• B7-H6 transcripts, B7-H6 cell-surface expression, and sB7-H6 can be induced in inflammatory conditions in vitro and in vivo.• B7-H6 is expressed on proinflammatory CD141 CD16 1 monocytes in sepsis conditions and is linked to an increased mortality.B7-H6, a member of the B7 family of immunoreceptors, is as a cell-surface ligand for the NKp30-activating receptor expressed on natural killer cells. B7-H6 is not detected in normal human tissues at steady state but is expressed on tumor cells. However, whether B7-H6 can be expressed in other conditions remains unknown. We analyzed here the pathways that lead to the expression of B7-H6 in nontransformed cells. In vitro, B7-H6 was induced at the surface of CD14 1 CD16 1 proinflammatory monocytes and neutrophils upon stimulation by ligands of Toll-like receptors or proinflammatory cytokines such as interleukin-1b and tumor necrosis factor a. In these conditions, a soluble form of B7-H6 (sB7-H6) was also produced by activated monocytes and neutrophils. In vivo, B7-H6 was expressed on circulating proinflammatory CD14 1 CD16 1 monocytes in a group of patients in sepsis conditions, and was linked to an increased mortality. sB7-H6 was selectively detected in the sera of patients with gram-negative sepsis and was associated with membrane vesicles that co-sedimented with the exosomal fraction. These findings reveal that B7-H6 is not only implicated in tumor immunosurveillance but also participates in the inflammatory response in infectious conditions. This trial was registered at www.clinicaltrials.gov as #NTC00699868. (Blood. 2013;122(3):394-404)

Objective. To assess the mortality profile of systemic lupus erythematosus (SLE) patients in France using multiple-cause-of-death analysis.Methods. Data were collected between 2000 and 2009 in the French Epidemiological Center for the Medical Causes of Death database, and death certificates issued upon the death of an adult for whom SLE was an underlying cause of death (UCD) or a nonunderlying cause of death (NUCD) were evaluated using multiple-cause-of-death analysis. Sex, age, sex ratio, standardized mortality rates, as well as frequency of the various causes of death were assessed, at both a national and a regional level. For the main causes of death, the observed number of deaths in relation to the expected number of deaths (O:E ratio) (standardized for age and sex) was calculated.Results. During the study period, 1,593 deaths related to SLE were identified. The mean ؎ SD age at death was 63.5 ؎ 18.4 years and the sex ratio (female: male) was 3.5. The mean standardized mortality rate was 3.2 per 1 million people (range 2.7-4.1). When SLE was the UCD (n ‫؍‬ 637), the main NUCDs were cardiovascular diseases (49.5%), infectious diseases (24.5%), and renal failure (23.2%). When SLE was an NUCD (n ‫؍‬ 956), the most common UCDs were cardiovascular diseases (35.7%), neoplasms (13.9%), and infectious diseases (10.3%). The overall O:E ratio was >1 for infectious and cardiovascular diseases and renal failure (especially among people <40 years of age for the latter 2 causes), but was <1 for neoplasms.Conclusion. Cardiovascular disease is the leading cause of death associated with SLE in France.Systemic lupus erythematosus (SLE) is a rare systemic autoimmune disease (1). The overall mortality rate among patients with SLE has improved dramatically over the past 50 years: the 5-year survival rate was ϳ50% in the 1950s, and it has increased worldwide to Ͼ90% since the 1990s. Nevertheless, the mortality rate is still higher among SLE patients than among the general population, with standardized mortality ratios of 2-5 in epidemiologic studies (2-13).Causes of death among SLE patients include active SLE, infections, cancer, renal failure, cardiovascular events, and non-SLE-related conditions. A bimodal distribution of mortality in SLE has been reported, with a first peak within the first year after diagnosis, mostly attributable to active disease and infections, and a second peak occurring later and mainly due to cardiovascular events (14). Yet, this distribution is not universally observed (15), and the exact burden of each cause of mortality varies across studies (available online at http://fr.ap-hm.fr/sites/default/files/ mortalup_supplements.pdf).Although recent studies have shown that infections are the main cause of death in SLE, others have demonstrated that cardiovascular diseases are a new leading cause (2-16). These discrepancies may be due to methodologic limitations. Indeed, available published data are mostly from single-center cohorts of limited size and/or with short followup duration, with only a few events ...

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