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

Table 3 Summaries of reported literature on HLA-DQ typing and anti-HLA-DQ donor-specific antibody

Ref.	Journal/year	Study type and sample type	Objectives	Findings
Taylor et al[104]	Tissues Antigens/1987	Case report	—	B cell crossmatch positive due to IgG DSA against HLA-DQ did not affect graft function till 1 yr follow-up
Bushell et al[54]	Human Immunology/1989	Retrospective study of 25 HLA-DQ-mismatched but DR-matched patient	To study effect of HLA-DQ mismatch in HLA-DR-matched patients	No beneficial effect
Freedman et al[111]	Clinical Transplants/1997	Retrospective study of 12050 deceased 1st kidney transplant	To analyze the effect of HLA-DQ phenotype matching on renal allograft survival	Nonsignificant 3.0% reduction in graft failure (P = 0.38) was observed for each level of increasing HLA-DQ match when using the Cox regression model adjusted for recipient and donor race, age and sex, cold ischemia time, body mass index, cyclosporine A use, year of transplant, diabetes mellitus, HLA-A, HLA-B and HLA-DR match
Iniotaki-Theodoraki et al[108]	Transplantation/2003	Case–control study of 142 patients. Group A had 32 immediately post-transplant patients and group B had 110 sensitized patients who had failed grafts	To study humoral immune reactivity against HLA-DQ graft molecules in the early post transplantation period	No rejection or graft dysfunction in first 6 months
Duquesnoy and Marrari[29]	Transplant Immunology/2008	Retrospective analysis of 75 class-II-sensitized patients with different types of failed allografts including 60 kidney, 4 liver, 4 heart, 2 lung, 2 pancreas and 3 small bowel transplants	To describe the effect the donor-specific HLA class II epitope mismatching on antibody reactivity patterns	HLA-DQB and -DQA mismatches led to production of anti-HLA-DQB antibodies in 87% and HLA-DQA antibodies in 64%
Hartono et al[105]	Journal of Medical Case Reports/2009	Case report of a successful retransplant with pre-existing anti-HLA-DQ5 antibodies	—	Graft function good until 2 years without any deleterious effects
Tambur et al[110]	Transplantation/2010	Observational study of the sera of 104 patients	To identify HLA-DQ antibodies directed to patient’s own DQ or DQ chain linked to non-self DQ chains	7% of patients had anti -HLA-DQ antibodies against patient’s own DQ or DQ chain. 21% had antibodies to their own DQβ chain and 62% had antibodies to their own DQα chain
Kobayashi et al[109]	Human Immunology/2011	Observational study of 586 kidney transplant recipients	To know the impact of DSAs against HLA-DRB and -DQB on development of chronic AMR in high, moderate and low risk	Anti-HLA-DQB DSAs were not associated with chronic AMR in all immunological risk categories
Willicombe et al[56]	Transplantation/2012	Retrospective analysis of 505 kidney transplant recipients	The aim of this study was to establish the incidence and outcomes after the development of HLA-DQ DSAs	Patients with anti-HLA-DQ DSAs were at significant risk for AMR, transplant glomerulopathy, and allograft loss (P < 0.0001)
DeVos et al[57]	Kidney International/2012	Prospective analysis of retrospective data of 347 without pretransplant DSAs	To study development of de novo anti-HLA-DQ DSAs and its impact on patient and graft	78% of all DSAs were anti-HLA-DQ. No relation with rejection found. Mean creatinine and proteinuria higher in anti-HLA-DQ DSAs. Anti-HLA-DQ DSAs along with non-DQ DSAs led to reduced 3-yr survival
Freitas et al[115]	Transplantation/2013	Retrospective analysis of 284 transplant recipients	To study complement-binding characteristics of HLA-DQ DSAs	Anti-HLA-DQ DSAs and non-DQ DSAs caused more acute rejection (P = 0.0009), increased graft loss and reduced 5-yr survival. Acute rejection had more IgG1/IgG3 combination and C1q-binding antibodies (51%, P = 0.01; and 63%, P = 0.001)
Tambur et al[116]	Transplantation/2014	Clinical and translational research in 40 transplant recipients	To analyze eplet and epitope of HLA-DQ in immunologically naive patients before failed transplantation	10 HLA-DQA eplets or eplet combinations and 13 HLA-DQB eplets or combinations identified
Sapir-Pichhadze et al[112]	American Journal of Transplantation/2015	Case–control study of 156 kidney transplant recipients. Cases consisted of patients with transplant glomerulopathy and controls without transplant glomerulopathy	To assess risk of transplant glomerulopathy as a function of donor and recipient HLA-DR and HLA-DQ incompatibility at the eplet level	Logistic regression model showed increased odd of transplant glomerulopathy (OR = 2.84, 95%CI: 1.73-7.84) in 27-43 eplet mismatches and (OR = 4.62, 95%CI: 1.51-14.14)
Lim et al[74]	Clinical Journal of the American Society of Nephrology/2016	Retrospective observational data of 788 recipients followed for 2.2 years	To assess impact of HLA-DQ mismatches on rejection	Compared with 0 HLA-DQ mismatched kidneys, those who received 1 or 2 HLA-DQ mismatched had more rejections (P < 0.01), late rejections (P = 0.03), and AMR (P = 0.01)
Chowdhry et al[106]	Asian Journal of Transfusion Science/2019	Case report of de novo DSAs against HLA-DQ in a retransplant	—	Chronic AMR after 2 years
Liu et al[107]	Transplant Immunology/2022	Case report of DSA against HLA-DQA1	—	Mixed rejection after 2 years

AMR: Antibody-mediated rejection; DSA: Donor specific antibodies; HLA: Human leukocyte antigen; IgG: Immunoglobulin G; OR: Odds ratio.