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Abstract: Anti-human histocompatibility antigen antibodies (HLA-Ab) are deleterious after kidney transplant and may be increased after T-cell depleting agents are given. A retrospective case control study was conducted to evaluate increase in HLA-Ab in 27 kidney transplant recipients who had received antithymocyte globulin (ATG) induction compared with 27 control subjects. A greater than 10% increase in class I or class II HLA-Ab was found in 6 (22.2%) of ATG subjects versus only 1 (3.7%) of non-ATG subjects (p = 0.05). In females, 6/14 ATG subjects developed increased HLA-Ab ≥10% compared with none of the control subjects (p = 0.016). In sensitized subjects, 4/10 in the ATG group developed increased HLA-Ab ≥10% versus none of the controls (p = 0.043). There was no difference in number or severity of acute rejection episodes or estimated glomerular filtration rate 6 months after transplant between the two treatment groups. We conclude that ATG induction may result in increased posttransplant HLA-Ab, particularly in subjects at higher immunologic risk. Further studies are necessary to determine the natural history, clinical consequences, appropriate therapy, and mechanisms responsible for HLA-Ab in this setting. [Copyright &y& Elsevier]

Aim Bw4 and Bw6 are mutually exclusive HLA Class I “public” epitopes encoded by amino acids 77–83. We sought to explore selective reactivity patterns of sera with antigens which only differed for Bw4 or Bw6. Methods We tested 6726 sera from 2953 transplant candidates using Labscreen ® Single Antigen (One Lambda, Canoga Park, CA). We focused on target alleles B ∗ 27:05(Bw4) vs B ∗ 27:08(Bw6) and B ∗ 53:01(Bw4) vs B ∗ 35:01(Bw6). Reactions were called Positive (MFI > 3000) or Negative (MFI < 1000) and a correlation table constructed on the combinations of bead reactivity. The sera which had anti-Bw4 or anti-Bw6 based on selective reactivity within the above allele pairs were examined for reactivity with the other 96 assay beads bearing either Bw4 or Bw6. Results Table 1 shows the excellent correlation between the two sets of allele pairs we used to detect anti-Bw4/Bw6 antibody. Fig. 1 shows that the mean MFI against Bw4 or Bw6 on the other target alleles in the kit were strongly predicted based only on the deduction from the two B27 alleles. Similar predictive value was found for the B35/B53 allele pair. Conclusion Use of selective reactivity of sera with allele targets which only differ in the Bw4 or Bw6 epitopes is a definitive method for detecting such antibodies without presence of masking antibodies against private antigens. Table 1 Bw4 Bw6 B ∗ 53:01posB ∗ 35:01neg B ∗ 53:01negB ∗ 35:01pos Bw4 B ∗ 27:05posB ∗ 27:08neg 79 0 Bw6 B ∗ 27:05negB ∗ 27:08pos 1 37 [ABSTRACT FROM AUTHOR]

HLA matching and avoidance of pre-transplant donor-specific antibodies are important in selection of donors for solid organ transplant. Solid phase testing with single antigen beads allows resolution of antibody reactivity to the level of the allele. Single antigen bead testing results at a large transplant center were reviewed to identify selective reactivity patterns of anti-HLA antibodies. Many HLA-DP antibodies were identified in the context of other HLA antibodies, but some sera had antibodies against only HLA-DP. B cell flow crossmatch testing was positive for 2 out of 9 sera with HLA-DP antibodies. Many patterns of reactivity corresponded to epitopes in hypervariable regions C and F of DPB1, but some matched epitopes in other regions or DPA1. Through analysis of single antigen bead testing from a large number of patients, we report that anti-HLA-DP antibodies predominantly recognize broadly cross-reactive epitopes. The United Network for Organ Sharing has mandated HLA-DP typing on all deceased kidney donors, and HLA-DP epitopes should be considered as the major antigens for avoidance of pre-transplant donor-specific antibodies. [ABSTRACT FROM AUTHOR]

Aim Accurate classification of serologically-distinct antigens (Ag) is critical in organ allocation, and nowadays it is possible to define anti-HLA antibody specificity to the allelic level. We examined class I antibodies (Ab) for allelic specificities that may be serologically distinct and evaluated its impact on crossmatch (XM) results and organ allocation. Methods 6726 sera were tested for anti-HLA Ab using LABScreen Single Ag assay (One Lambda), in which 17 class I HLA Ag are represented by more than one allele. Discordance in MFI values between the two allelic beads was examined as a categorical variable to mimic clinical practice, and as a continuous variable (MFI value) to better reflect biological plausibility. To evaluate the significance of an allele-specific Ab on XM results, we examined an unbiased cohort of deceased donor-candidate testing (125,828 CDC XMs between 2014 and 2017). In our lab, all candidates within a blood group have a CDC XM performed, regardless of whether they have donor-specific antibody (DSA). This uniquely allows us to examine whether a candidate with an allele-specific DSA, who has already been excluded from the match run, would indeed have a positive XM against a donor who has a different allele. Statistical analyses were performed using JMP12Pro (SAS Institute). Results 1. The incidence of discordance between the two allelic beads varied depending on whether MFI values were considered as continuous vs categorical variables. 2. The presence of allele-specific Ab for rare alleles was out of proportion to their frequencies in the population. 3. The presence of Ab against only the rare allele was a poor predictor of a positive CDC XM, with a positive predictive value of 0–7% compared with 52.5% if the candidate had DSA against an A or B locus Ag. Conclusions 9 out of 17 Class I HLA antigens had potential allele-specific reactivity, meaning that candidates with antibody selectivity against rare alleles may be unnecessarily excluded from many organ offers based on definition of unacceptable antigens by serological equivalence. Conversely, for centers relying on virtual-XM, prematurely defining alleles as new serological splits could unfortunately allow transplants for which the recipient has DSA. Further testing is needed to rigorously confirm these allele-specific reactivity patterns. [ABSTRACT FROM AUTHOR]