Predictors of Relapses or Recurrences in Patients With Giant Cell Arteritis: A Medical Records Review Study.

OBJECTIVE: Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals aged ≥50 years. Its course is marked by a high relapse rate requiring long-term glucocorticoid use with its inherent adverse effects. We aimed to identify factors associated with relapses or recurrences in GCA at diagnosis. METHODS: We reviewed the medical records of consecutive patients with GCA diagnosed between 2009 and 2019 and followed for at least 12 months. We recorded their characteristics at onset and during follow-up. Factors associated with relapses or recurrences were identified using multivariable analysis. RESULTS: We included 153 patients, among whom 68% were female with a median age of 73 (47-98) years and a median follow-up of 32 (12-142) months. Seventy-four patients (48.4%) had at least 1 relapse or recurrence. Headache and polymyalgia rheumatica were the most frequent manifestations of relapses. The first relapse occurred at a median time of 13 months after the diagnosis, with a median dose of 5.5 (0-25) mg/d of glucocorticoids.In multivariable analysis, patients with relapses or recurrences had a higher frequency of cough and scalp tenderness at diagnosis (20.3% vs 5.1%; odds ratio [OR], 4.73; 95% confidence interval [CI], 1.25-17.94; p = 0.022; and 41.9% vs 29.1%; OR, 2.4; 95% CI, 1.07-5.39; p = 0.034, respectively). Patients with diabetes mellitus at diagnosis had fewer relapses or recurrences during follow-up (5.4% vs 19%; OR, 0.24; 95% CI, 0.07-0.83; p = 0.024). CONCLUSIONS: Cough and scalp tenderness at diagnosis were associated with relapses or recurrences, whereas patients with diabetes experienced fewer relapses or recurrences.

Pericardial effusion in giant cell arteritis is associated with increased inflammatory markers: a retrospective cohort study.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequent vasculitis affecting adults aged > 50 years. Cardiac involvement in GCA is considered rare, and only a few cases of pericarditis have been reported. The aim of this study was to determine the characteristics and prognosis of GCA patients suffering from pericardial involvement at diagnosis. METHODS: We conducted a single-centre, retrospective chart review of patients with GCA in internal medicine departments (from 2000 to 2020). Patients were identified through a centralized hospital database. We retrospectively collected demographic, clinicobiological, histological, imaging, treatment and outcome data. Patients with pericardial effusion, defined as an effusion visible on the CT-scan performed at GCA diagnosis were compared to those without pericardial involvement. RESULTS: Among the 250 patients with GCA, 23 patients (9.2%) had pericardial effusion on CT-scan. The comparison between the groups revealed similar distribution of age, gender, cranial symptoms and ocular ischaemic complications. Patients with pericardial effusion had a higher frequency of weight loss. They also had lower haemoglobin levels and higher platelet levels (p = 0.006 and p = 0.002, respectively), and they more frequently had positive temporal artery biopsy. There were no differences concerning the treatment, relapses, follow-up duration or deaths. CONCLUSIONS: This case series sheds light on GCA as a cause of unexplained pericardial effusion or symptomatic pericarditis among adults aged > 50 years and elevated inflammatory biological markers. Fortunately, pericardial involvement is a benign GCA manifestation. In that context, the search for constitutional symptoms, cranial symptoms and associated signs of polymyalgia rheumatica is crucial for rapidly guiding GCA diagnosis.

Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD).

Endothelial dysfunction is a key factor in atherosclerosis. However, the link between endothelial repair and severity of atherosclerotic cardiovascular disease (ASCVD) is unclear. This study investigates the relationship between ASCVD, markers of inflammation, and circulating endothelial progenitor cells, namely hematopoietic cells with paracrine angiogenic activity and endothelial colony forming cells (ECFC). Two hundred and forty-three subjects from the TELARTA study were classified according to the presence of clinical atherosclerotic disease. ASCVD severity was assessed by the number of involved vascular territories. Flow cytometry was used to numerate circulating progenitor cells (PC) expressing CD34 and those co-expressing CD45, CD34, and KDR. Peripheral blood mononuclear cells ex vivo culture methods were used to determine ECFC and Colony Forming Unit- endothelial cells (CFU-EC). The ECFC subpopulation was analyzed for proliferation, senescence, and vasculogenic properties. Plasma levels of IL-6 and VEGF-A were measured using Cytokine Array. Despite an increased number of circulating precursors in ASCVD patients, ASCVD impaired the colony forming capacity and the angiogenic properties of ECFC in a severity-dependent manner. Alteration of ECFC was associated with increased senescent phenotype and IL-6 levels. Our study demonstrates a decrease in ECFC repair capacity according to ASCVD severity in an inflammatory and senescence-associated secretory phenotype context.

Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model.

RATIONALE: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue. OBJECTIVE: We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. METHODS AND RESULTS: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. CONCLUSIONS: This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941.

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R2 = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease.

OBJECTIVES: We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). METHODS: Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. RESULTS: KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10-4) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10- 4). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. CONCLUSIONS: Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Contribution of anti-ß2glycoprotein I IgA antibodies to the diagnosis of anti-phospholipid syndrome: potential interest of target domains to discriminate thrombotic and non-thrombotic patients.

OBJECTIVES: Although the last international guidelines for aPL recommended determination of IgA aCL and anti-ß2glycoprotein I (aß2GPI) antibodies for the evaluation of APS in the absence of conventional IgG or IgM aCL and aß2GPI antibodies, the clinical value of these antibodies remains controversial. We evaluated the clinical utility of IgA aPL and of the determination of target domains of aß2GPI IgA antibodies. METHODS: A retrospective analysis was performed on sera from 439 patients referred for routine detection of aPL IgA by in-house ELISA. Sera positive for aß2GPI IgA were subsequently tested for aß2GPI domain 1 (D1) and domain 4/5 (D4/5) antibodies using ELISAs. RESULTS: The prevalence of aß2GPI IgA antibodies was 16% in patients, significantly different from controls (1%, P < 0.0001). These antibodies were associated with clinical contexts related to APS as thrombosis (28.6% vs. 15%, P = 0.009) and SLE (42% vs. 15%, P < 0.0001). Interestingly, determination of their target domains revealed a significant association between aß2GPI IgA directed against D4/5 and SLE without thrombosis (66.7 vs. 16.7%, P = 0.002). In contrast, aCL IgA were not more prevalent in patients than in controls. CONCLUSION: Our study confirmed the interest of aß2GP1 IgA in the exploration of APS and suggests that identification of target domains of aß2GP1 IgA may be useful in the evaluation of thrombotic risk in SLE patients.

Glossopharyngeal insufflation and breath-hold diving: the more, the worse?

OBJECTIVE: The glossopharyngeal insufflation maneuver (lung packing) is largely performed by competitive breath-hold divers to improve their performance, despite observational evidence of fainting and loss of consciousness in the first seconds of apnea. METHODS: We describe here the time course of hemodynamic changes, induced by breath-holding with and without lung packing, in 2 world-class apnea competitors. RESULTS: When compared with apnea performed after a deep breath (100% vital capacity), lung packing leads to a decrease in cardiac output, blood pressure, and cerebral blood flow during the first seconds after the beginning of apnea. The major hemodynamic disorders were observed in diver 1, who exhibited the greater increase in pulmonary volume after lung packing (+22% for diver 1 vs +10% for diver 2). After the initial drop in both cardiac output and blood pressure, the time course of hemodynamic alterations became quite similar between the two apneas. CONCLUSIONS: Some recommendations, such as limiting the number of maneuvers and performing lung packing in the supine position, should be expressed to avoid injuries secondary to the use of glossopharyngeal insufflation.

Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

Herpetic encephalitis: which treatment for which body weight?

BACKGROUND: Prognosis of herpetic encephalitis remains severe, with a high proportion of deaths and sequelae. Its treatment is based on acyclovir, but the precise and most effective modalities of this treatment are not established. The objective of this study was to determine them. METHODS: For this, we carried out a descriptive, retrospective, monocentric study, using the current coding database at Marseille University Hospitals. Cohort was intended to be exhaustive for the disease, from January 2000 to June 2019, including patients hospitalized in intensive care and conventional hospitalization sector. Patients (n = 76) included were at least 16 years of age and had a clinical presentation, cerebral Magnetic Resonance Imaging, and/or electroencephalogram abnormalities consistent with herpetic encephalitis confirmed by a positive HSV-PCR in the CSF. Clinical data and treatment, including the doses actually administered to the patient, were compared according to patient's outcome. RESULTS: The mortality rate was 12%, whereas 49% had complete recovery and 39% sequelae impeding independence. Poor outcome was statistically associated with persistence of confusion, aphasia, and impaired consciousness lasting more than 5 days, superinfection, status epilepticus, and length of stay in intensive care unit. A statistical decision tree, constructed using the Classification And Regression Tree model, to prioritize treatment management, showed two main factors that influence the outcome: the patient's weight, and the average daily acyclovir dose actually administered. CONCLUSION: These results suggest to modify acyclovir management in herpetic encephalitis, for low-weight patients (< 79 kg) with a minimum dosage of 2550 mg/day (850 mg/ 8 h), when possible.

Incidence, risk profile and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery.

