Specific Follicular Helper T Cell Signature in Takayasu Arteritis.

OBJECTIVE: Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS: Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS: Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/ß TCR repertoire. CONCLUSION: We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

[Aging of the immune system: From fundamental to clinical data]. / Le vieillissement du système immunitaire : du fondamental à la clinique.

Major progress in preventing, delaying or curing various pathologies normally encountered in old age results in a continuous improvement in life expectancy. However, understanding the underlying cause of the disparate comorbidities occurrence with aging remains a priority in order to propose adapted care for the older population. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, and is associated with pro-inflammatory environment. In another hand, stressful events (acute or chronic) can also impact the immune system through the secretion of hormones, which are also altered with aging. Blooming evidences from psychoneuroimmunology field suggest that, in acute medical conditions, elderly people are not equal in their responses to stressors depending on many extrinsic and intrinsic parameters. These factors could interfere with elderly's ability to mount an effective immune response. The objective of this review is to provide an overview of the literature (from fundamental to clinical observations) to draw a global picture of immunosenescence. Understanding this process could enable us to target fundamental age-related pathways and thus open new avenues in improving both lifespan and health span.

INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema.

PURPOSE: To compare the efficacy of infliximab and adalimumab in patients with refractory uveitis-related macular edema (ME). METHODS: A retrospective study was conducted in all patients with refractory uveitis-related ME treated with infliximab or adalimumab in Pitié-Salpêtrière hospital between January 1, 2006 and January 1, 2016. All patients underwent a complete ophthalmologic examination, OCT and retinal angiography at baseline, and 6 (M6) and 24 months (M24) after treatment initiation. Main outcome was a decrease in central foveal thickness (CFT) on OCT. RESULTS: Twenty-five patients were included: 12 treated with adalimumab and 13 treated with infliximab. The median baseline CFT was 381 µm (Q1 = 254; Q3 = 470) in the adalimumab group and 469 µm (307; 539) in the infliximab group. At M6, 6/12 adalimumab-treated patients (50%) and 8/13 infliximab-treated patients (61%) were responders. The median CFT decrease from baseline was 61 µm (17-136) and 66 µm (-59-119) respectively at M6 and M24 in the adalimumab group versus 92 µm (9-165) and 52 µm (33-130) respectively at M6 and M24 in the infliximab group (all p > 0.05). CONCLUSION: No significant difference in efficacy was observed between infliximab and adalimumab at M6 and M24.

Management of severe complications in Behçet's disease with TNF inhibitors.

INTRODUCTION: The efficacy of anti-TNFα agents has been recently evaluated in many studies in Behçet's disease (BD), particularly in ocular and life-threatening manifestations such as neurological and vascular disease. Areas covered: The following article aims to summarize the currently available efficacy and safety data of anti-TNFα agents in BD. Expert opinion: Most studies have shown dramatic and rapid efficacy with anti-TNFα agents on the main BD-associated issues including posterior uveitis, gastro-intestinal and neurological complications as well as major vessel disease. Experts in the field do recommend the use of anti-TNF agents (either infliximab or adalimumab) as a first-line therapy in severe posterior uveitis in BD and now use anti-TNFα treatment in BD-associated life threatening manifestations. However, data is mainly based on retrospective cohorts or open-label prospective studies. Controlled studies (versus conventional immunosuppressants such as azathioprine and cyclophosphamide) are warranted to properly evaluate their efficacy as first line therapeutic in life-threatening manifestations of BD.

[Elderly patients and intensive care: Systematic review and geriatrician's point of view]. / Réanimation du sujet âgé : revue de la littérature et point de vue du gériatre.

The global population is aging and intensive care unit admission rate of elderly patients is dramatically increasing. The objective of this review is to provide an overview of the literature about the management of elderly patients in intensive care unit and more specifically about epidemiology, admission criteria, mortality, functional prognosis and ethical aspects. We also discuss the data on cardiorespiratory arrest, shock, acute respiratory failure and delirium. The mortality rate of patients over 80 years old in intensive care unit can reach up to 70% at 1year, but is dependent on many factors, such as comorbidities or frailty. Above all, more than half of elderly patients recover their long-term autonomy. Their quality of life is comparable to that of the same age population. Considering that the first 3months after an intensive care unit stay are the most decisive in terms of vital and functional prognosis, we will discuss strategies to improve care through the creation of dedicated intensive care-geriatrics networks.

Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).

Health effects of low-level exposure to polychlorinated biphenyls.

A polychlorinated biphenyl (PCB) spill resulting from a transformer explosion in Syracuse, New York, with no subsequent fire, provided an opportunity for the examination of the effects of low-level PCB exposure without the confounding presence of furans and dioxins. The incident provided 52 individuals exposed to PCB among building personnel, police, firemen, and public utility employees. Sixty-eight nonexposed were matched to the exposed group by sex, age, employer, and job description. Data were collected on the exposed relative to their activities at the spill site, their location, possible routes of exposure, duration of exposure, and subsequent health effects. Exposed and nonexposed were interviewed for past medical history and relevant symptoms. Blood chemistries were studied inclusive of SGOT, SGPT, total protein, CBC, cholesterol, and triglyceride levels, as well as a fasting blood PCB level measurement. Six weeks after the spill, exposed and nonexposed were reinterviewed and had their blood work repeated except for the CBC and PCB levels. Exposed and nonexposed laboratory results were unremarkable. Some transient skin irritation believed to be associated with PCBs was noted. There were significant PCBs in blood level trends for occupation, age, duration of exposure, and level of alcohol consumption. Triglyceride level was highly correlated with PCB level. This relationship held when age and alcohol consumption were controlled for.