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This essay ponders over the dismissal of reading practices and theories that were linked to the modernist shift from ‘literature’ to ‘writing’ ( écriture) in the second half of the twentieth century. It provides an intellectual genealogy of the rise and fall of the writing/reading couple, before going on to consider the cultural effects – as well as the educational and institutional consequences in academia – of the challenge to literature’s ‘cultural difference’ mounted by both cognitivist and culturalist approaches to literature, in their turn away from or against ‘language’.

Reliable immunoassays are essential to early predict and monitor vaccine efficacy against SARS-CoV-2. The performance of an Interferon Gamma Release Assay (IGRA, QuantiFERON® SARS-CoV-2), and a current anti-spike serological test, compared to a plaque reduction neutralization test (PRNT) taken as gold standard were compared. Eighty vaccinated individuals, whose 16% had a previous history of COVID-19, were included in a longitudinal prospective study and sampled before and two to four weeks after each dose of vaccine. In non-infected patients, 2 doses were required for obtaining both positive IGRA and PRNT assays, while serology was positive after one dose. Each dose of vaccine significantly increased the humoral and cellular response. By contrast, convalescent subjects needed a single dose of vaccine to be positive on all 3 tests. Both IGRA and current serology assay were found predictive of a positive titer of neutralizing antibodies that is correlated with vaccine protection. Patients over 65 or 80 years old had a significantly reduced response. The response tended to be better with the heterologous scheme (vs. homologous) and with the mRNA-1273 vaccine (vs. BNT162b2) in the homologous group, in patients under 55 and under 65 years old, respectively. Finally, decrease intensity or absence of IGRA response and to a less extent of anti-spike serology were also correlated to reinfection which has occurred during the follow up. In conclusion, both IGRA and current anti-spike serology assays could be used at defined thresholds to monitor the vaccine response against SARS-CoV-2 and to simply identify non-responding individuals after a complete vaccination scheme. Two available specific tests (IGRA and anti-spike antibodies) could early assess the vaccine-induced immunity against SARS-CoV-2 at the individual scale, to potentially adapt the vaccination scheme in non-responder patients.

Monitoring of anti-drug antibodies in patients on ustekinumab is not routinely recommended in patients with inflammatory bowel disease (IBD) due to low rates of immunogenicity. Aim of study: The purpose of this study was to investigate the relationship between anti-drug antibodies detected by a drug-tolerant assay and loss of response (LOR) to therapy in a cohort of patients with IBD being treated with ustekinumab. Patients and Methods: This retrospective study consecutively enrolled all adult patients with moderate to severe active IBD who had at least 2 years of follow-up after ustekinumab was initiated. LOR was defined as CDAI > 220 or HBI > 4 for Crohn’s disease (CD) and partial Mayo subscore > 3 for ulcerative colitis (UC) and with a modification in disease management. Results: Ninety patients were included (78 CD and 12 UC; mean age 37 years). Median levels of anti-ustekinumab antibodies (ATU) were significantly higher in patients with LOR compared to those with ongoing clinical response (15.2 µg/mL-eq CI (7.9–21.5) and 4.7 µg/mL-eq CI (2.1–10.5), respectively; p = 0.04). The area under the ROC curve (AUROC) for ATU in predicting LOR was 0.76. The optimal cut-off point for identifying patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80% and specificity of 85%. Uni- and multivariate analyses showed that serum ATU ≥ 9.5 µg/mL-eq (hazard ratio (HR) 2.54, 95%CI (1.80–5.93)), p = 0.022, prior vedolizumab (HR 2.78, 95%CI (1.09–3.34), p = 0.019) and prior azathioprine (HR 0.54, 95%CI (0.20–0.76), p = 0.014) exposures were the only factors independently associated with LOR to UST. Conclusion: In our real-life cohort, ATU was identified as an independent predictor of LOR to ustekinumab in patients with IBD.

