Díaz Varela Inmaculada, Sánchez Mozo Pilar, Centeno Cortés Alberto, Alonso Blanco Clara, Valdés Cañedo Francisco
Instituto de Ciencias de la Salud, Universidad de A Coruña, A Coruña, Spain.
J Am Soc Nephrol. 2003 Oct;14(10):2677-83. doi: 10.1097/01.asn.0000088723.07259.cf.
Xenotransplantation is increasingly viewed as a promising way to alleviate the problem of patients who have alloreactive lymphocytotoxic antibodies and therefore tend to accumulate on the waiting list for renal transplantation. One barrier to xenotransplantation in these patients could be the hyperacute or acute vascular rejection as a result of preexisting anti-HLA antibodies that recognize swine leukocyte antigens. The cross-reactivity of sera from 98 patients with pig lymphocytes was studied by flow cytometry. After absorption of xenoreactive natural antibodies (XNA), isotype, class, and antibody specificity causing a positive cross-match (XM) were determined. For nonsensitized patients, all of the antibody binding to pig lymphocytes was due to XNA, which were removed by pig red blood cells absorption. In contrast, in sensitized patients, after removal of XNA, pig lymphocyte XM remained positive. There was no correlation between antibody binding to pig lymphocytes and Ig isotype (IgG or IgM) or HLA class-specific antibodies. For testing evidence that class II-specific antibodies were responsible for antibody binding to pig lymphocytes, HLA class I-specific antibodies were absorbed with pooled human platelets. It was confirmed that HLA class II-specific antibodies were responsible for the positive pig XM, but the strength of the positive XM was weaker than the strength caused by HLA class I-specific antibodies. Sera with multiple specificities (plurispecific sera) displayed a greater frequency of cross-reactivity with swine leukocyte antigens (P < 0.05). Seven of 11 highly immunized patients without cross-reactivity IgG with porcine lymphocytes showed positive XM before an IgM was used. The results demonstrate the cross-reactive nature of HLA antibodies and therefore point out the need to perform a prospective XM after absorption of XNA in presensitized individuals.
异种移植越来越被视为一种有前景的方法，可缓解那些具有同种异体反应性淋巴细胞毒性抗体、因此往往在肾移植等待名单上不断累积的患者所面临的问题。对于这些患者而言，异种移植的一个障碍可能是由于预先存在的可识别猪白细胞抗原的抗HLA抗体导致的超急性或急性血管排斥反应。通过流式细胞术研究了98例患者血清与猪淋巴细胞的交叉反应性。在吸收异种反应性天然抗体（XNA）后，确定引起阳性交叉配型（XM）的同种型、类别和抗体特异性。对于未致敏患者，所有与猪淋巴细胞结合的抗体均归因于XNA，这些抗体可通过猪红细胞吸收而去除。相比之下，在致敏患者中，去除XNA后，猪淋巴细胞XM仍为阳性。与猪淋巴细胞结合的抗体与Ig同种型（IgG或IgM）或HLA类别特异性抗体之间无相关性。为了测试II类特异性抗体是否是导致抗体与猪淋巴细胞结合的原因，用混合人血小板吸收HLA I类特异性抗体。证实HLA II类特异性抗体是导致猪XM阳性的原因，但阳性XM的强度弱于HLA I类特异性抗体所导致的强度。具有多种特异性的血清（多特异性血清）与猪白细胞抗原发生交叉反应的频率更高（P < 0.05）。11例对猪淋巴细胞无交叉反应性IgG的高度免疫患者中有7例在出现IgM之前XM呈阳性。结果证明了HLA抗体的交叉反应性，因此指出在预致敏个体中吸收XNA后需要进行前瞻性XM检测。
