Infusion of high-dose intravenous immunoglobulin fails to lower the strength of human leukocyte antigen antibodies in highly sensitized patients

Nada Alachkar, Bonnie E. Lonze, Andrea A. Zachary, Mary J. Holechek, Karl Schillinger, Andrew M Cameron, Niraj M Desai, Nabil N. Dagher, Dorry Segev, Robert A. Montgomery, Andrew L. Singer

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalTransplantation
Volume94
Issue number2
DOIs
StatePublished - Jul 27 2012

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Intravenous Immunoglobulins
HLA Antigens
Transplantation
Antibodies
Tissue Donors
Therapeutics
Blood Group Antigens
Serum
Intravenous Infusions
Kidney Transplantation
Allografts
Kidney

Keywords

  • Desensitization
  • Intravenous immunoglobulin
  • Kidney transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Infusion of high-dose intravenous immunoglobulin fails to lower the strength of human leukocyte antigen antibodies in highly sensitized patients. / Alachkar, Nada; Lonze, Bonnie E.; Zachary, Andrea A.; Holechek, Mary J.; Schillinger, Karl; Cameron, Andrew M; Desai, Niraj M; Dagher, Nabil N.; Segev, Dorry; Montgomery, Robert A.; Singer, Andrew L.

In: Transplantation, Vol. 94, No. 2, 27.07.2012, p. 165-171.

Research output: Contribution to journalArticle

Alachkar, Nada ; Lonze, Bonnie E. ; Zachary, Andrea A. ; Holechek, Mary J. ; Schillinger, Karl ; Cameron, Andrew M ; Desai, Niraj M ; Dagher, Nabil N. ; Segev, Dorry ; Montgomery, Robert A. ; Singer, Andrew L. / Infusion of high-dose intravenous immunoglobulin fails to lower the strength of human leukocyte antigen antibodies in highly sensitized patients. In: Transplantation. 2012 ; Vol. 94, No. 2. pp. 165-171.
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abstract = "BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100{\%} and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8{\%} of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41{\%} of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.",
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AU - Alachkar, Nada

AU - Lonze, Bonnie E.

AU - Zachary, Andrea A.

AU - Holechek, Mary J.

AU - Schillinger, Karl

AU - Cameron, Andrew M

AU - Desai, Niraj M

AU - Dagher, Nabil N.

AU - Segev, Dorry

AU - Montgomery, Robert A.

AU - Singer, Andrew L.

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N2 - BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.

AB - BACKGROUND: Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). METHODS: We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. RESULTS: Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. CONCLUSIONS: This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.

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