Naturally occurring immunoglobulin M (nIgM) autoantibodies prevent autoimmune diabetes and mitigate inflammation after transplantation.
Naturally occurring immunoglobulin M (nIgM) autoantibodies prevent autoimmune diabetes and mitigate inflammation after transplantation.
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DOI：
10.1097/sla.0b013e31826b4ba9
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发表时间：
2012-10
影响因子：
9
通讯作者：
Brayman KL
中科院分区：
文献类型：
--
作者：
Chhabra P;Schlegel K;Okusa MD;Lobo PI;Brayman KL
旨在研究多克隆血清天然免疫球蛋白 M (nIgM) 疗法是否可预防自身免疫性糖尿病的发作和进展并促进胰岛同种异体移植物的存活。 nIgM 缺乏与自身免疫性疾病发展趋势增加相关。 nIgM 抗白细胞自身抗体水平升高与移植排斥反应减少相关。 4 至 5 周龄雌性非肥胖糖尿病 (NOD) 同窝小鼠接受腹腔注射 nIgM 或磷酸盐缓冲盐水/牛血清白蛋白/免疫球蛋白 G（100 μg，随后每两周 50-75 μg）直至 18 周龄。 300 BALB/c 或 50 C57BL/6 胰岛移植物的 C57BL/6 受体接受盐水或 nIgM。接受盐水治疗的对照组小鼠 (n = 30) 中 80% 在 18 至 20 周龄时患上糖尿病。相比之下，33 只接受 nIgM 治疗的小鼠均未患糖尿病（P < 0.0001）。停药后 22 周，停药导致 33 只小鼠中只有 9 只出现高血糖，表明出现了 β 细胞无反应。在 11 周龄开始的 nIgM 治疗中，只有 20% 的治疗动物 (n = 20) 出现高血糖，而对照组的这一比例为 80% (P < 0.0001)。用nIgM（75 μg，每周3次）治疗轻度糖尿病小鼠可恢复正常血糖（n = 5），而严重糖尿病小鼠则需要用nIgM进行最小剂量的胰岛移植才能恢复正常血糖（n = 4）。链脲佐菌素诱导的糖尿病 C57BL/6 小鼠中移植的 BALB/c 胰岛移植物的平均存活时间，nIgM 治疗的受者（n = 4，第 5 个受者血糖保持正常）为 41.2 ± 3.3 天，而对照组（n = 5）为 10.2 ± 2.6 天（P < 0.001）。此外，同基因移植后，nIgM 治疗的受者 (n = 5) 恢复正常血糖所需时间为 15.4 ± 3.6 天，而对照组 (n = 4) 则需要超过 35 天。 nIgM 疗法显示出预防自身免疫性糖尿病的发病和进展以及促进胰岛移植物存活的潜力。
To investigate whether polyclonal serum naturally occurring immunoglobulin M (nIgM) therapy prevents the onset and progression of autoimmune diabetes and promotes islet allograft survival. nIgM deficiency is associated with an increased tendency toward autoimmune disease development. Elevated levels of nIgM anti-leukocyte autoantibodies are associated with fewer graft rejections. Four- to five-week-old female nonobese diabetic (NOD) littermates received intraperitoneal nIgM or phosphate-buffered saline/bovine serum albumin/immunoglobulin G (100 μg followed by 50–75 μg biweekly) until 18 weeks of age. C57BL/6 recipients of 300 BALB/c or 50 C57BL/6 islet grafts received saline or nIgM. Eighty percent control mice (n = 30) receiving saline became diabetic by 18 to 20 weeks of age. In contrast, none of 33 of nIgM-treated mice became diabetic (P < 0.0001). Discontinuing therapy resulted in hyperglycemia in only 9 of 33 mice at 22 weeks postdiscontinuation, indicating development of β-cell unresponsiveness. nIgM therapy initiated at 11 weeks of age resulted in hyperglycemia in only 20% of treated animals (n = 20) compared with 80% of controls (P < 0.0001). Treatment of mildly diabetic mice with nIgM (75 μg 3× per week) restored normoglycemia (n = 5), whereas severely diabetic mice required minimal dose islet transplant with nIgM to restore normoglycemia (n = 4). The mean survival time of BALB/c islet allografts transplanted in streptozotocin-induced diabetic C57BL/6 mice was 41.2 ± 3.3 days for nIgM-treated recipients (n = 4, fifth recipient remains normoglycemic) versus 10.2 ± 2.6 days for controls (n = 5) (P < 0.001). Also, after syngeneic transplantation, time taken to return to normoglycemia was 15.4 ± 3.6 days for nIgM-treated recipients (n = 5) and more than 35 days for controls (n = 4). nIgM therapy demonstrates potential in preventing the onset and progression of autoimmune diabetes and in promoting islet graft survival.