Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method

Caroline Wehmeier; Gonca E Karahan; Swiss Transplant Cohort Study; Juliette Krop; Yvonne de Vaal; Janneke Langerak-Langerak; Isabelle Binet; Stefan Schaub; Dave L Roelen; Frans H J Claas; Sebastiaan Heidt

doi:10.1097/TP.0000000000002909

Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method

Caroline Wehmeier
, Gonca E Karahan
, Swiss Transplant Cohort Study
, Juliette Krop
, Yvonne de Vaal
, Janneke Langerak-Langerak
, Isabelle Binet
, Stefan Schaub
, Dave L Roelen
, Frans H J Claas
, Sebastiaan Heidt^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

35 Citations (Scopus)

Abstract

BACKGROUND:

HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.

METHODS:

Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.

RESULTS:

Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).

CONCLUSIONS:

Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.

Original language	English
Pages (from-to)	1026-1032
Number of pages	7
Journal	Transplantation
Volume	104
Issue number	5
DOIs	https://doi.org/10.1097/TP.0000000000002909
Publication status	Published - May 2020
Externally published	Yes

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10.1097/TP.0000000000002909

Cite this

Wehmeier, C., Karahan, G. E., Swiss Transplant Cohort Study, Krop, J., de Vaal, Y., Langerak-Langerak, J., Binet, I., Schaub, S., Roelen, D. L., Claas, F. H. J., & Heidt, S. (2020). Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method. Transplantation, 104(5), 1026-1032. https://doi.org/10.1097/TP.0000000000002909

@article{1465c7a3488d427690b5d922c46821c3,

title = "Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method",

abstract = "BACKGROUND: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.METHODS: Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.RESULTS: Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45\%) patients and for 10 of 35 specificities (29\%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67\% vs 9\%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50\%) than nonpersisting DSA (2/16; 13\%).CONCLUSIONS: Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.",

author = "Caroline Wehmeier and Karahan, \{Gonca E\} and \{Swiss Transplant Cohort Study\} and Juliette Krop and \{de Vaal\}, Yvonne and Janneke Langerak-Langerak and Isabelle Binet and Stefan Schaub and Roelen, \{Dave L\} and Claas, \{Frans H J\} and Sebastiaan Heidt",

year = "2020",

month = may,

doi = "10.1097/TP.0000000000002909",

language = "English",

volume = "104",

pages = "1026--1032",

journal = "Transplantation",

issn = "0041-1337",

publisher = "Lippincott Williams \& Wilkins",

number = "5",

}

Wehmeier, C, Karahan, GE, Swiss Transplant Cohort Study, Krop, J, de Vaal, Y, Langerak-Langerak, J, Binet, I, Schaub, S, Roelen, DL, Claas, FHJ & Heidt, S 2020, 'Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method', Transplantation, vol. 104, no. 5, pp. 1026-1032. https://doi.org/10.1097/TP.0000000000002909

TY - JOUR

T1 - Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients

T2 - First Clinical Application of a Novel Method

AU - Wehmeier, Caroline

AU - Karahan, Gonca E

AU - Swiss Transplant Cohort Study

AU - Krop, Juliette

AU - de Vaal, Yvonne

AU - Langerak-Langerak, Janneke

AU - Binet, Isabelle

AU - Schaub, Stefan

AU - Roelen, Dave L

AU - Claas, Frans H J

AU - Heidt, Sebastiaan

PY - 2020/5

Y1 - 2020/5

N2 - BACKGROUND: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.METHODS: Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.RESULTS: Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).CONCLUSIONS: Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.

AB - BACKGROUND: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.METHODS: Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.RESULTS: Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).CONCLUSIONS: Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.

U2 - 10.1097/TP.0000000000002909

DO - 10.1097/TP.0000000000002909

M3 - Article

C2 - 31397804

SN - 0041-1337

VL - 104

SP - 1026

EP - 1032

JO - Transplantation

JF - Transplantation

IS - 5

ER -

Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method

Abstract

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