Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus.

Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients ( n = 107) and age- and sex-matched population-based controls ( n = 107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis.

Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.

Perceived future in chronic pain: the relationship between outlook on future and empirically derived psychological patient profiles.

Perceived (subjective) future has been found to be a significant factor in explaining the relationship between pain and pain-related distress. The present study is based on the assumption that chronic pain patients with the three psychological profiles introduced by Turk and Rudy in 1988 could also be found in a sample of chronic pain patients and if so, these profiles have different perspectives on the future. The Multidimensional Pain Inventory (MPI) and The Future Scale were used to collect data from 569 patients with heterogeneous non-malignant chronic pain. A cluster analysis was conducted, where the resulting clusters closely resembled the profiles labelled by Turk and Rudy as 'dysfunctional', 'interpersonally distressed' and 'adaptive coper'. The results indicated that patients with adaptive coper profile have a more positive perception, while those with an interpersonally distressed profile have a more negative perception of the future. With an increased duration of pain, the proportion of the adaptive coper category decreased linearly, while an opposite trend was noted for the interpersonally distressed category. These results may better enable profiled psychological interventions in clinical pain treatment, e.g. by providing patients with therapies focused on positive future orientation, resulting in increased motivation for health-seeking behaviour and better abilities to cope with pain.

Subjective future as a mediating factor in the relation between pain, pain-related distress and depression.

The coincidence of chronic pain, psychological distress and depression has been well documented in several studies. However, there is still debate about the type of causality linking these factors and whether psychological distress and depression precede or are a consequence of pain. This study contributes to this debate through an analysis of the latent structure behind these complex concepts. To test the hypothesis that subjective future (i.e. how the pain patient perceives the future) has an impact on pain, data were analysed from 660 chronic pain patients who were tested with The Multidimensional Pain Inventory (MPI), The Symptom Distress Checklist (SCL-90) and a Future Scale, which was constructed from items of the Sense of coherence-scale. By use of path analysis and structural equation modeling (S.E.M.) four latent constructs were tested: Pain, Interference, Distress and Subjective future. The results indicated that Subjective future has a strong impact on Distress, is a mediating variable, which contributes to conceptually explaining and practically nullifying the relationship between Pain and Distress, and finally that Pain is a concept, that changes with increasing duration. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Busy with pain: disorganization in subjective time in experimental pain.

The cold pressor test was used to investigate perception of time and change of mood in subjects experiencing pain. Using a within-group design, 15 subjects were tested in a pain vs no-pain condition. Subjects were requested to fill in the mood adjective checklist (MACL) concerning the mood factors of activity, calmness and pleasantness, and were interviewed about their perceptions before and immediately after each condition. The results indicated that subjects in the pain condition estimated retrospective time passage as significantly shorter, indicating a disorganization of temporal orientation (the relative dominance of past, present and future in a person's thought). In addition, results indicated that many of the subjects in the pain condition, although underestimating time, experienced time as long-lasting. The main finding concerning mood was that the activity level was increased, and calmness and pleasantness were significantly reduced in the pain condition. The main conclusion is that pain per se changes the perception of duration of time intervals and temporal orientation within the same individual.

The long-lasting now: disorganization in subjective time in long-standing pain.

This paper presents a phenomenological-hermeneutical case study on long-standing pain (LP), a public health problem of great importance. Although there has been intensive research interest in this phenomenon, most studies have been based on traditional medical and cognitive-behavioral approaches. Our thesis is that new frames of reference can provide additional heuristic insights. The phenomenon of LP shows a strong association with existential factors. Our case study focuses on the meaning-structure of lived temporality, a fundamental existential constituent in the lifeworld of the pain patient. A series of in-depth interviews with four subjects showed that lived temporality is disrupted in pain experience, causing a disorganization of the patient's being in the world. The results generate several hypotheses about implications for time estimation in pain experience.

A comparison of propofol and methohexital as anesthetic agents for ECT: effects on seizure duration, therapeutic outcome, and memory.

The effects of the anesthetic agents propofol and methohexital on seizure duration, clinical outcome, recovery, and memory in electroconvulsive therapy (ECT) were studied in a double-blind trial. The study comprised 53 patients, 47 patients with major depression and six patients with other diagnoses according to DSM-III. Several recent clinical studies with a crossover design have shown a reduced seizure duration for anesthesia with propofol in comparison with both methohexital and thiopental. Propofol significantly reduced the seizure duration in this study without reducing the therapeutic outcome as measured by the Montgomery-Asberg Depression Rating Scale. Propofol did not significantly alter the length of the course of ECT; however, a slightly prolonged course for women cannot be completely ruled out. There were no significant differences between the two agents in effects on recovery times after anesthesia and on anterograde memory. In general, it seems that propofol is as effective as methohexital as an induction agent for ECT.

Adaptation of human atrial muscle repolarisation after high rate stimulation.

We analysed the effect of a sudden change from a high rate of stimulation to a "physiological" rate upon the repolarisation of human atrial muscle. Microelectrode technique was used to study the effect upon the action potential (AP) recorded from myocardial specimens obtained during open heart surgery in nine patients. Suction electrodes were used to record monophasic action potentials (MAPs) in 12 patients undergoing electroconversion of atrial fibrillation. The abrupt change from 30 min of high-rate stimulation of the atrial specimen to a pacing rate of 60 per min resulted in a successive prolongation of the atrial myocardial AP duration so that 50% of the prolongation was reached after 3 min according to an exponential analysis. A similar prolongation of repolarisation was seen in the MAP recordings after conversion of atrial fibrillation to sinus rhythm and during regular atrial stimulation at a rate of 100 per min. In these recordings, the time needed to reach 50% of the prolongation of the MAP after DC conversion was about 7 min. The findings demonstrate that human atrial muscle undergoes an adaptation of repolarisation after abrupt slowing from a fast stimulation rate. A steady-state level of the AP or MAP duration is reached 10 to 15 min after the change of rate. Together with earlier studies, these experiments indicate, that when right atrial MAP recording is done for assessment of the likelihood of the patient's remaining in sinus rhythm after conversion of atrial fibrillation, the recording must be made within a few minutes of the conversion.