Autoantibodies in neuropsychiatric lupus

The American College of Rheumatology presented a consensus document in 1999 proposing the classification of 19 different syndromes defined by neurological and psychiatric manifestations of systemic lupus erythematosus (SLE). The detection of autoantibodies in patient's serum or cerebrospinal fluid has not been used as diagnostic markers for the proposed neuropsychiatric lupus classifications as their disease associations remain highly contentious. Autoantibodies detected in the serum and/or cerebrospinal fluid, that have been reported to segregate with patients presenting with neuropsychiatric lupus include: (1) anti-neuronal antibodies, (2) brain-lymphocyte cross-reactive antibodies, (3) anti-ribosomal P antibodies, (4) anti-phospholipid antibodies and (5) anti-ganglioside antibodies. Tests for anti-neuronal, anti-brain-lymphocyte cross-reactive and anti-ganglioside antibodies remain highly specialized whereas tests for ribosomal P antibodies and for antiphospholipid antibodies are currently routinely available in most diagnostic laboratories. Anti-ribosomal antibodies segregate with SLE. Antiphospholipid P antibodies are markers for the antiphospholipid syndrome. This syndrome may be associated with another disease, commonly SLE. In this setting, neuropsychiatric manifestations in SLE may arise as a consequence of thrombotic episodes involving the cerebral vasculature. There is a pressing need for antibodies to ribosomal P and to phospholipids to be standardized for routine diagnostic application. We conclude that the search for specific antibody marker(s) that can be applied for the routine laboratory diagnosis for neuropsychiatric lupus remains elusive.     

Mycophenolate mofetil in neuropsychiatric systemic lupus erythematosus

Neuropsychiatric abnormalities frequently occur in patients with systemic lupus erythematosus, affecting as many as 14-75% of people with this disease. High-dose steroid with or without anticoagulation is the mainstay of treatment in neuropsychiatric systemic lupus erythematosus (NPSLE). Use of mycophenolate as a steroid sparing drug may be a potential alternative agent in the therapy of NPLE, but lack of randomized trials and cost prohibit its widespread use. Its safety profile is higher than that of cyclophosphamide and azathioprine. We report a successfully treated case of neuropsychiatric systemic lupus erythematosus, presenting as psychosis, whose long-term remission was maintained on treatment with mycophenolate mofetil.     

Serum lymphocytotoxic antibodies in neuropsychiatric lupus: a serial study

The pathogenesis of neuropsychiatric (NP) SLE remains speculative. A relationship between circulating brain cross-reactive lymphocyte antibodies (LCA) and NP-SLE has been postulated but serial, prospective study of LCA in individual patients with SLE has rarely been performed. In the current study a group of 34 patients with SLE was analyzed using clinical, neurologic, psychiatric, and neuropsychological examinations, together with routine serological tests, to define NP-SLE. Previous history of alloimmunization was also recorded. LCA were measured by a two-stage microcytotoxicity assay against a panel of 25 normal donor B and T cells, at both 40 and 37 degrees C. LCA by this method were found in the serum of 20/34 (58%) SLE, 2/22 (9%) rheumatoid arthritis, and 3/24 (12%) antinuclear-antibody-positive chronic psychiatric patients (P less than 0.01). Analysis of LCA serially in individual SLE patients revealed: (1) No difference in B- or T-cell reactivity at either 4 or 37 degrees C, (2) no significant correlation between previous alloimmunization and the presence of LCA, (3) fluctuations in LCA associated with NP-SLE relapses or remissions, but not with therapy, in 10 patients prospectively studied. A significant positive association was found between the occurrence of single neuropsychiatric events and serial LCA determinations in 180 sera (P less than 0.000001). LCA as measured in this study appear more frequently in SLE than in controls and may indicate active NP-SLE in some patients. Further study of the pathogenic role and diagnostic value of LCA in NP-SLE, including their relationship to subtle neurocognitive changes, is proposed.     

The role of autoantibodies in pediatric neuropsychiatric systemic lupus erythematosus

Neuropsychiatric syndromes are prevalent in pediatric patients with systemic lupus erythematosus (SLE) and often manifest early in disease course and with significant associated morbidity. Postulated pathogenic mechanisms of peripheral and central nervous system events include vasculopathy, autoantibody effects and systemic inflammation. The pathogenic roles of anti-phospholipid, anti-ribosomal-P and anti-neuronal autoantibodies have been examined in both focal and diffuse adult neuropsychiatric syndromes. Few studies have probed associations between these autoantibodies and pediatric neuropsychiatric SLE (NP-SLE). Retrospective review of a large ethnically diverse pediatric SLE cohort revealed anti-phospholipid, anti-ribosomal P, and anti-neuronal antibodies to be more prevalent than in many adult studies. Rates of anti-phospholipid and anti-ribosomal P antibody positivity were similar to those of other pediatric reports. Association between anti-neuronal antibodies and NP-SLE events appeared statistically significant in this cohort. Prospective inception cohort studies will need to be undertaken to investigate the significance and utility of autoantibody testing in pediatric NP-SLE.     

