Proteomic Analysis of Cerebrospinal Fluid: A Search for Biomarkers of Neuropsychiatric Systemic Lupus Erythematosus

2019 ◽  
Vol 16 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Johanna Pedroza-Díaz ◽  
Tania Paola Luján Chavarria ◽  
Carlos Horacio Muñoz Vahos ◽  
Diego Francisco Hernández Ramírez ◽  
Elizabeth Olivares-Martínez ◽  
...  

Background: Neuropsychiatric systemic lupus erythematosus or NPSLE, as its name suggests, refers to the neurological and psychiatric manifestations of Systemic Lupus Erythematosus (SLE). In clinical practice, it is often difficult to reach an accurate diagnosis, as this disease presents differently in different patients, and the available diagnostic tests are often not specific enough. Objectives: The aim of this study was to search for proteomic biomarkers in cerebrospinal fluid that could be proposed as diagnostic aids for this disease. Methods: The proteomic profile of cerebrospinal fluid samples of 19 patients with NPSLE, 12 patients with SLE and no neuropsychiatric manifestation (SLEnoNP), 6 patients with neuropsychiatric symptoms but no SLE (NPnoSLE), 5 with Other Autoimmune Disorders without neuropsychiatric manifestations (OADs), and 4 Healthy Controls (HC), were obtained by two-dimensional gel electrophoresis and compared using ImageMaster Platinum 7.0 software. Results: The comparative analysis of the different study groups revealed three proteins of interest that were consistently over-expressed in NPSLE patients. These were identified by mass spectrometry as albumin (spot 16), haptoglobin (spot 160), and beta-2 microglobulin (spot 161). Conclusion: This work is one of the few proteomic studies of NPSLE that uses cerebrospinal fluid as the biological sample. Albumin has previously been proposed as a potential biomarker of rheumatoid arthritis and SLE, which is coherent with these results; but this is the first report of haptoglobin and beta-2 microglobulin in NPSLE, although haptoglobin has been associated with increased antibody production and beta-2 microglobulin with lupus nephritis.

Author(s):  
Elias Manca

AbstractSystemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus. Neuropsychiatric symptoms can range from relatively mild manifestations, such as headache, to more severe complications, such as psychosis. The evaluation of the presence of the autoantibodies in the serum of these patients is the most helpful diagnostic tool for the assessment of the disease. The scientific progresses achieved in the last decades helped researchers and physicians to discover some of autoepitopes targeted by the autoantibodies, although the majority of them have not been identified yet. Additionally, the central nervous system is full of epitopes that cannot be found elsewhere in the human body, for this reason, autoantibodies that selectively target these epitopes might be used for the differential diagnosis between patients with and without the neuropsychiatric symptoms. In this review, the most relevant data is reported with regard to mechanisms implicated in the production of autoantibodies and the most important autoantibodies found among patients with systemic lupus erythematosus with and without the neuropsychiatric manifestations.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 604.1-604
Author(s):  
R. Monahan ◽  
A. Blonk ◽  
H. Middelkoop ◽  
M. Kloppenburg ◽  
T. Huizinga ◽  
...  

