Anti–U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease

Abstract

Objective. To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE).Methods. The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. Systemic lupus erythematosus (SLE) is a chronic, remitting and relapsing, multisystem autoimmune disease that predominantly affects women. Neuropsychiatric SLE (NPSLE) involving the central nervous system (CNS; central NPSLE) is a severe, life-threatening manifestation. The overall prevalence of NPSLE varied from 14% to 75% in a representative selection of studies using the American College of Rheumatology (ACR) nomenclature (1). In fact, NPSLE may affect mortality in SLE and is associated with a significant negative impact on a patient's quality of life. However, 41% of all CNS manifestations in patients with SLE may be attributed to factors other than lupus (2).Although the pathophysiology of most NPSLE cases is not well determined, a particular subset of

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

“…immunoglobulins (Igs) and cytokines into the CSF, is now considered as an important component in NPSLE development [37][38][39]. Increased CSF levels of Igs, Abs and proinflammatory cytokines, as well as elevated albumin concentration, are indicative of increased BBB's permeability [40][41][42], and have additionally been associated with NP manifestations [40,[43][44][45][46][47].…”

Pathogenesis of Neuropsychiatric Syndromes of Systemic Lupus Erythematosus

“…Sato et al demonstrated that CSF anti-RNP were associated with NPSLE and CNS manifestations in mixed connective tissue disease as a more specific marker of NPSLE than anti-P or anti-NR2 [24]. However, the elevation of CSF anti-RNP was not specific in ACS or diffuse NPSLE, since CSF anti-RNP was also elevated in patients with focal NPSLE, including aseptic meningitis, headache, demyelinating disorder or movement disorder [24].…”

Auto-antigenic Properties of the Spliceosome as a Molecular Tool for Diagnosing Systemic Lupus Erythematosus and Mixed Connective Tissue Disease Patients

“…By contrast, patients diagnosed with SLE and other autoimmune syndromes were included during the production of each of the four classification criteria sets for MCTD (Amigues et al, 1996). Nevertheless, these studies did not included well characterized MCTD cases and rather choose the presence of positive anti-U1 snRNP antibodies as patient inclusion criteria despite knowing these antigens elicit a response in SLE and MCTD subjects (Amigues et al, 1996;Sato et al, 2010;Nagai et al, 2012.…”

“…Autoimmune responses to U1 snRNP specific proteins, including U1Ap, have been described in patients diagnosed with Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD) (de Wildt et al, 1997;Faig and Lutz , 2003;McClain et al, 2004;Sato et al, 2010). In some patient cohorts, anti-U1Ap responses have been reported to be the first anti-U1-snRNP to develop (McClain et al, 2004).…”

“…Clinically, kidney damage is more frequent in SLE while lung malfunction is often observed in MCTD patients (De Clerck et al, 1989;Sawai et al 1994;Yoshida et al, 1994;Watanabe et al, 2012). Previous studies have described elevated IgG autoimmune response to U1Ap fragments in both SLE and MCTD patients (Sato et al, 2010). In addition, Vlachoyiannopoulos et al (1996) reported that SLE but not MCTD patients showed a predominant immunoglobulin M (IgM) response to snRNP subunits, including U1Ap.…”