Donor human leukocyte antigen specific antibodies predict development and define prognosis in transplant glomerulopathy

Eng, Hooi Sian; Bennett, Greg; Chang, Sean; Dent, Hannah; McDonald, S.; Bardy, Peter; Coghlan, Patrick; Russ, Graeme R.; Coates, P. Toby

doi:10.1016/j.humimm.2011.02.002

Cited by 35 publications

(39 citation statements)

References 26 publications

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“…The incidence of graft failure in patients without DSAs, with DSAs directed against a single UCB unit (n ϭ 11), or with DSAs directed against both UCB units (n ϭ 7) was 5.5%, 18.2%, and 57.1%, respectively (Cochran-Armitage trend test, P ϭ .0001; Figure 1). Individual odds ratios (ORs) for graft failure comparing patients with DSAs against one UCB unit, DSAs against one or both UCB units, or DSAs against both UCB units to patients without DSAs were 3.85 (95% confidence interval [CI], 0.56%-26.4%; P ϭ .19), 8.67 (95% CI, 1.89%-39.68%; P ϭ .0055), and 23.1 (95% CI, 3.5%-153.9%; P ϭ .002), respectively. These statistical associations were maintained when patients who underwent reduced intensity conditioning (n ϭ 53) were examined.…”

Section: Graft Failurementioning

confidence: 99%

“…7 In solid organ transplantation, where crossing HLA barriers is routine, anti-HLA antibodies are linked to organ rejection and inferior outcomes. 8,9 In hematopoietic stem cell transplantation, more limited data exist on the significance of these antibodies. Spellman et al, in a retrospective case-control study, demonstrated that the prevalence of donor-specific anti-HLA antibodies (DSAs) was higher in a group of mismatched unrelated donor recipients who suffered graft rejection than in a control group that engrafted.…”

Section: Introductionmentioning

confidence: 99%

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Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation

Cutler¹,

Kim

Sun

et al. 2011

Blood

178

144

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Using a uniform detection method for donorspecific anti-HLA antibodies (DSAs), we sought to determine the effect of preformed DSAs on outcomes in double umbilical cord blood transplantation. DSAs were associated with an increased incidence of graft failure (5.5% vs 18.2% vs 57.1% for none, single, or dual DSA positivity; P ‫؍‬ .0001), prolongation of the time to neutrophil engraftment (21 vs 29 days for none vs any DSA; P ‫؍‬ .04), and excess 100-day mortality or relapse (23.6% vs 36.4% vs 71.4% for none, single, or dual DSA positivity; P ‫؍‬ .01). The intensity of DSA reactivity was correlated with graft failure (median of mean fluorescent intensity 17 650 vs 1 850; P ‫؍‬ .039). There was inferior long-term progression-free and overall survival when comparing patients with DSAs against both umbilical cord blood units to those without DSAs (3-year progression-free survival, 0% vs 33.5%, P ‫؍‬ .004; 3-year overall survival 0% vs 45.0%, P ‫؍‬ .04). We conclude that identification of preformed DSAs in umbilical cord blood recipients should be performed and that the use of umbilical cord blood units where preformed host DSAs exist should be avoided. (Blood. 2011; 118(25):6691-6697)

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Section: Graft Failurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation

Cutler¹,

Kim

Sun

et al. 2011

Blood

178

144

View full text Add to dashboard Cite

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“…TG develops as a consequence of overt and covert episodes of antibody-mediated rejection (5,(18)(19)(20)(21)(22)(23)(24), typically, due to HLA class II anti-HLA antibodies (5,10,(25)(26)(27)(28)(29)(30). Antibodies against HLA develop when antibody-accessible polymorphic residues on HLA antigens are recognized as ''nonself.''…”

Section: Introductionmentioning

confidence: 99%

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Sapir‐Pichhadze

Tinckam

Quach

et al. 2015

American Journal of Transplantation

116

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We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n ¼ 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n ¼ 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR þ DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR þ DQ eplet mismatches. Our study suggests that minimization of HLA-DR þ DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.

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“…The presence of high levels of class I and/or II DSA (i.e. anti-HLA antibodies with reactivity against the potential donor leading to positive complement-dependent cytotoxicity [CDC] cross-match) is associated with poorer graft outcomes, including the development of acute and chronic AMR, transplant glomerulopathy and late graft loss (Eng, Bennett et al 2008;Gloor, Winters et al 2010;Eng, Bennett et al 2011;Mujtaba, Goggins et al 2011). A study by LeFaucheur et al demonstrated that the presence of DSA significantly reduces graft survival rates compared to recipients without DSA (1 year graft survival -81% and 94% respectively and 8 years graft survival 47% and 78% respectively) (Lefaucheur, Suberbielle-Boissel et al 2008) ( Table 2).…”

Section: Desensitization Of Highly-sensitized Patients For Live-donormentioning

confidence: 99%

The Impact of Donor Type and Quality on Renal Transplant Outcomes

Nguyen¹,

Yong²,

Croke³

et al. 2011

Understanding the Complexities of Kidney Transplantation

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Donor human leukocyte antigen specific antibodies predict development and define prognosis in transplant glomerulopathy

Cited by 35 publications

References 26 publications

Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation

Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

The Impact of Donor Type and Quality on Renal Transplant Outcomes

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