Harnessing CD8+CD28- Regulatory T Cells as a Tool to Treat Autoimmune Disease.

T regulatory cell therapy presents a novel therapeutic strategy for patients with autoimmune diseases or who are undergoing transplantation. At present, the CD4+ Treg population has been extensively characterized, as a result of defined phenotypic and functional readouts. In this review article, we discuss the development and biology of CD8+ Tregs and their role in murine and human disease indications. A subset of CD8+ Tregs that lack the surface expression of CD28 (CD8+CD28- Treg) has proved efficacious in preclinical models. CD8+CD28- Tregs are present in healthy individuals, but their impaired functionality in disease renders them less effective in mediating immunosuppression. We primarily focus on harnessing CD8+ Treg cell therapy in the clinic to support current treatment for patients with autoimmune or inflammatory conditions.

Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study.

BACKGROUND: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life. OBJECTIVE: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS. METHOD: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility. RESULTS: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels. CONCLUSION: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants.

BackgroundLongitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.MethodsDuring 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUCVL).ResultsThe 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUCVL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were <70 days old.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

Intracranial perineural extension of invasive mycosis: a novel mechanism of disease propagation by Aspergillus fumigatus.

We describe an immunocompetent woman who had refractory, invasive sphenoid sinus Aspergillus fumigatus infection for which there was radiologic evidence of intracranial perineural spread. The patient responded to a combination of antifungal and adjuvant recombinant cytokine therapy.

A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy.

PURPOSE: Comparison of treatment outcome in patients with primary optic nerve sheath meningioma (ONSM). DESIGN: Retrospective, nonrandomized, comparative interventional case series. PARTICIPANTS: Sixty-four patients with at least 50 months of well-documented follow-up. INTERVENTION: Observation, surgery only, radiotherapy only, or surgery and radiotherapy. MAIN OUTCOME MEASURES: Visual acuity expressed as ratio, radiographic progression, and treatment complications. RESULTS: Sixty-four patients (55 women [85.9%] and nine men [14.1%]) were followed for a mean of 150.2 months (range, 51-516 months; standard deviation [SD], 74.7). The mean age at diagnosis was 47.1 years (range, 17-81 years; SD, 15.4). Fifty-eight patients had unilateral disease and six patients had bilateral disease. Of 59 patients with vision greater than no light perception at diagnosis, 13 patients were observed only, 12 had surgery only (four biopsies or partial resections, eight total resections), 18 received radiation alone, and 16 had surgery and radiation (14 biopsies or partial resections and radiation, two total resections and radiation). Irradiated patients received 4000 to 5500 cGy of conventional multiport or conformal external beam therapy, typically fractionated over 6 weeks. Visual acuity measurements at diagnosis among the four groups were not different (ratio, P = 0.186). Visual acuity at diagnosis was > or =0.5 in 56.3%, 0.4 to 0.050 in 12.5%, and <0.050 in 31.3%. Visual acuity measures at last follow-up were different among the four groups (ratio, P = 0.004). At last follow-up the acuity was > or =0.5 in 28.1%, 0.4 to 0.050 in 15.6%, and <0.050 in 56.3%. Visual acuity fell significantly for the observed only (ratio, P = 0.002), surgery only (ratio, P = 0.019), and surgery with radiation groups (ratio, P = 0.030). The radiation only group showed a decrease in visual acuity that was not significant (ratio, P = 0.301). Complication rate was 33.3% in radiation only cases, 66.7% in surgery only cases, and 62.5% in surgery with radiation cases. Twenty-one patients (32.8%) showed radiographic progression. Four patients who were observed, seven patients who had surgery alone, and eight patients who had surgery and radiation developed radiographic progression. Two patients who had radiation alone had radiographic progression before treatment. Only two patients treated with radiation only showed radiographic progression after radiotherapy, and both had at least one surgical procedure before the radiotherapy. CONCLUSIONS: Patients with ONSM receiving radiation alone demonstrated the best visual outcome during the follow-up period. We recommend that fractionated external beam radiation (5000-5500 cGy) be considered as initial treatment in adults in selected cases of ONSM when preservation of visual function is a reasonable therapeutic goal.