Dynamics of IgG Subclass as a Mechanism of Desensitization Using Rituximab for Presensitized Patients Undergoing Living Related Liver Transplantation

H. Egawa¹, K. Ide², T. Ishizuka³, H. Ohdan⁴, Y. Kotera¹, T. Kato¹, A. Ohmori¹, Y. Hirata¹, G. Shibuya¹, S. Yamashita¹, S. Ariizumi¹

¹Tokyo Women's Medical University, Tokyo, Japan, ²Surgery, Hiroshima University, Hiroshima, Japan, ³Clinical Laboratory, Tokyo Women's Medical University, Tokyo, Japan, ⁴Hiroshima University, Hiroshima, Japan

Meeting: 2021 American Transplant Congress

Abstract number: 1096

Keywords: Histocompatibility, HLA antibodies, Immunoglobulins (Ig), Liver transplantation

Topic: Clinical Science » Liver » Liver: Immunosuppression and Rejection

Session Information

Session Name: Liver: Immunosuppression and Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Although impact of preformed HLA-related donor specific antibody (DSA) and necessity of desensitization in liver transplantation (LT) has been recognized, mechanisms of desensitization in LT is not clarified yet.Aim: To examine mechanisms of desensitization for preformed DSA in living related liver transplantation (LDLT).

*Methods: Patients and Method: Six patients whose MFI of LABScreen single test of class 1 or class 2 DSA was greater than 10,000 underwent desensitization treatment using rituximab with a dose of 375 mg/m² 2 weeks before LDLT, whether cytotoxic direct crossmatch (CDC) is positive (n=3) or negative (n=3). As immunological assessments, CDC (T cell, B cell worm and B cell cold), flow crossmatch test (FCXM), flow PRA test, LABScreen single test for patients with positive PRA, and LABScreen complement test (C1q test) for positive CDC samples were examined. Further, IgG subclass analysis was added to 3 patients (#1, #2, #3) whose CDC turned to negative. The minimum follow-up period was 560 days after LT.

*Results: Results: The value of T cell/B cell CDC was 100%/100% in #1 and #3, and 0%/100% of #2. In #1, T cell CDC turned 0% after POD 3. B cell CDC (warm/cold) was remained 100%/100% until POD 64, 30%/0% on POD114 and 0%/0% on POD 900. FCXM-IgG turned to negative on POD114 but remained positive on POD900. Single bead MFI of DSA (A33, B44, B51, DR13, DR14) was over 10,000 before LT and decreased with fluctuation after LT and 0, 3,916, 8,457, 2,932, and 2,847 on POD 900, respectively. MFI of C1q test turned to 0 on POD 3. IgG subclass analysis showed persistent domination of IgG1 in A33, B44, B51 DSAs and switching from IgG1 dominant to IgG2 dominant after LT in DR13 and DR14 DSAs. On the other hand, values of CDC, FCXM-IgG, single bead MFI and C1q test changed harmonically and IgG subclass was IgG1 dominant in #2 and #3.

*Conclusions: Discussion: In #1, Subclass switch from IgG1 from IgG2 could contribute to diminishing of complement activation of Class 2 DSA, while decrease of total amount of antibody with dominance of IgG1 could contribute in class 1 DSA of #1 and class 1 and 2 in #2 and #3.Conclusion: Subclass dynamism could be a possible mechanism of desensitization.

To cite this abstract in AMA style:

Egawa H, Ide K, Ishizuka T, Ohdan H, Kotera Y, Kato T, Ohmori A, Hirata Y, Shibuya G, Yamashita S, Ariizumi S. Dynamics of IgG Subclass as a Mechanism of Desensitization Using Rituximab for Presensitized Patients Undergoing Living Related Liver Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/dynamics-of-igg-subclass-as-a-mechanism-of-desensitization-using-rituximab-for-presensitized-patients-undergoing-living-related-liver-transplantation/. Accessed November 21, 2024.

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