双相障碍中酪蛋白膳食抗原的免疫激活。

Immune activation by casein dietary antigens in bipolar disorder.

机构信息

Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA.

出版信息

Bipolar Disord. 2010 Dec;12(8):834-42. doi: 10.1111/j.1399-5618.2010.00879.x.

DOI:10.1111/j.1399-5618.2010.00879.x

PMID:21176030

Abstract

OBJECTIVES

Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals.

METHODS

Anti-bovine casein immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75 individuals with bipolar disorder and 65 controls. Epitope recognition was evaluated in immunoassays by cross neutralization with anti-bovine casein polyclonal antibodies of defined reactivity. Group-specific reactivity and associations with symptom severity scores were detected with age-, gender-, and race-controlled regression models.

RESULTS

Individuals with bipolar disorder had significantly elevated anti-casein IgG (t-test, p ≤0.001) compared to controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar disorder [n=75, 95% confidence interval (CI): 1.31-12.08, p ≤0.015], 5.26 for the bipolar I subtype (n=56, 95% CI: 1.66-16.64, p ≤0.005), and 3.98 for bipolar disorder with psychosis (n=54, 95% CI: 1.32-12.00, p ≤0.014). Lithium and/or antipsychotic medication did not significantly affect anti-casein IgG levels. Casein IgG measures correlated with severity of manic (R(2) =0.15, 95% CI: 0.05-0.24, p ≤0.02) but not depressive symptoms. Unlike controls, sera from individuals with bipolar disorder did not inhibit binding of casein-reactive animal sera (t-test/χ(2) , p ≤0.0001).

CONCLUSIONS

Anti-casein IgG associations with bipolar I diagnoses, psychotic symptom history, and mania severity scores suggest that casein-related immune activation may relate to the psychosis and mania components of this mood disorder. Case-control differences in epitope recognition implicate disease-related alterations in how the casein molecule is digested and/or how resulting casein-derived structures are rendered immunogenic.

摘要

目的

炎症和其他免疫过程与精神疾病的关系越来越密切。针对双相情感障碍的特定抗原触发因素尚不清楚。我们测试了针对牛乳清蛋白的抗体是否与双相情感障碍有关，以及患者是否识别出不同于对照个体的乳清蛋白表位。

方法

采用固相免疫分析法检测 75 例双相情感障碍患者和 65 例对照者的抗牛乳清蛋白 IgG 水平。通过用抗牛乳清蛋白多克隆抗体进行交叉中和，评估免疫分析中的表位识别，该多克隆抗体具有明确的反应性。采用年龄、性别和种族对照回归模型检测组特异性反应性与症状严重程度评分的相关性。

结果

与对照组相比，双相情感障碍患者的抗乳清蛋白 IgG 显著升高（t 检验，p≤0.001）。乳清蛋白 IgG 血清阳性使双相情感障碍的比值比为 3.97（n=75，95%置信区间[CI]：1.31-12.08，p≤0.015），双相 I 型亚组的比值比为 5.26（n=56，95%CI：1.66-16.64，p≤0.005），精神病性双相情感障碍的比值比为 3.98（n=54，95%CI：1.32-12.00，p≤0.014）。锂盐和/或抗精神病药物并不显著影响抗乳清蛋白 IgG 水平。乳清蛋白 IgG 水平与躁狂严重程度呈正相关（R(2)=0.15，95%CI：0.05-0.24，p≤0.02），但与抑郁症状无关。与对照组不同，双相情感障碍患者的血清不能抑制乳清蛋白反应性动物血清的结合（t 检验/χ(2) ，p≤0.0001）。