Episodic fevers and vasodilatory shock mimicking urosepsis in a patient with HIV-associated multicentric Castleman’s Disease: a case report

Background: Multicentric Castleman's disease (MCD) is a pre-malignancy that presents with lymphadenopathy and features of systemic inflammation. Human immunodeficiency virus (HIV)-associated MCD is associated with human herpesvirus-8 (HHV-8) infection. If untreated MCD has a relapsing and remitting course that is eventually fatal. Case presentation: A 67-year-old man had six hospital admissions over 20 months characterised by fever, urinary frequency and CRP >100 mg/L. The final admission was complicated by hypotension requiring intensive care unit admission and ionotropic support. His history included HIV and Hepatitis B virus (HBV) co-infection on suppressive therapy. Each presentation was managed as presumed urosepsis with use of empirical antibiotics, however numerous blood and urine cultures failed to identify a pathogen. A bone-marrow aspirate and trephine found no evidence of haematological malignancy. A positron emission tomography scan found active lymph nodes, one of which was biopsied and found to contain the plasma-cell variant of Castleman's disease. Ultimately the cause for the recurrent presentations was attributed to progressive MCD. The patient received rituximab monotherapy and has had no further related admissions. Conclusions: MCD should be considered in patients with chronic HIV infection presenting with recurrent sepsis-like episodes and/or vasodilatory shock, particularly if no pathogen is identified or lymphadenopathy is evident

Brief report: how adolescents with ASD process social information in complex scenes. Combining evidence from eye movements and verbal descriptions

We investigated attention, encoding and processing of social aspects of complex photographic scenes. Twenty-four high-functioning adolescents (aged 11–16) with ASD and 24 typically developing matched control participants viewed and then described a series of scenes, each containing a person. Analyses of eye movements and verbal descriptions provided converging evidence that both groups displayed general interest in the person in each scene but the salience of the person was reduced for the ASD participants. Nevertheless, the verbal descriptions revealed that participants with ASD frequently processed the observed person’s emotion or mental state without prompting. They also often mentioned eye-gaze direction, and there was evidence from eye movements and verbal descriptions that gaze was followed accurately. The combination of evidence from eye movements and verbal descriptions provides a rich insight into the way stimuli are processed overall. The merits of using these methods within the same paradigm are discussed

Cerebral toxoplasmosis in a patient with myasthenia gravis and thymoma with immunodeficiency/Good’s syndrome: a case report

Background Patients with thymoma with immunodeficiency (TWI)/Good’s syndrome characteristically have evidence of combined immunodeficiency including low or absent B-cells, hypogammaglobulinemia and defects in T-cell mediated immunity. These patients can present with common or opportunistic infections. Case presentation A 54-year-old female was diagnosed with cerebral toxoplasmosis. This occurred on a background of metastatic thymoma previously treated with chemotherapy and myasthenia gravis (MG) treated with mycophenolate mofetil, monthly intravenous immunoglobulin (IVIG) and pyridostigmine. She reported recurrent herpes zoster infection. The patient had clinical and radiological progression of cerebral infection despite completing standard induction and maintenance therapy with sulfadiazine and pyrimethamine. Investigations found a complete absence of B-cells and evidence for hypogammaglobulinemia which, together with evidence of defects in T-cell mediated immunity and thymoma, lead to a diagnosis of TWI/Good’s Syndrome. The patient has undergone prolonged high-dose therapy for toxoplasmosis and a reduction in immunosuppression with no evidence of recurrent toxoplasmosis or flare of MG. Conclusions TWI/Good’s Syndrome should be suspected in patients with thymoma and recurrent, persistent or unusual infections. If suspected serum immunoglobulins and lymphocyte subsets should be measured. These patients may need closer monitoring, higher dose and prolonged treatment of infections, and weaning of concurrent immunosuppression may be considered.</p

Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells

Abnormalities in CD4+CD25+Foxp3+ regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the α chain of the interleukin-7 receptor, allows an unambiguous flow cytometry–based distinction to be made between CD127lo T reg cells and CD127hi conventional T cells within the CD25+CD45RO+RA− effector/memory and CD45RA+RO− naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25+CD127lo cells comprised 6.35 ± 0.26% of CD4+ T cells, of which 2.05 ± 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127lo phenotype were highly correlated within the CD4+CD25+ population. Moreover, both effector/memory and naive CD25+CD127lo cells manifested suppressive activity in vitro, whereas CD25+CD127hi cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases

Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis

The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC, but not IN-C, was associated with a high proportion of regulatory T cells (Treg). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients compared with IN-NAE in one of two cohorts. UC, but not INCOL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg, reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis

Progressive Activation of CD127+132− Recent Thymic Emigrants into Terminally Differentiated CD127−132+ T-Cells in HIV-1 Infection

AIM: HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation. METHODS: Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured. RESULTS: CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low) and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs. CONCLUSION: The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis

Sensorimotor Difficulties Are Associated with the Severity of Autism Spectrum Conditions

Present diagnostic criteria for autism spectrum conditions (ASC) include social communication and interaction difficulties, repetitive behaviour and movement, and atypical sensory responsivity. Few studies have explored the influence of motor coordination and sensory responsivity on severity of ASC symptoms. In the current study, we explore whether sensory responsivity and motor coordination differences can account for the severity of autistic behaviours in children with ASC. 36 children took part: 18 (13 male, 5 female) with ASC (ages 7-16: mean age 9.93 years) and 18 (7 male, 11 female) typically developing (TD) children (ages 6-12; mean age 9.16 years). Both groups completed a battery of assessments that included motor coordination, sensory responsivity, receptive language, non-verbal reasoning and social communication measures Children with ASC also completed the Autism Diagnostic Observation Schedule and Autism Diagnostic Interview – Revised.. Results showed that children with ASC scored significantly lower on receptive language, coordination and sensory responsivity and a sensorimotor subscale, Modulation of Activity (MoA) compared to the TD group. In the ASC group, MoA significantly predicted ASC severity across all ASC measures; receptive language and sensory responsivity significantly predicted parental reported autism measures; and coordination significantly predicted examiner observed reported scores. Additionally, specific associations were found between the somatosensory perceptive modalities and ASC severity. The results show that sensorimotor skills are associated with severity of ASC symptoms; furthering the need to research sensorimotor integration in ASC and also implying that diagnosis of ASC should also include the assessment of both coordination deficit and atypical sensory responsivity

White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism

The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors

The Edinburgh Social Cognition Test (ESCoT):Examining the effects of age on a new measure of theory of mind and social norm understanding

<div><p>Current measures of social cognition have shown inconsistent findings regarding the effects of healthy aging. Moreover, no tests are currently available that allow clinicians and researchers to examine cognitive and affective theory of mind (ToM) and understanding of social norms within the same test. To address these limitations, we present the Edinburgh Social Cognition Test (ESCoT) which assesses cognitive and affective ToM and inter- and intrapersonal understanding of social norms. We examined the effects of age, measures of intelligence and the Broader Autism Phenotype (BAP) on the ESCoT and established tests of social cognition. Additionally, we investigated the convergent validity of the ESCoT based on traditional social cognition measures. The ESCoT was administered alongside Reading the Mind in Films (RMF), Reading the Mind in Eyes (RME), Judgement of Preference and Social Norm Questionnaire to 91 participants (30 aged 18–35 years, 30 aged 45–60 years and 31 aged 65–85 years). Poorer performance on the cognitive and affective ToM ESCoT subtests were predicted by increasing age. The affective ToM ESCoT subtest and RMF were predicted by gender, where being female predicted better performance. Unlike the ESCoT, better performance on the RMF was predicted by higher verbal comprehension and perceptual reasoning abilities, while better performance on the RME was predicted by higher verbal comprehension scores. Lower scores on inter-and intrapersonal understanding of social norms were both predicted by the presence of more autism-like traits while poorer interpersonal understanding of social norms performance was predicted by increasing age. These findings show that the ESCoT is a useful measure of social cognition and, unlike established tests of social cognition, performance is not predicted by measures of verbal comprehension and perceptual reasoning. This is particularly valuable to obtain an accurate assessment of the influence of age on our social cognitive abilities.</p></div