Serum and Cerebrospinal Fluid Autoantibodies in Patients with Neuropsychiatric Lupus Erythematosus. Implications for Diagnosis and Pathogenesis (original) (raw)
Related papers
Arthritis and Rheumatism, 2008
ObjectiveTo examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti–ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti–β2-glycoprotein I, and anti–NR2 glutamate receptor antibodies.To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti–ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti–β2-glycoprotein I, and anti–NR2 glutamate receptor antibodies.MethodsNP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution.NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution.ResultsFour hundred twelve patients were studied (87.4% female; mean ± SD age 34.9 ± 13.5 years, mean ± SD disease duration 5.0 ± 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P = 0.02). Specific clinical–serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events.Four hundred twelve patients were studied (87.4% female; mean ± SD age 34.9 ± 13.5 years, mean ± SD disease duration 5.0 ± 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P = 0.02). Specific clinical–serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events.ConclusionClinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.
Journal of Neuroimmunology, 2010
Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most difficult manifestations of lupus to diagnose. Measurement of serum brain antibodies has contributed to early diagnosis and management of NPSLE before development of a debilitating disease. We aimed to assess the value of serum anti-ganglioside M1 antibodies in prediction of NPSLE, in comparison to other antibodies used in routine laboratory diagnosis of NPSLE. In addition, we are the first to study the relationship between these antibodies and cognitive function in lupus patients. Serum anti-ganglioside M1, anti-ribosomal P protein and anti-cardiolipin antibodies were measured in 30 lupus patients without clinical evidence of NPSLE, aged 8-16 years, and 30 healthy matchedsubjects. Patients were followed-up clinically by monthly neuropsychiatric evaluation and assessment of cognitive function for 12 months. Twelve patients developed neuropsychiatric manifestations during followup. Of those patients, 83.3%, 50% and 16.7% were seropositive for anti-ganglioside M1, anti-ribosomal P and anti-cardiolipin antibodies, respectively at the time of initial evaluation before clinical presentation of NPSLE. There was a significant positive association between anti-ganglioside seropositivity and cognitive dysfunction (P b 0.001). In addition, anti-ganglioside seropositivity had a significant risk for association with cognitive dysfunction (odds ratio: 36; 95% CI: 4.3-302.8). Conclusions: Serum anti-ganglioside M1 antibodies had a higher predictive value for NPSLE than other antibodies used in routine laboratory diagnosis of this disease. Thus, they may be reliable parameters for early diagnosis and management of NPSLE before clinical manifestations ensue. In addition, anti-ganglioside M1 antibodies may play a role in cognitive dysfunction found in some lupus patients.
Arthritis Research & Therapy
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.
Neuropsychiatric lupus and association with cerebrospinal fluid immunoglobulins: a pilot study
The Israel Medical Association journal : IMAJ, 2009
Recent experimental evidence points to brain-reactive antibodies as a key factor in the pathogenesis of neuropsychiatric systemic lupus erythematosus (central nervous system-SLE). However, clinical studies in which circulating (serum) autoantibodies were correlated with neuropsychiatric manifestations have not produced consistent findings. To test the hypothesis that autoantibodies in cerebrospinal fluid are more reflective of functional brain damage. We compared the behavioral profiles of 12 NP-SLE patients, some of whom had immunoglobulin G in their CSF. Western blotting revealed heavy and light chain IgG bands in six patients similar in age to the subgroup of CSF IgG-free patients. A series of serological measures did not differ between the subgroups, but SLEDAI scores and daily steroid doses were higher in patients with IgG in their CSF. All three patients with severe deficits in verbal and executive functions were positive for the CSF IgG, while three other patients with psycho...
Journal of Immunological Methods, 1995
We modifad, and applied lo am, an ELBA established for the detection of brain-rexlive autoantibodies in a murine model of SLE. We found brain-reactive antibody lewls to be significantly higher in lupus patients than in healthy subjects. Tbe antibody levels were significantly higher in lupus patients with central nwvous vstem involvement than in those without. Keywords; H&A; Systemic hapus erythematwsus; Brain-reactive autoantibody 0022-1759/95/$09.50 0 ,995 Ekvicr Science B.V. Ail rights resewed s.sD~oo22-1759(95)oo133-6
Annals of the Rheumatic Diseases, 2011
ObjectiveNeuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events.MethodsPatients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression.ResultsDisease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13...
Clinical Rheumatology, 2005
Neuropsychiatric symptoms are often seen in patients with systemic lupus erythematosus (SLE). To investigate the relationship between involvement of the nervous system and clinical factors, including autoantibodies and the activity of SLE, we retrospectively reviewed 25 patients with neuropsychiatric SLE (NPSLE, mean age: 35.2±12.2 years). As controls 37 SLE patients without neuropsychiatric manifestations (mean age: 31.8±15.8 years) were employed in this study. At the onset no significant differences were seen in any clinical factors between the patients and the controls except for serum antinuclear antibodies. In relapse, the patients with NPSLE showed significantly lower levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores without neuropsychiatric evaluation ( p<0.0001), erythrocyte sedimentation rate (ESR, p<0.005), and antinuclear and anti-double-stranded DNA antibodies ( p<0.005) and higher WBC values ( p<0.05) than at the onset. Also in the patients with relapsing NPSLE similar significant differences were seen in these parameters between onset and relapse ( p<0.005). Despite a lack of significant differences, the cerebrospinal fluid showed lower values in cell counts, total protein, and IgG in relapse than at onset. These results suggest that there are no clinical factors that predict the development of NPSLE and that relapse can occur with low disease activity in the nervous system even with an inactive state of other organ involvement. Since NPSLE may suddenly relapse with a slight change in common disease activation markers, including inflammatory reactions, autoantibodies, and complements in serum and CSF findings, adequate corticosteroid and/or immunosuppressive agents should be given at the onset and gradually be tapered after recovery, while looking out for recurrence.