Department of Nephrology, University Hospital, Birmingham, UK.
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Am J Transplant. 2021 Nov;21(11):3649-3662. doi: 10.1111/ajt.16712. Epub 2021 Jul 5.
ABO-incompatible (ABOi) transplantation requires preemptive antibody reduction; however, the relationship between antibody-mediated rejection (AMR) and ABO-antibodies, quantified by hemagglutination (HA), is inconsistent, possibly reflecting variable graft resistance to AMR or HA assay limitations. Using an ABH-glycan microarray, we quantified ABO-A antigen-subtype (A-subtype)-specific IgM and IgG in 53 ABO-O recipients of ABO-A kidneys, before and after antibody removal (therapeutic plasma exchange [TPE] or ABO-A-trisaccharide immunoadsorption [IA]) and 1-year posttransplant. IgM binding to all A-subtypes correlated highly (R ≥ .90) and A-subtype antibody specificities was reduced equally by IA versus TPE. IgG binding to the A-subtypes (II-IV) expressed in kidney correlated poorly (.27 ≤ R ≤ .69). Reduction of IgG specific to A-subtype-II was equivalent for IA and TPE, whereas IgG specific to A-subtypes-III/IV was not as greatly reduced by IA (p < .005). One-year posttransplant, IgG specific to A-II remained the most reduced antibody. Immunostaining revealed only A-II on vascular endothelium but A-subtypes II-III/IV on tubular epithelium. These results show that ABO-A-trisaccharide is sufficient for IgM binding to all A-subtypes; this is true for IgG binding to A-II, but not subtypes-III/IV, which exhibits varying degrees of specificity. We identify A-II as the major, but importantly not the sole, antigen relevant to treatment and immune modulation in adult ABO-A-incompatible kidney transplantation.
ABO 不相容（ABOi）移植需要抢先进行抗体减少；然而，通过血凝（HA）定量的抗体介导的排斥反应（AMR）与 ABO 抗体之间的关系不一致，这可能反映了移植物对 AMR 的不同抗性或 HA 检测的局限性。使用 ABH 聚糖微阵列，我们在 ABO-A 肾脏的 53 名 ABO-O 受者中，在抗体清除（治疗性血浆置换[TPE]或 ABO-A-三糖免疫吸附[IA]）前后以及移植后 1 年，定量了 ABO-A 抗原亚型（A 亚型）特异性 IgM 和 IgG。所有 A 亚型的 IgM 结合均高度相关（R≥.90），IA 与 TPE 对 A 亚型抗体特异性的减少程度相等。与肾脏中表达的 A 亚型（II-IV）的 IgG 结合相关性较差（.27≤R≤.69）。IA 和 TPE 对 A 亚型-II 特异性 IgG 的减少程度相同，而 IA 对 A 亚型-III/IV 特异性 IgG 的减少程度则不那么大（p<.005）。移植后 1 年，A-II 特异性 IgG 仍然是减少最多的抗体。免疫染色仅显示血管内皮上的 A-II，但在肾小管上皮上显示 A 亚型-II-III/IV。这些结果表明，ABO-A-三糖足以使所有 A 亚型的 IgM 结合；这对 A-II 的 IgG 结合是正确的，但对 A-III/IV 亚型则不正确，后者表现出不同程度的特异性。我们确定 A-II 是与成人 ABO-A 不相容性肾移植中治疗和免疫调节相关的主要但并非唯一的抗原。