PURPOSE: We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism. MATERIALS AND METHODS: A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation. Potential variables predictive of venous thrombosis were analyzed. RESULTS: Complete data were available in 538 patients (463 male and 75 female), of whom 177 underwent nephrectomy, 86 radical cystectomy and 275 radical prostatectomy. A total of 40 deep venous thrombosis cases were found (7.4%), most of which were asymptomatic (92%) and limited to deep calf veins (80%). Of those asymptomatic deep venous thrombosis cases 86% were limited to deep calf veins. In all, 12 pulmonary embolisms were diagnosed, of which 4 were lethal. On multivariate analysis history of venous thromboembolism (OR 5.16, p = 0.02) and radical cystectomy (OR 3.47, p = 0.002) were independently associated with venous thromboembolism. CONCLUSIONS: Lower extremity venous thromboembolism has a high rate of occurrence after urological surgery for cancer despite the recommended venous thromboembolism prophylaxis. Most cases are asymptomatic and limited to deep calf veins. Our results suggest that complete lower limb ultrasound should be performed early after radical cystectomy and in patients with a personal history of venous thromboembolism.

Relevance of systematic anti-nuclear antibodies testing after obstetrical complications.

Adverses pregnancy outcomes are commonly encountered with autoimmune disease (AID). Although anti-nuclear antibodies (ANA) are often present several years before AID diagnosis, the importance of ANA testing has not been evaluated in this context. The objective of this study was to determine if ANA discovery after obstetrical complications is associated with a diagnosis of AID and improves the prognosis of subsequent pregnancies. All patients presented at the multidisciplinary board meeting (MBM) "Thrombophilia and Pregnancy", whose ANA were discovered after an obstetrical complication, were included in a multicenter descriptive study. All patients were referred to an internal medicine consultation for diagnosis. Data were collected retrospectively by computer chart analysis and updated by phone. A total of 404 patients were included, of which 50 (12.4 %) had a diagnosis of AID related to ANA. Patients with AID had higher ANA levels (p < 0.001), with more frequent specificity (26%, versus 6.7%, p < 0.0001), and more often persistent (84% versus 30.8%, p < 0.0001) compared to patients without AID. Subsequent pregnancy outcomes were not significantly affected by ANA levels and AID diagnoses. Our study shows that the discovery of ANA after obstetrical complications may lead to an early diagnosis of AID. It makes us reconsider the systematic determination of ANA after an obstetrical event because in the case where ANA are found positive, an adapted follow-up would reduce the negative impact of ANA presence on subsequent pregnancies.

Quantification of Antifibrillarin (anti-U3 RNP) Antibodies: A New Insight for Patients with Systemic Sclerosis.

BACKGROUND: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. METHODS: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. RESULTS: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. CONCLUSIONS: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

Characteristics of patients with systemic sclerosis suffering from a lower limb amputation: Results of a French collaborative study.

Objective: Systemic sclerosis mainly affects the microvascular network. However, macrovascular manifestations have been reported. We aimed to investigate the characteristics of systemic sclerosis patients with an amputation of a lower limb segment. Methods: We designed a retrospective, case-control, multicentric study on systemic sclerosis patients with amputation of a lower limb segment secondary to critical ischemia via the French Research Group on Systemic Sclerosis. For each case, a control (systemic sclerosis patient without lower limb symptom) was matched with sex, age (±5 years), and cutaneous subset of systemic sclerosis. Results: In total, 26 systemic sclerosis patients (mean age of 67.2 ± 10.9 years, 20 females, 21 limited cutaneous forms) with a lower limb amputation and 26 matched controls (mean age of 67.3 ± 11.2 years, 20 females, 22 limited cutaneous forms) were included. At the time of amputation, the mean disease duration was 12.8 (±8.6) years. In comparison to controls, systemic sclerosis patients with amputation had more digital ulcers (p = 0.048), history of digital ulcers (p = 0.026), and a higher prevalence of pulmonary arterial hypertension (p = 0.024). Systemic sclerosis patients with amputation were more often smokers (p = 0.008) and under corticosteroids (p = 0.015). In the multivariate model, pulmonary arterial hypertension, smoking status, and corticosteroids were independent markers associated with lower limb amputation in systemic sclerosis. In the follow-up, 10 patients (38.5%) had recurrent ischemia requiring a new limb amputation, and five patients (19.2%) had an amputation of the contralateral limb. Conclusion: This study identifies some markers associated with lower limb amputation in systemic sclerosis such as digital ulcers and pulmonary arterial hypertension and points out the high risk associated with tobacco consumption and corticosteroid use.

Arterial compliance in divers exposed to repeated hyperoxia using rebreather equipment.

