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

Table 2 Summaries of reported literature on HLA-DP typing and anti-HLA donor-specific antibody

Ref.	Journal/year	Study type and sample type	Objectives	Findings
Rosenberg et al[49]	Human Immunology/1992	Retrospective study of 37 patients	To study the influence isolated HLA-DP mismatches between donors and recipients	No benefit was found
Pfeiffer et al[48]	Transplant International/1995	Retrospective analysis of sera from 505 patients	To study the frequency and impact on graft function of HLA-DP antibodies	HLA-DP antibodies were found in 7.3%, and those with prior antibodies who had retransplantation had no impact on graft function
Redondo-Pachón et al[83]	Transplant Immunology/2016	Retrospective analysis of 440 kidney transplant patients	To study the effect of antibodies against HLA-DP detected with solid-phase assays on graft survival after kidney transplantation	No effect of survival was found
Mytilineos et al[95]	Transplantation/1997	Retrospective study in which 3600 retrospective DNA typing was performed first and then repeated in 1300 deceased kidney transplant	To assess influence of HLA-DPB mismatches on kidney graft outcome	No effect on 1st transplant. In 2nd transplant, the 1-yr survival rate of transplants with no HLA-DPB mismatch was 83% ± 2%, which was significantly higher than grafts with 1 mismatch (76% ± 2%, P = 0.02) and that of 2 mismatches (73% ± 3%, P = 0.003)
Laux et al[96]	Transplantation/2003	Retrospective analysis of 1478 patients who received a cadaver kidney retransplant	To study the effect of HLA-DPB1 epitopes on graft outcome	< 2 epitope mismatches have better survival than three epitope mismatches (at 2 yr: 77.8% vs 65.8%, P = 0.0112)
Qiu et al[97]	Transplantation/2005	Multicenter brief report of 232 sera from 4 centers	To describe the frequency of HLA-DP antibodies found in 323 patients who had functioning and rejected renal allografts	The 5.1% of 138 patients with functioning grafts, and 19.5% of 185 patients with rejected grafts (P < 0.001) had anti HLA-DP antibodies
Samaniego et al[87]	Clinical Transplants/2006	Case report of AMR due to HLA-DP DSA	—	Anti-HLA-DP antibody led to HLA-C4d-positive AMR
Vaidya et al[88]	Human Immunology/2007	Cas report of positive B cell crossmatch in full match patient	—	A single HLA-DP allele mismatch (DPB1 0601) resulted in positive B cells
Goral et al[89]	Nephrology, Dialysis, Transplantation/2008	2 case reports. 1st case was sensitized due to retransplant, pregnancy and blood transfusion and 2nd case was sensitized by blood transfusion only	—	Both cases has mixed rejections (acute cellular and AMR) needing therapy. First case has rejection in 2 mo and second case on d 12
Thaunat et al[90]	Transplant Immunology/2009	Case report of chronic AMR due to anti HLA-DP and antibodies to nondonor-specific HLA-DP, which has same amino acid sequence	—	Anti HLA-DP antibodies resulted in chronic AMR and author recommended epitope matching instead of antigen matching
Singh et al[91]	Transplantation/2010	Case report of fully matched patient who has 3 failed transplants and rejection due to anti-HLA-DP antibody	—	Patient develop borderline cellular rejection and AMR after 2 wk. There was a mismatch at the HLA-DPA1 locus and pre- and post-transplant sera identified DSA against DPA1 0103
Billen et al[98]	Tissue Antigens/2010	Retrospective analysis of pre- and post-transplant sera for HLA-DP antibodies	To analyze the incidence of HLA-DP antibodies in renal patients	The 14% (48/338) had anti HLA-DP DSAs. The 23% of these had DSAs pretransplant and 77 had DSAs after transplant. All DSAs had a single mismatch at a hypervariable region in 80% of cases
Jolly et al[85]	American Journal of Transplantation/2012	2 case reports. Case 1 was sensitized and had 3rd transplant with mismatches only for HLA-C 15 and HLA-DPB1 01 with negative crossmatch. Case 2 was live unrelated transplant from wife with 1-2-1 HLA-A, HLA-B, HLA-DR mismatched graft, with an additional single mismatch at the DP locus with positive B cell crossmatch	—	Patient 1 had acute cellular rejection on d 3 and AMR at wk 4. Patient 2 had AMR on d 11
Callender et al[7]	Human Immunology/2012	Retrospective analysis of 650 renal patients on waiting list	To determine the frequency of HLA-DP-specific antibodies in presence and absence of crossreactive HLA-DR antibodies	42% were reactive for HLA-DP antibodies. 58 of these were negative for crossreactive HLA-DR antigens, and 16 had no class II antibodies other than anti-HLA-DP
Mierzejewska et al[84]	Human Immunology/2014	Case report of recipient who had 3rd transplant and was completely matched except at HLA-DPA1 and -DPB1	—	AMR at d 13 due to presence of C1q binding IgG1 DSA against donor HLA-DPA1 and -DPB1
Cippà et al[50]	Human Immunology/2014	Case report of de novo donor HLA-DP-specific antibodies in a nonsensitized patient	—	Late AMR due to anti-HLA-DPS
Hörmann et al[99]	Clinical Transplantation/2016	Retrospective analysis of 195 consecutive kidney transplant patients	To study incidence and impact of anti-HLA-DP antibodies in renal transplantation	81 (49%) patients had anti-HLA-DP antibodies. Around 64% (n = 52) of patients were positive in the pretransplant samples and 36% (n = 29) were positive post-transplant. Anti-HLA-DP antibody-positive patients had a higher rate of rejection (P = 0.01)
Thammanichanond et al[92]	Transplantation Proceedings/2018	Case report of acute AMR by de novo Anti-HLA-DPβ and -DPα antibodies after kidney transplantation	—	Developed acute cellular and AMR after 15 months
Nikaein et al[93]	Transplant Immunology/2018	Brief communication of 2 cases who received transplants, 1 from living unrelated and the other from deceased donors. Both cases had DSAs to HLA-DPB with MFI > 15000	—	Both developed AMR (acute humoral rejection)
Marie et al[94]	Transplantation Report/2021	Case report of kidney transplants in 3 highly sensitized individuals with significant sensitization with donor-directed HLA-DP antibody and had kidney transplants from donors after brain death with positive B cell flow cytometry crossmatch	—	Case 1 (retransplant) had transplant glomerulopathy after 2 yr. Case 2 had no events. Case 3 had retransplant and AMR on d 10
Thammanichanond et al[86]	BMC Nephrology/2022	Case report of acute AMR associated with preformed HLA-DPα and HLA-DPβ DSAs that were not detected before transplantation	—	AMR at d 15 (this was first transplant)
Seitz et al[100]	Kidney International Reports/2022	Retrospective case–control study of 23 patients	To study the effect of pre-existing isolated HLA-DP-DSAs on renal allograft outcomes	Pre-existing HLA-DP DSAs was risk factor for AMR on multivariate analysis (HR = 9.578, P = 0.012). Patients with HLA-DP DSAs had increased microvascular scores (P = 0.0346) and worse transplant glomerulopathy (P = 0.015) compared with the standard immunological risk group
Pan et al[101]	HLA/2023	Meta-analysis of 5 studies with 1166 kidney transplant patients	To study the impact of preformed and de novo HLA-DP antibodies after renal transplantation on graft loss and rejection	De novo HLA-DP antibodies after transplantation showed an increased risk of graft loss or acute rejection (OR = 3.6, 95%CI: 1.6–8.10, P = 0.002, I2 = 52%). Preformed anti-HLA-DP antibodies did not show any effect

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