神经精神性狼疮患者免疫学的指标分析

目的：探讨对神经精神性狼疮的发生和早期诊断有意义的免疫学指标。方法：对伴发神经精神性症状和不伴有神经精神性症状的104例红斑狼疮患者C3、C4、IgG、IgA、IgM、抗核抗体（Antinuclear antibody，ANA）、抗核糖体P蛋白（Anti-ribosome P antibody，ARPA）、抗核糖核酸蛋白抗体（Nuclear ribonuclear protein antibody，anti-NRNP）、抗脑神经抗体（Anti-brainantibody，ABA）及抗双链DNA（anti-dsDNA）进行回顾性分析，并在NPLE组将患者按有无合并精神症状进行分组，考查精神症状与上述部分指标的关联。SPSS12.0进行数据处理。结果：ABA阳性例数在NPLE组（62例中51例阳性）分布明显高于非NPLE组（42例中12例阳性），在合并精神症状的NPLE组比无精神症状组比例高（χ^2=4.885，P=0.027），其余各项指标组间比较均无显著性差异。结论：C3、C4水平的降低，IgG、IgA、IgM升高及ANA、APRA、anti-NRNP、anti-dsDNA阳性变化不具有NPLE诊断和预测特异性，是SLE免疫损伤的共有表现；ABA对NPLE的发生及NPLE伴发的精神症状的出现有重要作用。     

Diagnostic performance of aPS/PT antibodies in neuropsychiatric lupus and cardiovascular complications of systemic lupus erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is associated with a constellation of complications affecting multiple organs, including neuropsychiatric manifestations (NPSLE) and ischaemic events, leading to increased long-term morbidity. Antiphospholipid antibodies (aPL) are a major determinant of vascular inflammation and thromboembolic risk. The diagnostic role of anti-phosphatidylserine/prothrombin (aPS/PT) antibodies in this setting is incompletely defined.

Aim: To verify whether aPS/PT add to diagnostics and disease stratification in patients with SLE with or without other aPL.

Methods: 131 consecutive patients were studied, including 20 patients with SLE and secondary antiphospholipid syndrome (APS). aPS/PT IgG and IgM were assessed through ELISA and patients were stratified based on the presence of other aPL, on their clinical and laboratory features at time of blood sampling and on their clinical history. Synthetic indices of disease activity, chronic damage and cardiovascular risk were calculated at time of venipuncture.

Results: Fifty-one (38.9%) patients with SLE had aPS/PT and 15 (11.5%) patients had aPS/PT as the only aPL (aPS/PT-only). aPS/PT-only patients had a significantly higher prevalence of NPSLE than quadruple aPL-negative patients (p?=?.007). Patients with aPS/PT were more likely to have a history of ischaemia, thrombocytopenia and Libman–Sacks’ endocarditis. The presence of aPS/PT also associated with previous accrual of at least one damage item (p?=?.043), but had limited predictive values for damage progression in the short term.

Conclusion: aPS/PT antibodies provide non-redundant information that could contribute to risk assessment and stratification of patients with SLE.     

Posterior reversible encephalopathy syndrome: A neuropsychiatric manifestation of systemic lupus erythematosus

Posterior Reversible Encephalopathy Syndrome (PRES) is an acute neurological syndrome clinically characterized by seizures, altered mental status, headache, and visual disturbances. It is caused by a variety of abnormalities in the endothelial function that ultimately result in vasogenic edema in the circulation of the central nervous system. This is reflected by the neuroimaging findings, that most often show reversible parieto-occipital edema. An important proportion of patients with PRES present with Systemic Lupus Erythematosus (SLE), and its complications, as their sole risk factors. This review describes the relationship between these two clinical entities and explains the pathophysiological models that have been proposed to describe the development of PRES. We explain how SLE can cause alterations in every pathway implicated in the development of PRES. Given the relatively high frequency and the distinct clinical course, PRES in the setting of SLE might be best described as a distinct neuropsychiatric syndrome associated with SLE.     

Epidemiology,characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus

Introduction: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice.

Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events.

Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.