BACKGROUND: Acute hyperoxic exposure is known to modify cardiovascular parameters like a decrease in cardiac output, arterial vasoconstriction, and autonomic nervous system changes. We hypothesized that repeated hyperbaric hyperoxic exposures, as experienced by military oxygen divers, lead to long-term arterial alterations. METHODS: Arterial blood pressure measurements and pulse wave velocity (PWV) recordings were performed during basal conditions in 15 elite military oxygen divers, and compared to 15 non-diver controls. The two groups were matched appropriately for physical characteristics (age: 35 +/- 5 yr, weight: 77 +/- 8 kg, height: 177 +/- 6 cm, body mass index: 24.6 +/- 2.0 kg x m(-2)), and aerobic capacity (VO2max : 52 +/- 7 ml x min(-1) x kg(-1)). RESULTS: No significant difference was found in systolic blood pressure (120 +/- 11 mmHg), diastolic blood pressure (70 +/- 8 mmHg), or pulse pressure (50 +/- 7 mmHg). Furthermore, there was no significant difference in the carotid-femoral PWV (6.7 +/- 0.9 m x s(-1)), the carotid-radial PWV (8.7 +/- 1.7 m x s(-1)), or the carotid-pedal PWV (8.1 +/- 1.1 m x s(-1)) between divers and controls. CONCLUSION: No difference in arterial compliance was observed in physically well-trained military oxygen divers in comparison with matched controls.

Heart rate recovery improves after exercise in water when compared with on land.

BACKGROUND: Water immersion has demonstrated its effectiveness in the recovery process after exercise. This study presents for the first time the impact of water immersion on heart rate recovery after low-intensity cycle exercise. METHODS: Sixteen male volunteers were involved in the study. The experiment consisted of two cycling exercises: 1 h in ambient air and 1 h in water (temperature: 32 ± 0·2°C). The exercise intensity was individually prescribed to elicit around 35%-40% of VO2 peak for both conditions. Heart rate recovery was analysed according to recognized methods, such as the differences between heart rate at exercise completion and within the 2 min recovery period. RESULTS: Although the two exercises were performed both at same energy expenditure and heart rate, the indexes used to assess the fast and slow decay of the heart rate recovery were significantly shortened after exercise in water. CONCLUSION: The results of the present study suggest that cycling in thermoneutral water decreases the cardiac work after exercise when compared with cycling on land.

Natural Killer Cells Exhibit a Peculiar Phenotypic Profile in Systemic Sclerosis and Are Potent Inducers of Endothelial Microparticles Release.

The pathophysiology of systemic sclerosis (SSc) involves early endothelial and immune activation, both preceding the onset of fibrosis. We previously identified soluble fractalkine and circulating endothelial microparticles (EMPs) as biomarkers of endothelial inflammatory activation in SSc. Fractalkine plays a dual role as a membrane-bound adhesion molecule expressed in inflamed endothelial cells (ECs) and as a chemokine involved in the recruitment, transmigration, and cytotoxic activation of immune cells that express CX3CR1, the receptor of fractalkine, namely CD8 and γδ T cells and natural killer (NK) cells. We aimed to quantify circulating cytotoxic immune cells and their expression of CX3CR1. We further investigated the expression profile of NK cells chemokine receptors and activation markers and the potential of NK cells to induce EC activation in SSc. We performed a monocentric study (NCT 02636127) enrolling 15 SSc patients [15 females, median age of 55 years (39-63), 11 limited cutaneous form and 4 diffuse] and 15 healthy controls. Serum fractalkine levels were significantly increased in SSc patients. Circulating CD8 T cells numbers were decreased in SSc patients with no difference in their CX3CR1 expression. Circulating γδ T cells and NK cells numbers were preserved. CX3CR1 expression in CD8 and γδ T cells did not differ between SSc patients and controls. The percentage and level of CX3CR1 expression in NK cells were significantly lowered in SSc patients. Percentages of CXCR4, NKG2D, CD69-expressing NK cells, and their expression levels were decreased in NK cells. Conversely, CD16 level expression and percentages of CD16+ NK cells were preserved. The exposure of human microvascular dermic EC line (HMVEC-d) to peripheral blood mononuclear cells resulted in similar NK cells degranulation activity in SSc patients and controls. We further showed that NK cells purified from the blood of SSc patients induced enhanced release of EMPs than NK cells from controls. This study evidenced a peculiar NK cells phenotype in SSc characterized by decreased chemokine and activation receptors expression, that might reflect NK cells involvement in the pathogenic process. It also highlighted the role of NK cells as a potent mechanism inducing endothelial activation through enhanced EMPs release.