Clinical relevance of HLA-specific memory B cells in kidney transplant recipients undergoing desensitization

Clinical relevance of HLA-specific memory B cells in kidney transplant recipients undergoing desensitization - Donor-sepcific memory B cells in kidney transplantation.

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON49890

Enrollment

Registered

2021-12-23

Start date

2022-01-12

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

niertransplantatatie immunization kidney transplantation

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - Adult kidney transplant recipients (>=18 years of age) receiving a kidney transplantation in the Erasmus Medical Center - Adult kidney transplant recipients who are HLA-incompatible with their kidney donor, and who are defined as: -either participating in the national referral program for desensitization for HLA-incompatible living-donor kidney transplantation -or receiving an HLA-incompatible deceased-donor via the Imlifidase desensitization protocol - able to give written informed consent

Exclusion criteria

Exclusion criteria: - below 18 years of age - unable to give written informed consent - previous treatment with Rituximab (CD20 monoclonal antibody) or any other B-cell depleting therapy during the last 12 months.

Design outcomes

Primary

Measure	Time frame
Main study parameter is to determine whether HLA-specific memory B cells are present and underlying the serum HLA-specific antibody rebound and/or the persistence of the rebound in desensitized transplant recipients. The investigated endpoint will be the occurrence of serum donor-specific antibody rebound 3 months after transplantation.	—

Secondary

Measure	Time frame
1) To investigate the associations between the presence of IgG isotype of donor-specific memory (DSM) at the time of transplantation following desensitization with serum DSA rebound at month 3, month 6 and month 12 after transplantation. 2) To monitor whether IgM HLA-specific B-cell memory precedes IgG specific B-cell memory and IgG DSA formation, an HLA-specific IgM memory B-cell assay will be developed. IgM isotype of donor-specific B-cell memory will be compared with serum DSA formation. 3) In order to assess the evolution of donor-specific memory over time (IGM and IgG separately), donor-specific memory before desensitization and after desensitization will be compared to the presence or absence of donor-specific memory at month 3, month 6 and month 12 after transplantation. 4) To assess whether lymph node-residing HLA-specific memory B-cells and peripheral blood memory B-cells are independent variables, HLA-specific memory B-cell-derived antibody repertoire of peripheral blood at time of transplantation and intraoperatively dissected lymph nodes will be compared. 5) To determine whether changes in the frequency and phenotype of circulating B-cells as well as their differentiation status reflect the progression of the humoral alloimmune response, comprehensive immunophenotypic characterization of peripheral blood memory B-cells and plasma cells will be performed. 6) Associations between primary and secondary study parameters with biopsy proven ABMR within the first year after transplantation will be determined.	—

Measure

Time frame

1) To investigate the associations between the presence of IgG isotype of donor-specific memory (DSM) at the time of transplantation following desensitization with serum DSA rebound at month 3, month 6 and month 12 after transplantation. 2) To monitor whether IgM HLA-specific B-cell memory precedes IgG specific B-cell memory and IgG DSA formation, an HLA-specific IgM memory B-cell assay will be developed. IgM isotype of donor-specific B-cell memory will be compared with serum DSA formation. 3) In order to assess the evolution of donor-specific memory over time (IGM and IgG separately), donor-specific memory before desensitization and after desensitization will be compared to the presence or absence of donor-specific memory at month 3, month 6 and month 12 after transplantation. 4) To assess whether lymph node-residing HLA-specific memory B-cells and peripheral blood memory B-cells are independent variables, HLA-specific memory B-cell-derived antibody repertoire of peripheral blood at time of transplantation and intraoperatively dissected lymph nodes will be compared. 5) To determine whether changes in the frequency and phenotype of circulating B-cells as well as their differentiation status reflect the progression of the humoral alloimmune response, comprehensive immunophenotypic characterization of peripheral blood memory B-cells and plasma cells will be performed. 6) Associations between primary and secondary study parameters with biopsy proven ABMR within the first year after transplantation will be determined.

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Countries

Netherlands

Outcome results