Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients

Kwaku Marfo, Ming Ling, Yi Bao, Brant Calder, Bin Ye, Nicole A.M. Hayde, Stuart M. Greenstein, Javier Chapochnick-Friedman, Daniel Glicklich, Graciela De Boccardo, Milan Kinkhabwala, Enver Akalin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

BACKGROUND: We conducted a prospective cohort study in highly sensitized kidney transplant candidates with a calculated panel reactive antibody (cPRA) greater than 50% and on the deceased-donor waiting list for more than 5 years to investigate the effects of intravenous immunoglobulin (IVIG) and rituximab treatment. METHODS: Desensitization protocol included two doses of IVIG (2 g/kg, max 120 g each dose) and a single dose of rituximab (375 mg/m). Patients were followed up monthly by Luminex single antigen beads. Whole blood gene expression profiles were studied by Affymetrix Human 1.0 ST GeneChips before and after treatment. RESULTS: Forty patients were eligible for desensitization treatment. Thirteen of these patients agreed to participate, and 11 completed the treatment. After a mean follow-up of 334 ± 82 days, two desensitized patients (18%) received a kidney transplant compared with 14 patients (52%) in the nondesensitized group. Comparing with 14 patients who received transplants without any desensitization treatment, desensitized patients showed higher class I (99% vs. 80%) and class II (98% vs. 69%) cPRA levels and more unacceptable antigens (32 vs. 8). Desensitization treatment did not lead to any significant reduction in patients' class I and II cPRA levels and any change in the mean number of unacceptable antigens or their mean fluorescence intensity values. Whole blood gene expression analysis by microarrays demonstrated down-regulation of immunoglobulin and B-cell-associated transcripts after treatment. CONCLUSION: These results suggested that pretransplant desensitization with IVIG and rituximab was not successful in highly sensitized kidney transplant candidates with cPRA levels higher than 90%.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
JournalTransplantation
Volume94
Issue number4
DOIs
StatePublished - Aug 27 2012

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Intravenous Immunoglobulins
Transplants
Antibodies
Kidney
Antigens
Therapeutics
Waiting Lists
Rituximab
Microarray Analysis
Transcriptome
B-Lymphocytes
Cohort Studies
Down-Regulation
Fluorescence
Tissue Donors
Prospective Studies
Gene Expression

Keywords

  • Desensitization
  • Gene expression
  • Intravenous immunoglobulin
  • Microarrays
  • Rituximab

ASJC Scopus subject areas

  • Transplantation

Cite this

Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients. / Marfo, Kwaku; Ling, Ming; Bao, Yi; Calder, Brant; Ye, Bin; Hayde, Nicole A.M.; Greenstein, Stuart M.; Chapochnick-Friedman, Javier; Glicklich, Daniel; De Boccardo, Graciela; Kinkhabwala, Milan; Akalin, Enver.

In: Transplantation, Vol. 94, No. 4, 27.08.2012, p. 345-351.

Research output: Contribution to journalArticle

Marfo, Kwaku ; Ling, Ming ; Bao, Yi ; Calder, Brant ; Ye, Bin ; Hayde, Nicole A.M. ; Greenstein, Stuart M. ; Chapochnick-Friedman, Javier ; Glicklich, Daniel ; De Boccardo, Graciela ; Kinkhabwala, Milan ; Akalin, Enver. / Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients. In: Transplantation. 2012 ; Vol. 94, No. 4. pp. 345-351.
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abstract = "BACKGROUND: We conducted a prospective cohort study in highly sensitized kidney transplant candidates with a calculated panel reactive antibody (cPRA) greater than 50{\%} and on the deceased-donor waiting list for more than 5 years to investigate the effects of intravenous immunoglobulin (IVIG) and rituximab treatment. METHODS: Desensitization protocol included two doses of IVIG (2 g/kg, max 120 g each dose) and a single dose of rituximab (375 mg/m). Patients were followed up monthly by Luminex single antigen beads. Whole blood gene expression profiles were studied by Affymetrix Human 1.0 ST GeneChips before and after treatment. RESULTS: Forty patients were eligible for desensitization treatment. Thirteen of these patients agreed to participate, and 11 completed the treatment. After a mean follow-up of 334 ± 82 days, two desensitized patients (18{\%}) received a kidney transplant compared with 14 patients (52{\%}) in the nondesensitized group. Comparing with 14 patients who received transplants without any desensitization treatment, desensitized patients showed higher class I (99{\%} vs. 80{\%}) and class II (98{\%} vs. 69{\%}) cPRA levels and more unacceptable antigens (32 vs. 8). Desensitization treatment did not lead to any significant reduction in patients' class I and II cPRA levels and any change in the mean number of unacceptable antigens or their mean fluorescence intensity values. Whole blood gene expression analysis by microarrays demonstrated down-regulation of immunoglobulin and B-cell-associated transcripts after treatment. CONCLUSION: These results suggested that pretransplant desensitization with IVIG and rituximab was not successful in highly sensitized kidney transplant candidates with cPRA levels higher than 90{\%}.",
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T1 - Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients

AU - Marfo, Kwaku

AU - Ling, Ming

AU - Bao, Yi

AU - Calder, Brant

AU - Ye, Bin

AU - Hayde, Nicole A.M.

AU - Greenstein, Stuart M.

AU - Chapochnick-Friedman, Javier

AU - Glicklich, Daniel

AU - De Boccardo, Graciela

AU - Kinkhabwala, Milan

AU - Akalin, Enver

PY - 2012/8/27

Y1 - 2012/8/27

N2 - BACKGROUND: We conducted a prospective cohort study in highly sensitized kidney transplant candidates with a calculated panel reactive antibody (cPRA) greater than 50% and on the deceased-donor waiting list for more than 5 years to investigate the effects of intravenous immunoglobulin (IVIG) and rituximab treatment. METHODS: Desensitization protocol included two doses of IVIG (2 g/kg, max 120 g each dose) and a single dose of rituximab (375 mg/m). Patients were followed up monthly by Luminex single antigen beads. Whole blood gene expression profiles were studied by Affymetrix Human 1.0 ST GeneChips before and after treatment. RESULTS: Forty patients were eligible for desensitization treatment. Thirteen of these patients agreed to participate, and 11 completed the treatment. After a mean follow-up of 334 ± 82 days, two desensitized patients (18%) received a kidney transplant compared with 14 patients (52%) in the nondesensitized group. Comparing with 14 patients who received transplants without any desensitization treatment, desensitized patients showed higher class I (99% vs. 80%) and class II (98% vs. 69%) cPRA levels and more unacceptable antigens (32 vs. 8). Desensitization treatment did not lead to any significant reduction in patients' class I and II cPRA levels and any change in the mean number of unacceptable antigens or their mean fluorescence intensity values. Whole blood gene expression analysis by microarrays demonstrated down-regulation of immunoglobulin and B-cell-associated transcripts after treatment. CONCLUSION: These results suggested that pretransplant desensitization with IVIG and rituximab was not successful in highly sensitized kidney transplant candidates with cPRA levels higher than 90%.

AB - BACKGROUND: We conducted a prospective cohort study in highly sensitized kidney transplant candidates with a calculated panel reactive antibody (cPRA) greater than 50% and on the deceased-donor waiting list for more than 5 years to investigate the effects of intravenous immunoglobulin (IVIG) and rituximab treatment. METHODS: Desensitization protocol included two doses of IVIG (2 g/kg, max 120 g each dose) and a single dose of rituximab (375 mg/m). Patients were followed up monthly by Luminex single antigen beads. Whole blood gene expression profiles were studied by Affymetrix Human 1.0 ST GeneChips before and after treatment. RESULTS: Forty patients were eligible for desensitization treatment. Thirteen of these patients agreed to participate, and 11 completed the treatment. After a mean follow-up of 334 ± 82 days, two desensitized patients (18%) received a kidney transplant compared with 14 patients (52%) in the nondesensitized group. Comparing with 14 patients who received transplants without any desensitization treatment, desensitized patients showed higher class I (99% vs. 80%) and class II (98% vs. 69%) cPRA levels and more unacceptable antigens (32 vs. 8). Desensitization treatment did not lead to any significant reduction in patients' class I and II cPRA levels and any change in the mean number of unacceptable antigens or their mean fluorescence intensity values. Whole blood gene expression analysis by microarrays demonstrated down-regulation of immunoglobulin and B-cell-associated transcripts after treatment. CONCLUSION: These results suggested that pretransplant desensitization with IVIG and rituximab was not successful in highly sensitized kidney transplant candidates with cPRA levels higher than 90%.

KW - Desensitization

KW - Gene expression

KW - Intravenous immunoglobulin

KW - Microarrays

KW - Rituximab

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