Early diagnosis of antibody-related rejection after kidney transplantation

Establishment of technology to detect IgM/IgG type anti-donor HLA antibodies from peripheral blood B cells

Advantages

  • Treatment guidelines, such as increasing the dose of immunosuppressive drugs to improve transplant organ survival, can be determined early after transplantation.
  • Enables early diagnosis with higher detection sensitivity than existing anti-donor HLA antibody (Donor Specific Antibody; DSA) serum tests.

Background and Technology

 In the United States, more than 10,000 kidney transplants are performed annually, but the 10-year survival rate after kidney transplantation is only 40%-60%. Since antibody mediated rejection (ABMR) is a major cause of failure, ABMR diagnosis by monitoring DSA in serum has been proposed. However, accurate prediction and early detection of ABMR by DSB monitoring has been difficult because DSA is mainly adsorbed by the graft after transplantation and is present in only a small proportion of serum.

 The inventors succeeded in detecting IgM/IgG-type DSA in the culture supernatant of peripheral blood-derived B cells, which were differentiated and cultured from memory B cells to plasma cells in vitro. Furthermore, we found that the pattern of IgM/IgG detection in the culture supernatant was different between ABMR patients and recipients who had stable survival after transplantation. The test using this technology is expected to be useful in guiding treatment such as dose increase and early discontinuation of immunosuppressive drugs.

Data

Peripheral blood mononuclear cells from 16 transplant kidney recipients with stable graft function or ABMR were de novo sensitized with donor-specific antigens and cultured in vitro for 1 week. Subsequent comparison of IgG and IgM HLA antibody levels (%) in the culture supernatant showed a significant difference in relation to graft function stability.

Researchers

Yoshiko Matsuda and Shiro Takahara

Patent & Publications

WO2018/117011 US2020/0174014

Yoshiko Matsuda et. al. Evaluation of antigen-specific igM and igg Production during an In Vitro Peripheral Blood Mononuclear cell culture assay. Frontiers in Immunology July 2017 | Volume 8 | Article 794  

Product No.JT-01663

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