捐贈者特異性人類白血球抗體(anti-HLA-Cw1)陽性之高風險腎臟移植 - 病例報告

施欣佑、王碩盟、闕士傑

國立台灣大學醫學院附設醫院泌尿部

High-risk Kidney Transplantation with Preformed Donor-specific anti-HLA-Cw1 Antibody - a case report

Hsin-Yo Shih, Shuo-Meng Wang, Jeff S. Chueh

Department of Urology, National Taiwan University Hospital,

College of Medicine, National Taiwan University, Taipei, Taiwan

Introduction:

High-risk kidney transplantation remained a challenging issue of concern due to higher risk of graft failure arising from underlying diseases or immunological status, including presensitization events and preformed anti-donor antibody ¹. In particular, preformed donor-specific antibody and its amount are associated with higher risk of graft rejection and reduced graft survival rate ². Common management strategies for high-risk kidney transplantation involve plasmapheresis and the use of desensitizing agents, such as intravenous immunoglobulin and rituximab. In this case report, we present a high-risk kidney transplantation case involving preformed donor-specific anti-HLA-Cw1 antibody.

Case presentation:

A 56-year-old woman with B positive blood type suffering from progressive chronic kidney disease since her teens presented to NTUH urology clinic for evaluation of kidney transplantation considering impending renal failure. Renal biopsy before showed only interstitial fibrosis and mesangial hypercellularity without correctable etiology or pathogenesis. Pre-transplantation evaluations, including infection and malignancy screening, cardiac function, vascular structure, all showed no contraindication, and HLA typing for her and her brother, the B positive blood type living donor, revealed just one mismatch of HLA-A and one mismatch of HLA-DR. 

However, cross-matching revealed an equivocal 1:1 37’C B cell reaction with median channel shift(MCS) of 1602, and flow panel reactive antibody(PRA) for anti-HLA antibodies showed significant class I antibody amount with mean fluorescent intensity (MFI) of 892, both suggesting a preformed anti-donor antibody. Donor-specific antibody(DSA) panel was checked, which revealed the presence of anti-HLA-Cw1 antibody, compatible to HLA typing of the donor, with MFI of 501. History of blood transfusion with packed RBC after prior renal biopsy was suspected to be the culprit.

High-risk kidney transplantation was considered, and 200mg of rituximab was given 1 month before transplantation. Double filtration plasmapheresis (DFPP) was given for 4 cycles since a week before transplantation, followed by intravenous immunoglobulin(IVIG) 24 grams each after the first 3 cycles of DFPP. Cross-matching before DFPP and IVIG showed an increasing 1:4 37’C B cell reaction with MCS of 11450, suspecting false positive effect by rituximab. Following cross-matching a day before transplantation showed a decreasing 1:1 37’C B cell reaction with MCS of 3925, while self-cross-matching, defined as recipient serum reaction to recipient lymphocyte, showed no viable lymphocyte. Tacrolimus 0.1mg/kay/day has been used since a day before transplantation, and 200mg of basiliximab was given at the day of transplantation. The living donor kidney transplantation was performed with Lich-Gregoir's method at graft ureter and bladder anastomosis. Immunosuppressants as tacrolimus and mycophenolate were kept, and her renal function remained stable with serum creatinine level around 1.0 mg/dl so far during follow-up.  

Discussion:

        Regardless of the fact that the significance of anti-HLA-Cw antibody is sometimes underestimated due to lack of investigation in the past, recent studies revealed that anti-HLA-Cw antibodies might lead to increased hyperacute rejection ³, acute rejection resulting from preformed antibody ⁴, and chronic rejection ⁵. A cohort of 199 sensitized kidney transplantation patients were analyzed by grouping them into patients with preformed anti-Cw/DP DSA, anti-A/B/DR/DQ DSA, and no DSA at all ⁶. The biopsy-proven acute rejection-free survival and graft survival rate of anti-HLA-Cw/DP was significantly lower than no DSA group, and as bad as anti-A/B/DR/DQ DSA group, indicating that donor-specific anti–HLA-Cw antibodies are as harmful as other DSAs. Eliminating anti-HLA-Cw antibodies for better graft survival, as in our case, might be of great significance.

On the contrary, a cohort of 1069 patients awaiting deceased donor kidney transplantation underwent screening for anti-HLA antibodies, and showed that anti-HLA-Cw antibody was found in 13% of them, and 56% of sensitizers ⁷. While compared to other class I anti-HLA antibodies, anti-HLA-Cw antibodies were significantly lower in prevalence and MFI values in sensitized patients ⁷. Among them, 8 patients who eventually received kidney transplantation presented with donor-specific anti-HLA-Cw antibodies, and only one of these patients expressed strong DSA with an MFI greater than 6000 (MFI 11,680) and positive cross-matching. All of these 8 patients received no plasmapheresis but desensitizing agent induction alone, such as basiliximab, anti-thymoglobulin, or IVIG, and none of them developed acute rejection. This suggested that DFPP might be optional in our case considering the relatively low MFI, while further studies are still required to decide the necessity of plasmapheresis in preformed anti-HLA-Cw antibodies. 

Last but not least, recent study revealed that targets of anti-HLA-Cw antibodies could be specified as denatured HLA-Cw and native HLA-Cw by using single antigen flow PRA with conventional beads and beads with diminished expression of denatured HLA ⁸. Anti-native-HLA-Cw antibodies, compared to anti-denatured-HLA-Cw antibodies, were more relevant to crossmatch ratio, acute and chronic antibody-mediated rejections, and lower graft survival. This enlightened that distinguishing anti-native-HLA-Cw from anti-denatured-HLA-Cw antibodies could grow in importance in the future, considering diminishing highly prevalent anti-denatured-HLA-Cw antibodies might have no clinical benefit. 

Conclusion:

        We present a case of high-risk kidney transplantation with preformed donor-specific anti-HLA-Cw antibody and positive cross-matching result, treated with plasmapheresis and desensitizing agent, including rituximab, basiliximab, and IVIG. Eliminating donor-specific anti-HLA-Cw antibodies is known to be beneficial to graft survival, while stratification of different approaches and discrimination of clinically important subtypes still require further study to elaborate. 

Reference:

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