The Common γc-Cytokines and Transplantation Tolerance

Transplant rejection, like tolerance, is a T cell-dependent event.There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage with the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor γc chain (also called the common γc) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that γc cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that γc cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of γc cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.     

The Unique Features of Vasculitis in Behçet’s Syndrome

The presence of a true vasculitis is difficult to discern in some of the more common manifestations of Behçet’s syndrome, like the papulopustular lesions of the skin. On the other hand, a true vasculitis is seen in all vessel sizes in the majority of the patients. The pathogenesis is not yet known. A Th1-type inflammatory reaction is seen like in some other primary vasculitides. However, in contrast to other vasculitides, granuloma formation is absent. Behçet’s syndrome is unique among the vasculitides with its differing geographic distribution in disease expression, the distinctly more severe disease among the male, the predominance of venous disease, and the generally abating disease course with lack of associated increased atherosclerosis.     

Classifying Fibromyalgia Syndrome as a Mental Disorder?—An Ambulatory Assessment Study

Purpose

Fibromyalgia syndrome (FMS) is associated with psychological distress. The recent revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) raises the question of whether FMS is classifiable as “somatic symptom disorder” (SSD) and consequently as a mental disorder. To address this, the present ambulatory assessment study focuses on the everyday life occurrence of SSD symptoms in FMS and their predictive value concerning severity indicators of widespread pain.

Method

Ambulatory data were assessed six times daily on 14 consecutive days via iPod. Twenty-eight women suffering from FMS indicated symptoms associated with SSD (somatic illness beliefs, health anxiety, time/energy devoted to pain, or health concerns) and momentary pain levels. Questionnaires regarding potential covariates (such as somatization, depression, health status) were completed at two additional sessions in the research laboratory.

Results

On average, SSD symptoms occurred three to four times daily and were mild to moderate in severity. Furthermore, these symptoms were both concurrently and prospectively associated with momentary pain intensity and subjective impairment by pain. Twenty percent of the variance in pain intensity and 28 % of the variance in subjective impairment were explained by momentary variables (SSD symptoms and intake of pain medication). Eighty-two percent of persons with FMS fulfilled the psychological SSD criterion when considering everyday occurring symptoms with at least mild severity.

Conclusion

FMS might be diagnosed as a mental disorder according to DSM-5 in many cases. SSD symptoms proved to have predictive value for FMS severity and may thus have clinical relevance for diagnostic, prognostic, and intervention purposes.

     

Cogan's Syndrome—Clinical Guidelines and Novel Therapeutic Approaches

Cogan's syndrome (CS) is a rare chronic inflammatory disorder, classically characterized by interstitial keratitis and sensorineural hearing loss. Recurrent episodes of inner ear disease might result in deafness. In some patients, it may also be accompanied by systemic vasculitis. Diagnosis of CS is often missed or delayed due to its rarity, the nonspecific clinical signs at onset, and the lack of a confirmatory diagnostic test. The mechanisms responsible for CS are unknown; however, in the last decade, the pathogenesis has been somewhat elucidated, suggesting that the disease is a result of inner ear autoimmunity. The autoimmune hypothesis postulates the triggering of the disease by a viral infection via a number of mechanisms, which are mainly as follows: antigenic mimicry, self-perpetuating inflammation by cytokine release, and unveiling hidden epitopes. Aside from its clinical resemblance to other autoimmune disorders, some autoantigen has apparently been identified, namely, CD148 and connexine 26. Treatment should begin as early as possible. While treatment is based primarily on glucocorticoids, there is no standard alternative for patients who respond poorly. Failure of conventional treatment could lead to profound sensorineural hearing loss. From the limited data we have, infliximab seems to be the most promising biological remedy, enabling steroid tapering and leading to improvement in auditory/ocular disease, with better results when administered in early stages. Proposed guidelines for the use of infliximab in CS are found in the last table of the review, in an attempt to define the proper timing for initiating infliximab treatment in order to avoid permanent disability.     

