PY - 1988/12
Y1 - 1988/12
N2 - The pathogenesis of primary (classic) hemolytic-uremic syndrome (HUS) is thought to be related to cytotoxin-producing enteric pathogens such as Shigella dysenteriae serotype 1 and Escherichia coli serotypes 0157:H7 and 026:H11. The relevant cytotoxins include Shiga toxin and the closely related Shiga-like toxins (SLTs) produced by some E. coli strains. Intravenously administered immune globulin (IVIG) therapy has been reported to be beneficial in a few children with HUS. We therefore examined commercially available immune globulin preparations for the presence of anticytotoxin-neutralizing antibodies. Cytotoxicity and neutralization of the HUS-associated cytotoxins were quantitatively determined by means of a (3H)thymidine-labeled HeLa cell assay. The immune globulin preparations tested almost completely neutralized Shiga toxin (produced by S. dysenteriae 1) and SLT-I (produced by E. coli serotype 026:H11). Twofold dilutions of the preparations showed significant (p<0.01) neutralizing titers of 1:64 to 1:128. No significant neutralization (>20%) of SLT-II (produced by E. coli strain C600 (933W)) was noted. The IVIG preparation lost its inhibitory activity when passed through a protein A-Sepharose column, which bound immune globulin, indicating that its neutralizing effect is related to the antibody content. We also examined sera from 30 children without diarrhea or HUS; only one child had neutralizing titers against Shiga toxin (1:64) and SLT-I (1:128). Immune globulin preparations contain anticytotoxin-neutralizing antibodies, a finding that warrants further investigation of the therapeutic role of these preparations in early treatment of children with HUS related to Shiga toxin and SLT-I.
AB - The pathogenesis of primary (classic) hemolytic-uremic syndrome (HUS) is thought to be related to cytotoxin-producing enteric pathogens such as Shigella dysenteriae serotype 1 and Escherichia coli serotypes 0157:H7 and 026:H11. The relevant cytotoxins include Shiga toxin and the closely related Shiga-like toxins (SLTs) produced by some E. coli strains. Intravenously administered immune globulin (IVIG) therapy has been reported to be beneficial in a few children with HUS. We therefore examined commercially available immune globulin preparations for the presence of anticytotoxin-neutralizing antibodies. Cytotoxicity and neutralization of the HUS-associated cytotoxins were quantitatively determined by means of a (3H)thymidine-labeled HeLa cell assay. The immune globulin preparations tested almost completely neutralized Shiga toxin (produced by S. dysenteriae 1) and SLT-I (produced by E. coli serotype 026:H11). Twofold dilutions of the preparations showed significant (p<0.01) neutralizing titers of 1:64 to 1:128. No significant neutralization (>20%) of SLT-II (produced by E. coli strain C600 (933W)) was noted. The IVIG preparation lost its inhibitory activity when passed through a protein A-Sepharose column, which bound immune globulin, indicating that its neutralizing effect is related to the antibody content. We also examined sera from 30 children without diarrhea or HUS; only one child had neutralizing titers against Shiga toxin (1:64) and SLT-I (1:128). Immune globulin preparations contain anticytotoxin-neutralizing antibodies, a finding that warrants further investigation of the therapeutic role of these preparations in early treatment of children with HUS related to Shiga toxin and SLT-I.
UR - https://www.scopus.com/pages/publications/0024246644
U2 - 10.1016/S0022-3476(88)80572-9
DO - 10.1016/S0022-3476(88)80572-9
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 3057156
AN - SCOPUS:0024246644
SN - 0022-3476
VL - 113
SP - 1008
EP - 1014
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 6
ER -