Different responses of human anti-HLA and anti-αgal antibody to long- term intravenous immunoglobulin therapy

L. Bühler, D. Pidwell, Robert Dowling, D. Newman, M. Awwad, D. K.C. Cooper

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose α1-3 galactose (αGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-αGal IgG. Levels of PRA, anti-αGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-αGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-αGal IgG, catabolism of anti-αGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-αGal IgG level it would be necessary to use IVIG depleted of this antibody.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalXenotransplantation
Volume6
Issue number3
DOIs
StatePublished - Aug 1 1999

Fingerprint

Passive Immunization
Intravenous Immunoglobulins
Anti-Idiotypic Antibodies
Galactose
Antibodies
Swine
Therapeutics
Isoantibodies
Organ Transplantation
Heart Transplantation
Serum
Heterografts
Immunoglobulins
Endothelial Cells
anti-IgG

All Science Journal Classification (ASJC) codes

  • Immunology
  • Transplantation

Cite this

Bühler, L. ; Pidwell, D. ; Dowling, Robert ; Newman, D. ; Awwad, M. ; Cooper, D. K.C. / Different responses of human anti-HLA and anti-αgal antibody to long- term intravenous immunoglobulin therapy. In: Xenotransplantation. 1999 ; Vol. 6, No. 3. pp. 181-186.
@article{8281b1c49e2e4966b7ce15ee15413b19,
title = "Different responses of human anti-HLA and anti-αgal antibody to long- term intravenous immunoglobulin therapy",
abstract = "Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose α1-3 galactose (αGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1{\%} of anti-αGal IgG. Levels of PRA, anti-αGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85{\%}, 53{\%}, 23{\%}, 19{\%} and 19{\%} (mean 39{\%}). Mean PRA fell by 66{\%} after 3 months of therapy (to a mean PRA of 14{\%}), and by 96{\%} after 6 months therapy (to a mean PRA of 2{\%}). Anti-αGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-αGal IgG, catabolism of anti-αGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-αGal IgG level it would be necessary to use IVIG depleted of this antibody.",
author = "L. B{\"u}hler and D. Pidwell and Robert Dowling and D. Newman and M. Awwad and Cooper, {D. K.C.}",
year = "1999",
month = "8",
day = "1",
doi = "10.1034/j.1399-3089.1999.00026.x",
language = "English (US)",
volume = "6",
pages = "181--186",
journal = "Xenotransplantation",
issn = "0908-665X",
publisher = "Wiley-Blackwell",
number = "3",

}

Different responses of human anti-HLA and anti-αgal antibody to long- term intravenous immunoglobulin therapy. / Bühler, L.; Pidwell, D.; Dowling, Robert; Newman, D.; Awwad, M.; Cooper, D. K.C.

In: Xenotransplantation, Vol. 6, No. 3, 01.08.1999, p. 181-186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Different responses of human anti-HLA and anti-αgal antibody to long- term intravenous immunoglobulin therapy

AU - Bühler, L.

AU - Pidwell, D.

AU - Dowling, Robert

AU - Newman, D.

AU - Awwad, M.

AU - Cooper, D. K.C.

PY - 1999/8/1

Y1 - 1999/8/1

N2 - Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose α1-3 galactose (αGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-αGal IgG. Levels of PRA, anti-αGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-αGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-αGal IgG, catabolism of anti-αGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-αGal IgG level it would be necessary to use IVIG depleted of this antibody.

AB - Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose α1-3 galactose (αGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-αGal IgG. Levels of PRA, anti-αGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-αGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-αGal IgG, catabolism of anti-αGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-αGal IgG level it would be necessary to use IVIG depleted of this antibody.

UR - http://www.scopus.com/inward/record.url?scp=2442733198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442733198&partnerID=8YFLogxK

U2 - 10.1034/j.1399-3089.1999.00026.x

DO - 10.1034/j.1399-3089.1999.00026.x

M3 - Article

C2 - 10503784

AN - SCOPUS:2442733198

VL - 6

SP - 181

EP - 186

JO - Xenotransplantation

JF - Xenotransplantation

SN - 0908-665X

IS - 3

ER -