Donor-specific antibodies against HLA-C, HLA-DP and HLA-DQ and their implications in kidney transplantation

Table 1 Summaries of reported literature on HLA-C typing and anti-HLA-C donor-specific antibody

Ref.	Journal/year	Study type and sample size	Objectives	Findings
Albrechtsen et al[75]	Transplantation Proceedings/1977	Retrospective: 142 living related 311 cadaveric transplants	To study influence of HLA on the outcome of kidney transplantation	No beneficial of HLA-C matching was found
Bryan et al[6]	Clinical Transplantation/2010	Retrospective: 60 sensitized patients	To describe frequency of HLA class I DSA	There was 42% positivity to HLA-Cw, which was significantly lesser than sensitization to HLA-A (80%) and HLA-B (83%)
Duquesnoy and Marrari[29]	Transplant Immunology/2011	Retrospective: Sera from 45 HLA-C mismatch after allograft nephrectomy	To detect antibodies against HLA-C epitopes in patients with rejected kidney transplants	HLA-C antibody frequencies and reactivities were lower than those induced by donor HLA-A and HLA-B mismatches
Ling et al[5]	Human Immunology/2012	Prospective observational: 1069 patients on waiting list	To determine prevalence and the strength of anti-HLA-Cw and -DP and effect on clinical outcome	Low prevalence and the strength of anti-HLA-Cw and HLA-DP as compared to others and patient and graft survival was 100% without rejection
Frohn et al[79]	Nephrology, Dialysis, Transplantation/2001	Retrospective analysis of 104 pairs analysis for HLA-C matching	To analyze if acute graft rejection is influenced by HLA-C matching	After exclusion of linkage disequilibrium, HLA-C mismatch was significantly associated with rejection (P = 0.004)
Chapman et al[30]	Transplantation/1986	Case report	—	Case report of hyperacute rejection in renal allograft recipient having HLA-Cw5 antibody
Baan et al[32]	Transplantation/1993	Case report of rejection in an unsensitized recipient of deceased kidney	—	Rejection was reported in HLA-C mismatched along with sublocus HLA-Bw22
Bachelet et al[31]	American Journal of Transplantation /2011	Case report of AMR in patient with immunoglobulin A nephropathy undergoing 3rd transplant	—	Anti-HLA-Cw DSA led to positive flow cytometry crossmatch and irreversible acute AMR
Gilbert et al[80]	Transplantation Proceedings/2011	Retrospective analysis of immunized recipients, (n = 176) had antibodies against only classical HLA antigens (A, B, DR and DQ) and 13.3% (n = 27) antibodies against HLA-C and/or HLA-DP	To determine whether the presence of specific HLA-C and HLA-DP antibodies before transplantation influenced graft outcomes in immunized recipients	DSA against HLA-C and HLA-DP along with DSAs against HLA-A, -AB, -DR and -DQ led to significant increase in the number of acute rejection episodes and graft loss due to immunological reasons
Suneja and Kuppachi[33]	Clinical Kidney Journal/2012	Case report of 21-yr-old transplant recipient who developed AMR after 21 mo of transplantation	—	DSA against HLA-Cw17 led to AMR
Aubert et al[9]	American Journal of Transplantation /2014	Retrospective case–control study of 608 renal transplant patients	To evaluate the clinical relevance of the presence of anti-HLA-C DSA at d 0	Incidence of AMR was significantly higher (27.3%) in patients with anti-HLA-C DSA and median MFI was 4966, which was significantly higher in AMR group
Bosch et al[76]	Human Immunology/2014	Case report of AMR in the second transplant	—	Patient had low MFI < 1000 in 1st transplant and has HLA-C mismatched second kidney and developed AMR on d 7
Bachelet et al[10]	Transplantation/2016	Comparative retrospective analysis of 199 who were divided in three groups for comparison	To analyze clinical impact of HLA-Cw/DP DSA by comparing with HLA-sensitized kidney transplant recipients with no DSA at d 0 and recipient with recipients with preformed HLA-A, HLA-B, HLA-DR and HLA-DQ DSAs	Positive flow cross match, 2-yr biopsy proven rejection were more in HLA-Cw/DP DSA and preformed HLA-A, -B, -DR and -DQ DSAs as compared to group with no DSAs and similarly less graft survival in HLA-Cw/DP DSAs and preformed HLA-A, -B, -DR and -DQ DSAs as compared to no DSAs
Santos et al[34]	World Journal of Transplantation/2016	Retrospective cohort study: 12 patients with anti HLA-Cw DSA and 23 with anti-HLA-A or HLA-B	To analyze the clinical impact of preformed anti-HLA-Cw vs anti-HLA-A and/or HLA-B DSAs in kidney transplantation	Similar risk of AMR (P = 1) and impact on graft function (P = 0.528) as compared to anti-HLA-A and/or HLA-B DSA
Persaud et al[77]	Human Immunology/2017	Case report of AMR in a living related transplant	—	Sensitization to HLA-Bw6 via exposure to paternal HLA-C14 during pregnancy likely predisposed this patient to AMR
Abuzeineh et al[78]	Clinical Nephrology Case Studies/2020	Case report of AMR in 39 yr old unsensitized patients	—	De novo DSAs against HLA-C led to AMR. Unexplained Fabry-like zebra bodies were also seen in biopsy
Visentin et al[82]	American Journal of Transplantation /2020	Retrospective observational study of 135 patients	To compare the pathogenicity of preformed anti-denatured and anti-native HLA-Cw antibodies in kidney transplant recipient	Anti-native HLA DSA had more acute and chronic AMR (P = 0.006 and P = 0.03, respectively), and had lower graft survival (P = 0.04)
Laboux et al[81]	Transplant International/2023	Retrospective multicentral observational study of 183 patients	To determinate risk factors of AMR in recipients transplanted with preformed isolated Cw-DSA or DP-DSA	The 12% in the HLA-Cw-DSA group, vs 28% in the HLA-DP DSA group had AMR. The increased risk associated with HLA-DP DSA compared with HLA-Cw DSA, was significant only for MFI < 3000

AMR: Antibody-mediated rejection; DSA: Donor specific antibody; HLA: Human leukocyte antigen; MFI: Mean florescence intensity.