Spezialetti R, Bluestein H G, Peter J B, Alexander E L
Specialty Laboratories, Inc., Santa Monica, California.
Am J Med. 1993 Aug;95(2):153-60. doi: 10.1016/0002-9343(93)90255-n.
Patients with Sjögren's syndrome (SS) may develop nonfocal (i.e., psychiatric and/or cognitive dysfunction) as well as focal, neuropsychiatric disease (CNS-SS). Anti-ribosomal P and anti-neuronal antibodies have been associated with nonfocal neuropsychiatric disease in systemic lupus erythematosus (SLE), particularly psychosis and depression. This study examines the spectrum of psychiatric and cognitive dysfunction observed in SS patients with focal, as well as nonfocal, central nervous system (CNS) disease and relates these observations to the presence of serum and cerebrospinal fluid (CSF) anti-ribosomal and anti-neuronal antibodies.
One hundred thirty-one patients--patients with primary SS (n = 91), patients with secondary SS (n = 34), and mothers of infants with neonatal lupus erythematosus (NLE) (n = 6)--were studied. Patients were referred to a large tertiary referral center and the population was highly selected for CNS disease. Patients were evaluated clinically for focal and nonfocal CNS disease. Sera from 131 patients and 34 paired sera/CSF samples were examined by enzyme-linked immunosorbent assay and radioimmunoassay for the presence of anti-ribosomal P and anti-neuronal autoantibodies, respectively. Clinical features were categorized and autoantibody profiles obtained and correlated independently for statistical significance. Data were analyzed using the two-tailed Fisher exact test.
Psychiatric or cognitive impairment, usually mild or moderate, occurred in over 80% (63 of 77) of this highly selected population of SS patients, and more than 60% of patients (48 of 77) had both. Anti-ribosomal P antibodies occurred in six (4.6%) patients with SS and related disorders. None of the patients with primary SS had anti-ribosomal P antibodies, whereas they were present in a small number of patients with secondary SS (i.e., 4 of 34 [12%]) and in 2 of 6 mothers of infants with NLE. There was no correlation between nonfocal CNS disease, including psychosis or severe depression, and the presence of anti-ribosomal P antibodies. Paired serum CSF samples from 34 SS patients with active CNS disease, including 6 with psychosis and 5 with severe depression, did not contain either anti-ribosomal P or anti-neuronal antibodies. Anti-ribosomal P and anti-neuronal antibodies were present in a control subset of SLE patients defined serologically by the presence of anti-nDNA antibodies.
Patients with primary SS associated with CNS disease, including psychosis and depression, do not have serum or CSF autoantibodies to ribosomal P peptide or neuronal antigens, detected by binding to neuroblastoma cells. Thus, autoantibodies associated with nonfocal or diffuse CNS disease in classical SLE (particularly psychosis and depression) are not present in CNS-SS. The observations suggest that nonfocal CNS disease in CNS-SS and CNS-SLE may be mediated by different immunopathologic mechanisms. Potentially, these observations may have diagnostic and therapeutic implications in the management of patients with CNS-SS and patients with CNS-SLE.
干燥综合征（SS）患者可能会出现非局灶性（即精神和/或认知功能障碍）以及局灶性神经精神疾病（中枢神经系统干燥综合征，CNS-SS）。抗核糖体P抗体和抗神经元抗体与系统性红斑狼疮（SLE）中的非局灶性神经精神疾病有关，尤其是精神病和抑郁症。本研究调查了患有局灶性和非局灶性中枢神经系统（CNS）疾病的SS患者中观察到的精神和认知功能障碍谱，并将这些观察结果与血清和脑脊液（CSF）中抗核糖体和抗神经元抗体的存在情况相关联。
研究了131名患者，包括原发性SS患者（n = 91）、继发性SS患者（n = 34）以及新生儿狼疮（NLE）婴儿的母亲（n = 6）。患者被转诊至一家大型三级转诊中心，该人群因CNS疾病而被高度筛选。对患者进行了局灶性和非局灶性CNS疾病的临床评估。分别通过酶联免疫吸附测定和放射免疫测定检测了131名患者的血清以及34对血清/CSF样本中抗核糖体P和抗神经元自身抗体的存在情况。对临床特征进行分类，获取自身抗体谱并独立进行相关性分析以确定统计学意义。使用双侧Fisher精确检验分析数据。
在这个经过高度筛选的SS患者群体中，超过80%（77例中的63例）出现了精神或认知障碍，通常为轻度或中度，超过60%的患者（77例中的48例）两者都有。6例（4.6%）SS及相关疾病患者出现了抗核糖体P抗体。原发性SS患者中无一例有抗核糖体P抗体，而少数继发性SS患者（即34例中的4例[12%]）以及6例NLE婴儿的母亲中有2例出现了该抗体。包括精神病或重度抑郁症在内的非局灶性CNS疾病与抗核糖体P抗体的存在之间没有相关性。来自34例患有活动性CNS疾病的SS患者的配对血清CSF样本，包括6例患有精神病和5例患有重度抑郁症的患者，均未检测到抗核糖体P或抗神经元抗体。在通过抗nDNA抗体的存在血清学定义的SLE患者对照子集中存在抗核糖体P和抗神经元抗体。
与CNS疾病（包括精神病和抑郁症）相关的原发性SS患者，通过与神经母细胞瘤细胞结合检测，其血清或CSF中不存在针对核糖体P肽或神经元抗原的自身抗体。因此，经典SLE中与非局灶性或弥漫性CNS疾病（尤其是精神病和抑郁症）相关的自身抗体在CNS-SS中不存在。这些观察结果表明，CNS-SS和CNS-SLE中的非局灶性CNS疾病可能由不同的免疫病理机制介导。这些观察结果可能对CNS-SS患者和CNS-SLE患者的管理具有诊断和治疗意义。
