Chung Wen Yuan, Pollard Cristina A, Stover Cordula, Naziruddin Bashoo, Kumar Rohan, Isherwood John, Issa Eyad, Levy Marlon F, Garcea Giuseppe, Dennison Ashley R
Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Ann Transl Med. 2020 Mar;8(5):170. doi: 10.21037/atm.2020.02.19.
Numerous factors influence pancreatic islet survival following auto-transplantation. Of these, the host immune response in the early peri-operative period is one of the most important. In this study we investigated the role of the mannose-binding lectin (MBL)-dependent pathway in a group of total pancreatectomy (TP) islet auto-transplantation (TPIAT) patients and classified them as competent or deficient in MBL activity. Complement pathway activities, MBL protein and inflammatory cytokine concentrations were evaluated from eleven pancreatic islet auto-transplant patients from two institutions.
Eleven patients from two institutions were prospectively recruited. Serum was screened at different time points for 29 different cytokines and compared according to their MBL deficient or competent status. Twelve patients from previous TPIAT patients also underwent screening of MBL pathway activity.
A total nine of twenty three patients (39%) were MBL pathway deficient. MCP-1, IL-7 and IL-1a concentrations were significantly lower in the MBL deficient cohort compared to the normal MBL group (P=0.0237, 0.0001 and 0.0051 respectively). IL-6 and IL-8 concentrations were significantly raised in the normal MBL group. MBL functional activity was lower in insulin-independent group compared to the insulin-dependent group.
Complement activation is an important, possibly damaging response during intra-portal islet infusion. MBL pathway deficiency appears common in this population and the cytokine response was attenuated in MBL pathway deficient patients. Therapeutic MBL pathway blockade during and following islet auto-transplantation (IAT) may improve islet survival and function and thereby clinical outcome.
胰腺自体移植后，有众多因素影响胰岛存活。其中，围手术期早期的宿主免疫反应是最重要的因素之一。在本研究中，我们调查了甘露糖结合凝集素（MBL）依赖途径在一组全胰切除术（TP）胰岛自体移植（TPIAT）患者中的作用，并将他们分为MBL活性正常或缺陷组。对来自两个机构的11例胰腺胰岛自体移植患者的补体途径活性、MBL蛋白和炎性细胞因子浓度进行了评估。
前瞻性招募了来自两个机构的11例患者。在不同时间点对血清进行29种不同细胞因子的筛查，并根据其MBL缺陷或正常状态进行比较。之前接受TPIAT的12例患者也进行了MBL途径活性筛查。
23例患者中有9例（39%）MBL途径缺陷。与正常MBL组相比，MBL缺陷组的MCP-1、IL-7和IL-1α浓度显著降低（分别为P = 0.0237、0.0001和0.0051）。正常MBL组的IL-6和IL-8浓度显著升高。与胰岛素依赖组相比，非胰岛素依赖组的MBL功能活性较低。
补体激活是门静脉内胰岛输注过程中一种重要的、可能具有损害性的反应。MBL途径缺陷在该人群中似乎很常见，且MBL途径缺陷患者的细胞因子反应减弱。在胰岛自体移植（IAT）期间及之后进行治疗性MBL途径阻断可能会改善胰岛存活和功能，从而改善临床结局。
