Schuller Max, Pfeifer Verena, Kirsch Alexander H, Klötzer Konstantin A, Mooslechner Agnes A, Rosenkranz Alexander R, Stiegler Philipp, Schemmer Peter, Sourij Harald, Eller Philipp, Prietl Barbara, Eller Kathrin
Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria.
Front Med (Lausanne). 2022 Feb 2;9:818882. doi: 10.3389/fmed.2022.818882. eCollection 2022.
The COVID-19 pandemic has major implications on kidney transplant recipients (KTRs) since they show increased mortality due to impaired immune responses to SARS-CoV-2 infection and a reduced efficacy of SARS-CoV-2 vaccination. Surprisingly, dialysis patients have shown superior seroconversion rates after vaccination compared to KTRs. Therefore, we investigated peripheral blood B cell (BC) composition before and after kidney transplantation (KT) and aimed to screen the BC compartment to explain impaired antibody generation.
A total of 105 patients were recruited, and multicolor flow cytometric phenotyping of peripheral venous blood BC subpopulations was performed before and 1 year after KT. Complete follow-up was available for 71 individuals. Anti-SARS-CoV-2 antibodies were collected retrospectively and were available for 40 subjects, who had received two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273).
Overall, relative BC frequencies within lymphocytes decreased, and their absolute counts trended in the same direction 1 year after KT as compared to CKD G5 patients. Frequencies and absolute numbers of naïve BCs remained stable. Frequencies of double negative BCs, a heterogeneous subpopulation of antigen experienced BCs lacking CD27 expression, were increased after KT, yet their absolute counts were similar at both time points. Transitional BCs (TrBCs) and plasmablasts were significantly reduced after KT in absolute and relative terms. Memory BCs were affected differently since class-switched and IgM-only subsets decreased after KT, but unswitched and IgD-only memory BCs remained unchanged. CD86 and CD5 expression on BCs was downregulated after KT. Correlational analysis revealed that TrBCs were the only subset to correlate with titer levels after SARS-CoV-2 vaccination. Responders showed higher TrBCs, both absolute and relative, than non-responders.
Together, after 1 year, KTRs showed persistent and profound compositional changes within the BC compartment. Low TrBCs, 1 year after KT, may account for the low serological response to SARS-CoV-2 vaccination in KTRs compared to dialysis patients. Our findings need confirmation in further studies as they may guide vaccination strategies.
2019年冠状病毒病（COVID-19）大流行对肾移植受者（KTRs）具有重大影响，因为他们对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的免疫反应受损，导致死亡率增加，且SARS-CoV-2疫苗接种效果降低。令人惊讶的是，与KTRs相比，透析患者在接种疫苗后显示出更高的血清转化率。因此，我们研究了肾移植（KT）前后外周血B细胞（BC）的组成，旨在筛查BC区室以解释抗体产生受损的原因。
共招募了105名患者，在KT前和KT后1年对外周静脉血BC亚群进行多色流式细胞术表型分析。71名个体有完整的随访数据。回顾性收集抗SARS-CoV-2抗体，40名接受两剂基于mRNA的疫苗（BNT162b2或mRNA-1273）的受试者有相关数据。
总体而言，与慢性肾脏病5期（CKD G5）患者相比，KT后1年淋巴细胞内BC的相对频率降低，其绝对计数也呈相同趋势。幼稚BC的频率和绝对数量保持稳定。双阴性BC是缺乏CD27表达的抗原经历BC的异质性亚群，其频率在KT后增加，但其绝对计数在两个时间点相似。过渡性BC（TrBC）和成浆细胞在KT后的绝对和相对数量均显著减少。记忆BC受到的影响不同，因为类别转换和仅IgM的亚群在KT后减少，但未转换和仅IgD的记忆BC保持不变。KT后BC上的CD86和CD5表达下调。相关性分析显示，TrBC是唯一与SARS-CoV-2疫苗接种后滴度水平相关的亚群。应答者的TrBC绝对和相对数量均高于无应答者。
总体而言，1年后，KTRs的BC区室显示出持续且深刻的组成变化。KT后1年TrBC数量低可能是KTRs与透析患者相比对SARS-CoV-2疫苗血清学反应低的原因。我们的发现需要进一步研究证实，因为它们可能指导疫苗接种策略。
