免疫失调是精神分裂症(SZ)和双相情感障碍(BD)病理生理学的一个重要方面,不仅包括炎症,还包括反映异常体液免疫反应的自身免疫过程。鉴于B细胞活化因子(BAFF)是B淋巴细胞调节的一个组成部分,本研究调查了SZ和BD中的BAFF。255名SZ患者,通过(i)比较SZ的sBAFF循环水平,对407名BD患者和185名健康对照(HC)进行了可溶性BAFF(sBAFF)三个方面的调查,BD和HC,(ii)确定sBAFF的循环水平与功能相关多态性的基因型分布之间的潜在相关性,即TNFSF13B3UTR插入-缺失多态性(GCTGT>A),(iii)分析sBAFF水平和3个UTR插入缺失基因型与疾病风险之间的关系,患者的临床特征和循环中有效的炎症分子水平。此外,在患者亚组中,我们还搜索了sBAFF水平与过去感染事件的污名以及循环全身自身抗体或针对中枢神经系统(CNS)结构的抗体阳性之间的可能相关性.研究血液来源的血清和DNA,我们观察到SZ和BD患者的循环sBAFF水平明显更高,与HC(p=5.3*10-10和p=4.4*10-09)。患者经历急性发作,与稳定患者相比,在急性发作之间,表现出更高的sBAFF水平(p=0.017)。在SZ患者中,sBAFF水平升高与:(i)阳性精神病症状升高(PANSSpos),(ii)童年创伤(身体虐待)的历史,和(iii)全球功能(GAF)得分低(p=0.024,p=0.024和p=0.041)。我们还发现,在SZ和BD患者中,BAFFIns/Del基因型的分布与循环sBAFF水平显着相关(p=0.0004)。在SZ和BD组群中,升高的sBAFF水平也与升高的促炎标志物水平相关(p<0.001)。关于传染性污名,只有血清阳性的患者,相对于血清阴性,对于单纯疱疹病毒(HSV)1免疫球蛋白(Ig)G抗体显示出与高sBAFF水平显着相关(p=0.013)。相比之下,全身性或CNS自身抗体阳性与sBAFF水平降低显著相关,与无自身抗体的患者相比(p=0.0017)。总的来说,我们的研究结果表明,BAFF可能是一个有前途的跨眼图炎症生物标志物,可能提供预测,诊断,以及SZ和BD管理的预后工具。因此,考虑到包括针对BAFF的靶向单克隆抗体的免疫治疗治疗选择的可用性,结果具有切实可行的临床效用。
Immune dysregulation is an important aspect of schizophrenia (SZ) and bipolar disorders (BD) pathophysiology, including not only inflammatory but also autoimmune process reflective of abnormal humoral immune responses. Given that B cell-activating factor (BAFF) is an integral aspect of B lymphocyte regulation, the current study investigated BAFF in SZ and BD. 255 SZ patients, 407 BD patients and 185 healthy controls (HC) were investigated across three aspects of soluble BAFF (sBAFF) by (i) comparing sBAFF circulatory levels across SZ, BD and HC, (ii) determining potential correlations between the circulating levels of sBAFF and the genotype distribution of a functionally relevant polymorphism, namely the TNFSF13B 3\'UTR insertion-deletion polymorphism (GCTGT>A), (iii) analyzing relationships between both sBAFF levels and 3\'UTR insertion-deletion genotypes and disease risk, patients clinical characteristics and circulating levels of potent inflammatory molecules. In addition, in subsets of patients, we also searched for possible correlations between sBAFF levels and stigma of past infectious events as well as positivity for circulating systemic autoantibodies or those directed against central nervous system (CNS) structures. Studying blood derived serum and DNA, weobserved that circulating sBAFF levels were significantly higher in SZ and BD patients, versus HC (p = 5.3*10-10and p = 4.4*10-09). Patients experiencing acute episodes, versus stable patients, in between acute episodes, exhibited higher sBAFF levels (p = 0.017).In SZ patients, positive correlations were observed between elevated sBAFF levels and: (i) elevated positive psychotic symptoms (PANSS pos), (ii) history of childhood trauma (physical abuse), and (iii) low scores on global functioning (GAF) (p = 0.024, p = 0.024, and p = 0.041).We also found that the distribution of the BAFF Ins/Del genotypes was significantly correlated with circulating sBAFF levels in SZ and BD patients (p = 0.0004). Elevated sBAFF levels were also correlated with increased levels of pro-inflammatory markers in both SZ and BD cohorts (p < 0.001). Regarding infectious stigma, only patients seropositive, versus seronegative, for herpes simplex virus (HSV)1 immunoglobulin (Ig)G antibodies exhibited a significant association with high sBAFF levels (p = 0.013). In contrast, positivity for systemic or CNS autoantibodies was significantly associated with reduced sBAFF levels, compared to patients without autoantibodies (p = 0.0017). Overall, our findings indicate that BAFF may be a promising trans-nosographic biomarker of inflammation that is likely to offer predictive, diagnostic, and prognostic tools for the management of SZ and BD. The results therefore have practicable clinical utility given the availability of immunotherapeutic treatment options including targeted monoclonal antibodies against BAFF.