Sjögren’s Syndrome—Study of Autoantigens and Autoantibodies

The presence of autoantibodies is the hallmark of systemic autoimmune diseases. During the past 30 years, intense clinical and basic research have dissected the clinical value of autoantibodies in many autoimmune diseases and offered new insights into a better understanding of the molecular and functional properties of the targeted autoantigens. Unraveling the immunologic mechanisms underlying the autoimmune tissue injury, provided useful conclusions on the generation of autoantibodies and the perpetuation of the autoimmune response. Primary Sjögren’s syndrome (pSS) is characterized by the presence of autoantibodies binding on a vast array of organ and non-organ specific autoantigens. The most common autoantibodies are those targeting the Ro/La RNP complex, and they serve as disease markers, as they are included in the European–American Diagnostic Criteria for pSS. Other autoantibodies are associated with particular disease manifestations, such as anti-centromere antibodies with Raynaud’s phenomenon, anti-carbonic anhydrase II with distal renal tubular acidosis, anti-mitochondrial antibodies with liver pathology, and cryoglobulins with the evolution to non-Hodgkin’s lymphoma. Finally, autoantibodies against autoantigens such as alpha- and beta-fodrin, islet cell autoantigen, poly(ADP)ribose polymerase (PARP), NuMA, Golgins, and NOR-90 are found in a subpopulation of SS patients without disease specificity, and their utility remains to be elucidated. In this review, the molecular and clinical characteristics (divided according to their clinical utility) of the autoantigens and autoantibodies associated with pSS are discussed.     

TNF-α and Chronic Fatigue Syndrome

Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a retrospective cross-sectional study to examine the role of TNF- in patients with CFS. Our results suggest a significant increase serum TNF- in patients with CFS (P < 0.0001) compared to non-CFS controls. This study supports the further examination of the role of proinflammatory mediators in CFS. Furthermore, the clinical testing of TNF- blockers and other antiinflammatory agents for the treatment of this disease is warranted.     

Trauma and PTSD – An overlooked pathogenic pathway for Premenstrual Dysphoric Disorder?

Summary ¶Background: A recent epidemiological analysis on premenstrual dysphoric disorder (PMDD) in the community revealed increased rates of DSM-IV posttraumatic stress disorder (PTSD) among women suffering from PMDD. Aims: To explore whether this association is artifactual or might have important pathogenic implications. Methods: Data come from a prospective, longitudinal community survey of an original sample of N=1488 women aged 14–24, who were followed-up over a period of 40 to 52 months. Diagnostic assessments are based on the Composite International Diagnostic Interview (CIDI) using the 12-month PMDD diagnostic module. Data were analyzed using logistic regressions (odds ratios) and a case-by-case review. Results: The age adjusted odds ratio between PTSD and threshold PMDD was 11.7 (3.0–46.2) at baseline. 10 women with full PTSD and at least subthreshold PMDD were identified at follow-up. Most reported an experience of abuse in childhood before the onset of PMDD. Some had experienced a life-threatening experience caused by physical attacks, or had witnessed traumatic events experienced by others. 3 women reported more than one traumatic event. Conclusions: A case-by-case review and logistic regression analyses suggest that women with traumatic events and PTSD have an increased risk for secondary PMDD. These observations call for more in-depth analyses in future research.Received March 3, 2003; accepted August 4, 2003 Published online October 22, 2003     

Common circuit or paradigm shift? The functional brain in emotional scene perception and emotional imagery

Meta-analytic and experimental studies investigating the neural basis of emotion often compare functional activation in different emotional induction contexts, assessing evidence for a “core affect” or “salience” network. Meta-analyses necessarily aggregate effects across diverse paradigms and different samples, which ignore potential neural differences specific to the method of affect induction. Data from repeated measures designs are few, reporting contradictory results with a small N. In the current study, functional brain activity is assessed in a large (N = 61) group of healthy participants during two common emotion inductions—scene perception and narrative imagery—to evaluate cross-paradigm consistency. Results indicate that limbic and paralimbic regions, together with visual and parietal cortex, are reliably engaged during emotional scene perception. For emotional imagery, in contrast, enhanced functional activity is found in several cerebellar regions, hippocampus, caudate, and dorsomedial prefrontal cortex, consistent with the conception that imagery is an action disposition. Taken together, the data suggest that a common emotion network is not engaged across paradigms, but that the specific neural regions activated during emotional processing can vary significantly with the context of the emotional induction.     

Similarities between digits’ movements in grasping, touching and pushing

In order to find out whether the movements of single digits are controlled in a special way when grasping, we compared the movements of the digits when grasping an object with their movements in comparable single-digit tasks: pushing or lightly tapping the same object at the same place. The movements of the digits in grasping were very similar to the movements in the single-digit tasks. To determine to what extent the hand transport and grip formation in grasping emerges from a synchronised motion of individual digits, we combined movements of finger and thumb in the single-digit tasks to obtain hypothetical transport and grip components. We found a larger peak grip aperture earlier in the movement for the single-digit tasks. The timing of peak grip aperture depended in the same way on its size for all tasks. Furthermore, the deviations from a straight line of the transport component differed considerably between subjects, but were remarkably similar across tasks. These results support the idea that grasping should be regarded as consisting of moving the digits, rather than transporting the hand and shaping the grip.