Background:The presence of a ‘fog’ is frequently reported by patients with systemic lupus erythematosus (SLE). However, little is known about this lupus fog: it is thought to be a result of cognitive dysfunction, but fogs can also be the result of dissociation. The Dissociative Experience Scale-II (DES) is a standardized tool to study dissociation. In the general adult population, scores range from 4.4-14.1-3Objectives:We aimed to study the prevalence of dissociative symptoms including dissociative fog in patients with SLE and neuropsychiatric symptoms.Methods:Patients visiting the tertiary referral center for neuropsychiatric systemic lupus erythematosus (NPSLE) of the LUMC between 2007-2019 were included. All patients underwent a standardized multidisciplinary assessment. Patients were classified as NPSLE if neuropsychiatric symptoms were attributed to SLE and immunosuppressive or anticoagulant therapy was initiated, otherwise patients were classified as minor/non-NPSLE. Dissociation was studied using the DES. The DES separates different types of dissociative symptoms: amnesia, absorption/imagination and derealization/depersonalization. It also contains one question regarding evaluating the presence of a dissociative fog: “Some people sometimes feel as if they are looking at the world through a fog, so that people and objects appear far away or unclear”. All statements (n = 28) regarding dissociative symptoms are rated from ‘none of the time’ to ‘all of the time’ (0-100%); scores >25 are considered abnormal. A multiple regression analysis (MRA) were performed to compare dissociation in patients with and without NPSLE. DES results are presented as median (range) and MRA as odds ratio (OR) and 95% confidence interval (CI).Results:DES questionnaires were available for 337 patients, of which 97 had the diagnosis NPSLE (29%). Mean age in patients with NPSLE was 41 ± 13 years and 84% was female. In minor/non-NPSLE, median age was 44 ± 14 years and 87% was female.Median dissociation was 7 (0-75) and did not differ between patients with minor/non-NPSLE and NPSLE (OR: 1.0 (95% CI: -0.9; 1.1)). The most common type of dissociation was absorption/imagination (median: 12, range 0-75) and depersonalization/derealization was infrequent (median: 1, range 0-84). 43 patients (13%) had an abnormal score (>25) on the dissociative fog question.Conclusion:Dissociative symptoms are within normal range in patients with SLE and neuropsychiatric symptoms, regardless of underlying etiology. Dissociative fog seems uncommon and therefore lupus fog is most likely not the result of dissociation.References:[1]Bernstein EM and Putnam FW. Development, reliability, and validity of a dissociation scale. J Nerv Ment Dis 1986; 174: 727-735. 1986/12/01. DOI: 10.1097/00005053-198612000-00004.[2]Maaranen P, Tanskanen A, Honkalampi K, et al. Factors associated with pathological dissociation in the general population. Aust N Z J Psychiatry 2005; 39: 387-394. 2005/04/30. DOI: 10.1080/j.1440-1614.2005.01586.x.[3]van IJzendoorn MH and Schuengel C. The measurement of dissociation in normal and clinical populations: Meta-analytic validation of the Dissociative Experiences Scale (DES). Clinical Psychology Review 1996; 16: 365-382. DOI: 10.1016/0272-7358(96)00006-2.Table 1.Presence of dissociation in patients with SLE and neuropsychiatric symptomsTotal cohort(n = 337)Minor/non-NPSLE(n = 240)NPSLE(n = 97)DES (median, range)Total questionnaire7 (0 - 75)8 (0 - 66)6 (0 – 75)Amnesia5 (0 - 76)5 (0 - 68)4 (0 - 76)Absorption/imagination12 (0 – 75)13 (0 – 75)10 (0 – 73)Depersonalization/derealization1 (0 – 84)1 (0 – 73)1 (0 – 84)Dissociative fog* 0 (0-100)0 (0-100)0 (0-100)DES = Dissociative Experience Scale NPSLE = neuropsychiatric systemic lupus erythematosus.*Dissociative fog is question 28 of the DES-IIDisclosure of Interests:None declared


2016 ◽  
Vol 165 ◽  
pp. 29-34 ◽  
Author(s):  
Takeshi Ushigusa ◽  
Kunihiro Ichinose ◽  
Shuntaro Sato ◽  
Toru Michitsuji ◽  
Toshimasa Shimizu ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Kentaro Isoda ◽  
Tohru Takeuchi ◽  
Shigeki Makino ◽  
Toshiaki Hanafusa

We report a patient with systemic lupus erythematosus complicated by toluene poisoning. She had erythema, alopecia, arthralgia, and various neurological symptoms. Laboratory findings showed leukocytopenia, low levels of complements, and anti-dsDNA antibody. However, normal interleukin-6 level and IgG index of cerebrospinal fluid and brain magnetic resonance imaging and single photon emission computed tomography findings suggested that her neurological symptoms were caused by metabolic disorder but not neuropsychiatric systemic lupus erythematosus. Erythema, alopecia, and arthralgia improved rapidly after administration of prednisolone and tacrolimus, whereas neurological symptoms improved only gradually. Because of a history of exposure to toluene, her neurological symptoms were considered to be due to toluene poisoning. The differentiation of toluene poisoning from neuropsychiatric systemic lupus erythematosus based on symptoms is difficult because both induce various neuropsychiatric disorders. Laboratory findings of cerebrospinal fluid, radiological findings, and medical interview were useful for differentiation of toluene poisoning from neuropsychiatric systemic lupus erythematosus.


Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1210-1211
Author(s):  
Tomoyuki Asano ◽  
Shuzo Sato ◽  
Hiroko Kobayashi ◽  
Yoshinobu Kariya ◽  
Hiromi Ito ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document