Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
J Heart Lung Transplant. 2014 Nov;33(11):1149-56. doi: 10.1016/j.healun.2014.04.023. Epub 2014 May 9.
Most children transplanted with ABO-incompatible (ABOi) hearts develop selective tolerance to donor A/B antigens, whereas anti-A/B antibodies typically re-accumulate in adults after ABOi kidney transplantation. Deficiency of essential factors linking innate and adaptive immunity in early childhood may promote development of tolerance, specifically interactions between complement split product C3d and its ligand CD21 on B cells, considering their role in augmenting "T-independent" B-cell activation.
Blood and clinical data were analyzed from children after ABOi or ABO-compatible (ABOc) heart transplantation (HTx). Plasma C3d levels were quantified by enzyme-linked immunoassay. Peripheral blood mononuclear cells (PBMC) were phenotyped by flow cytometry; expression of B-cell co-receptor components CD21 and CD81 was quantified.
Fifty-five samples from pediatric HTx recipients (median age at transplant: 4.2 [range 0.03 to 20.4] months; age at sample collection: 14.6 [0.04 to 51.3] months; 53% ABOi) and 21 controls were studied. CD21-expressing B cells increased in trend with age (p = 0.079); longitudinal measures in individual patients showed a strong correlation with age. CD21 expression intensity in B-cells was not age-dependent. Plasma C3d levels did not correlate with age. Comparing ABOc vs ABOi HTx, CD21-expressing cell proportions were similar; however, serum C3d levels were significantly lower after ABOi HTx (p < 0.05).
In children, including HTx patients, CD21-expressing B-cells show a trend to increase with age, corresponding with improved responsiveness to polysaccharide antigens. This does not differ in patients with ABOi grafts developing tolerance to donor ABO antigens. C3d levels are not age-dependent, but reduced C3d levels after ABOi HTx suggest altered complement metabolism contributing to ABO tolerance.
大多数接受 ABO 不相容（ABOi）心脏移植的儿童会对供体 A/B 抗原产生选择性耐受，而在 ABOi 肾移植后，抗 A/B 抗体通常会在成人中重新积聚。在儿童早期，先天免疫和适应性免疫之间的必需因素缺失可能会促进耐受的发展，特别是补体分裂产物 C3d 与其在 B 细胞上的配体 CD21 之间的相互作用，因为它们在增强“T 细胞非依赖性”B 细胞激活方面发挥作用。
分析 ABOi 或 ABO 相容（ABOc）心脏移植（HTx）后儿童的血液和临床数据。通过酶联免疫吸附试验定量测定血浆 C3d 水平。通过流式细胞术对外周血单核细胞（PBMC）进行表型分析；定量测定 B 细胞共受体成分 CD21 和 CD81 的表达。
研究了 55 名儿科 HTx 受者（移植时的中位年龄：4.2[范围 0.03 至 20.4]个月；样本采集时的年龄：14.6[0.04 至 51.3]个月；53%ABOi）和 21 名对照者的 55 个样本。CD21 表达的 B 细胞随年龄呈增长趋势（p=0.079）；个体患者的纵向测量值与年龄具有很强的相关性。B 细胞中 CD21 表达强度与年龄无关。血浆 C3d 水平与年龄无关。ABOc 与 ABOi HTx 相比，CD21 表达细胞比例相似；然而，ABOi HTx 后血清 C3d 水平显著降低（p<0.05）。
在儿童中，包括 HTx 患者在内，CD21 表达的 B 细胞随年龄增长呈增长趋势，这与对多糖抗原的反应性提高相对应。在接受 ABO 供体抗原耐受的 ABOi 移植物患者中，这并没有差异。C3d 水平与年龄无关，但 ABOi HTx 后 C3d 水平降低提示补体代谢改变可能有助于 ABO 耐受。
