Outcome and prognosis of isolated carotid vasculitis.

OBJECTIVE: To assess the prognosis and outcome of patients with isolated carotid vasculitis. METHODS: We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27-45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu). RESULTS: The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12-96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. > 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. >70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis. CONCLUSION: Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.

Efficacy of anti-TNF alpha in severe and refractory major vessel involvement of Behcet's disease: A multicenter observational study of 18 patients.

OBJECTIVE: To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behçet's disease (BD). METHODS: A multicenter study evaluating 18 refractory BD patients with major vessel involvement [pulmonary artery (n = 4), aorta (n = 4) or peripheral artery aneurysm (n = 1) and/or pulmonary artery (n = 7), inferior vena cava (n = 5), or intra-cardiac (n = 3) thrombosis or Budd Chiari Syndrome (n = 2)] treated with anti-TNFα agents. RESULTS: Vascular remission was achieved in 16 (89%) patients. The 9 months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy [OR = 8.7 (1.42-62.6), p = 0.03]. The median daily dose of corticosteroids significantly decreased at 12 months. Side effects included infection (n = 4) and pulmonary edema (n = 1). CONCLUSION: TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9 months compared to conventional immunosuppressants in BD patients with major vessels disease.

mTOR pathway activation in large vessel vasculitis.

BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown. METHODS: We evaluate mTORC pathway activation in vascular aorta lesions and in T cell homeostasis of patients with LVV. RESULTS: Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway (S6RP phosphorylation). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. mTORC1 activation was found also in Th1 and Th17 cells both systemically and in inflamed vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNγ+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV. CONCLUSIONS: We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.

Can anticoagulation therapy in cerebral venous thrombosis associated with Behçet's disease be stopped without relapse?

There is as yet no consensus on the treatment of cerebral venous thrombosis (CVT) in Behçet's disease, and the place of anticoagulation is also still being debated. This report is of a series of seven patients with Behçet's disease (BD)-associated CVT, for which anticoagulation was stopped, and discusses the possibility of stopping anticoagulation during follow-up while receiving optimal treatment for BD. The diagnosis of BD was established during follow-up, which lasted a median of 120 [range: 60-1490] days after CVT diagnosis. The median duration of anticoagulation therapy was 29.5 months. On stopping anticoagulation, concomitant treatment then included colchicine, steroids and azathioprine, all introduced after BD was diagnosed. With a median follow-up of 25 months after anticoagulation interruption, only one relapse of CVT was observed. No relapse of CVT or other venous thrombosis was observed in the six patients treated by steroids associated with an immunosuppressant or colchicine. Our results emphasize that corticosteroids are essential for the treatment of BD-associated CVT, and that anticoagulant therapy may be safely stopped during follow-up in the presence of optimal BD treatment (steroids alone or with immunosuppressive drugs).

Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.

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).

Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.

OBJECTIVE: Primary Sjögren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non-Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS. METHODS: B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay. RESULTS: We observed an expansion of an unusual CD21-/low B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21-/low B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21-/low B cells from patients with primary SS remained responsive to Toll-like receptor (TLR) stimulation. Molecules specifically expressed in CD21-/low B cells that are likely to induce their unresponsive stage were detected in gene array analyses. CONCLUSION: Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.

Immunosuppressants reduce venous thrombosis relapse in Behçet's disease.

OBJECTIVE: To investigate and describe the long-term outcome of venous thrombosis in patients with Behçet's disease (BD). METHODS: In a retrospective cohort of 807 BD patients, a reported 296 patients (36.7%) (73.3% male, median age 30 years [interquartile range 24-36 years]) met the international classification criteria for BD and had venous thrombosis. We assessed factors associated with thrombosis relapse and mortality. RESULTS: There were a total of 586 venous thrombosis events, including 560 cases of deep thrombosis and 26 cases of superficial thrombosis. Deep venous thrombosis events included 323 cases of limb thrombosis (55.1%), 77 cases of cerebral venous thrombosis (13.1%), 57 cases of pulmonary embolism (9.7%), 63 cases of vena cava lesions (10.7%), 14 cases of Budd-Chiari syndrome (2.4%), and 13 cases of cervical vein thrombosis (2.2%). One hundred of 296 patients (33.8%) experienced at least 1 venous thrombosis relapse. The mortality rate was 6.4% (19 of 296 patients) after a median followup of 4.75 years (interquartile range 2-7 years). In univariate analysis, death was associated with cardiac involvement (P = 0.026) and Budd-Chiari syndrome (P = 0.004). In multivariate analysis, the use of immunosuppressive agents was found to prevent relapse of venous thrombosis (hazard ratio 0.27 [95% confidence interval 0.14-0.52], P = 0.00021), and there was a trend toward prevention of relapse with the use of glucocorticoids (hazard ratio 0.62 [95% confidence interval 0.40-0.97], P = 0.058). CONCLUSION: Immunosuppressive agents significantly reduce venous thrombosis relapse in BD.

[Neurological involvement of sarcoidosis: current diagnostic and therapeutic strategies]. / Atteinte neurologique de la Sarcoïdose : stratégies diagnostiques et thérapeutiques actuelles.

Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20-30%) and more rarely peripheral neuropathy (approximately 10-15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse.

Behçet's disease uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

French recommendations for the management of non-infectious chronic uveitis.

This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.

Evolution of biomarkers of liver fibrosis and liver insufficiency in hepatitis C virus-infected patients treated with pegylated interferon plus ribavirin and rituximab.

Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count.

[Thoracic manifestations of Behcet's disease]. / Atteintes thoraciques de la maladie de Behçet.

Behcet's disease (BD) is a multisystemic vasculitis involving arteries and veins of all sizes. While joint and dermatological manifestations are the most common features of BD and are associated with a good prognosis; vascular involvement, remains the principal cause of death. Arterial manifestations occur in 5-10% of cases and manifest as occlusion/thrombosis or aneurysms. Arterial aneurysms are likely multiple and the most common sites are pulmonary arteries, aorta and arteries of lower limbs. Parenchymal involvement is less frequent and may manifest as consolidation or nodules, which may evolve to excavation. Aneurysms may occur at the sites of arterial puncture; then, non-traumatic techniques are favored. Patients with arterial manifestations may present with fever and increased inflammatory markers. Artery damage is rare, serious, and may result in massive hemoptysis. The prognosis of pulmonary artery aneurysms is severe (mortality estimated up to 26%) but has been improved by earlier diagnosis and the introduction of immunosuppressants. Treatment of severe arterial manifestations is based on high-dose corticosteroids along with cyclophosphamide or anti-TNF antagonists. Anticoagulation could be added to immunosuppressants in case of venous thrombosis if a coexisting pulmonary aneurysm is ruled out. Endovascular treatment should be performed in case of severe symptomatic pulmonary aneurysms, along with an adequate medical management. Long-term maintenance therapy of these severe forms is of paramount importance because of relapse risk (40% at five years).

[Cardiac sarcoidosis: Diagnosis, prognosis and therapeutics]. / Sarcoïdose cardiaque : stratégies diagnostiques et thérapeutiques actuelles.

Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach.

Mortality in Behçet's disease.

OBJECTIVE: To report the long-term mortality in patients with Behçet's disease (BD). METHODS: A cohort of 817 patients fulfilling the international criteria for BD from a single center in France were analyzed for causes of death, the standardized mortality ratio (SMR), and the factors associated with mortality. RESULTS: Among the 817 patients with BD, 41 (5%) died after a median followup of 7.7 years, of whom 95.1% were male. The mean ± SD age at death was 34.8 ± 11.9 years. Main causes of death included major vessel disease (mainly, arterial aneurysm and Budd-Chiari syndrome) (43.9%), cancer and malignant hemopathy (14.6%), central nervous system involvement (12.2%), and sepsis (12.2%). The mortality rate at 1 year and 5 years was 1.2% and 3.3%, respectively. There was an increased mortality among patients ages 15-24 years (SMR 2.99, 95% confidence interval [95% CI] 1.54-5.39) and those ages 25-34 years (SMR 2.90, 95% CI 1.80-4.49) as compared with age-and sex-matched healthy controls. The mortality decreased in patients older than age 35 years (SMR 1.23, 95% CI 0.75-1.92). In multivariate analyses, male sex (hazard ratio [HR] 4.94, 95% CI 1.53-16.43), arterial involvement (HR 2.51, 95% CI 1.07-5.90), and a high number of BD flares (HR 2.37, 95% CI 1.09-5.14) were independently associated with the risk of mortality. CONCLUSION: The overall mortality in our BD cohort was 5% after a median followup of 7.7 years. Male sex, arterial involvement, and the number of flares were associated with mortality in BD.

[Observational study of QuantiFERON® management for ocular tuberculosis diagnosis: Analysis of 244 consecutive tests]. / Étude observationnelle de l'usage du QuantiFERON® pour le diagnostic de tuberculose oculaire, basée sur 244 tests consécutifs.

INTRODUCTION: Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis. PATIENTS AND METHODS: Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging. RESULTS: Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis. CONCLUSION: Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.

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.

La fibrose rétropéritonéale idiopathique.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibro-inflammatory tissue around the aorta entrapping the adjacent structures. RPF can be idiopathic or secondary to many disorders. The physiopathology is unknown but can be part of the spectrum of IgG4 related diseases. Imaging studies and inflammatory markers are essential for initial evaluation and follow-up. Biopsy is usually not recommended. The first line of treatment is corticosteroids associated or not with immunosuppressive drugs. In case of ureteral obstruction with renal failure, ureteral stent placement or nephrostomies are recommended. Initial response to treatment is usually good but relapses are frequent.

[Review on anti-glomerular basement membrane disease or Goodpasture's syndrome]. / Mise au point sur la maladie des anticorps anti-membrane basale glomérulaire ou syndrome de Goodpasture.

Anti-glomerular basement membrane (anti-GBM) disease or Goodpasture's syndrome is a small vessel vasculitis affecting the capillary beds of kidneys and lungs. It is an autoimmune disease mediated by autoantibodies targeting the glomerular and alveolar basement membranes, leading to pneumorenal syndrome. It is a rare, monophasic and severe disease, associating rapidly progressive glomerulonephritis and alveolar hemorrhage. The presence of antineutrophil cytoplasmic antibodies (ANCA) is reported in 20 to 60% of cases. Management should be prompt and combine plasma exchange with systemic corticosteroids and immunosuppressive therapy by cyclophosphamide. The objective of this review is: 1) to describe the pathogenesis, clinical and histological features of the disease; 2) to characterize double-positive anti-GBM/ANCA patients; 3) to highlight the prognostic factors of renal and global survival, and 4) to focus on the treatment of anti-GBM disease.