The human leukocyte antigen B27 (HLA-B27), associated with chronic inflammatory diseases is thus widely performed for diagnostic purposes. Genotyping by molecular biology is the current gold standard for HLA-B27 typing, but cheaper and faster flow cytometry methods have been developed.In this report, we compare analytical performances of three CE-IVD flow cytometry kits: IOTest™ and DuraClone B27™ from Beckman Coulter and BD HLA-B27™ from BD Biosciences on a Navios™ cytometer as compared to molecular biology.Routine analyses could conclude for HLA-B27 in197 patients (23.2%) and was not conclusive for 66 patients (7%, 8%). The experience revealed the needs to complete IOTest™ with a lineage marker (like CD3-APC) and a standardization procedure in detection of fluorescence. Comparative analysis considering 23/44 non-conclusive samples as negative, pointed out a 100% sensitivity and specificity of IOTest™ in determining genetically proved HLA-B27. Specificity of the BD HLA-B27The DuraClone B27™ specificity was poor using the manufacturer cutoff but raised to 100% with a 8.0 cutoff instead of 15.The three flow cytometry kits displayed satisfying performances but need adjustments. The DuraClone B27™ kit seems to be the best while the IOTest™ kit is not conclusive in 8% of cases. In most cases the use of molecular biology can be spared, but genotyping remains essential for patients whose HLA-B27 status cannot be determined with confidence by flow cytometry.

Background In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma—either ADA dose optimization or switching to vedolizumab or ustekinumab. Methods Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4.9 μg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. Results Adalimumab was optimized (n = 61 patients, 42 Crohn’s disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn’s disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P 24 months) than in the optimization group (13.3 months, P 500 μg/g (HR, 3.53; 95% CI, 1.16–10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13–0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. Conclusion In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

Multiple immunolabeling introduces high risks of interferences between fluorochromes. In an intend to analyze T cell clonality using CD3-APC Alexa750, CD4-Pac Blue, CD8-Krome Orange, CD56-PE-Cy7 and Vbeta clonotypes FITC and PE, we repeatedly observed a clear, unexpected signal on B770 (PE-Cy7) detector on the Vb subset mimicking a lymphoproliferative disorder. The aim of this study was to identify and prevent this source of artifact. The study was performed on a seven color panel performed on fresh whole blood, labeled, fixed, lyzed and analyzed on Navios Cytometer Beckman Coulter. Data were reanalyzed using Kaluza. Eleven tubes tested two clonotypes each with the same T cell backbone. Only one representative combination is presented. Using this panel, we observed repeatedly a strong CD56 PE-Cy7 (B755 LP) on all Vbeta1 T cell subsets but not on Vbeta 2-FITC T cells. The effect was still observed after removing CD56-PE-Cy7 (Full Minus One). Changing anti-CD3 APC-Alexa 750 with CD3APC, the B755 LP signal disappeared but a B695/30 signal appeared. Shifting to CD3-FITC abolished any unexpected red signal. This demonstrates a fluorescent energy transfer (FRET) between PE excited by the blue laser and Alexa750 to be excited by the red laser. Accordingly, the Vbeta PE fluorescence intensity was reduced when FRET happened and clearly increased when CD3-FITC was used instead. This observation clearly reminds that FRET can give misleading results in case of labeling of very close markers with complementary fluorochromes. This risk has to be considered in panel design.

Resume L’allergie par hypersensibilite immediate correspond a des manifestations aigues variees et peut poser des difficultes diagnostiques pour l’identification de l’allergene en cause et le suivi. En support de l’approche du clinicien, le biologiste propose des outils pour confirmer la nature de l’allergene et le caracteriser au niveau moleculaire par l’analyse des specificites reconnues par les IgE du patient. Cela permet de confirmer le diagnostic, d’evaluer les risques et les potentielles reactivites croisees. L’identification des composants peut aussi consolider la mise en place d’une immunotherapie et contribuer a son suivi. Dans le cas d’une reaction anaphylactique, la mesure des mediateurs liberes (tryptase et eventuellement histamine) confirme l’activation des mastocytes et/ou basophiles dont le facteur declenchant sera a determiner dans un second temps. Des kits de prelevement peuvent faciliter la procedure dans les situations d’urgence. En cas de doute diagnostique et d’un risque a l’exposition a l’allergene dans un test de provocation, le test d'exploration fonctionnelle pourra etre realise in vitro, en toute securite, sur les basophiles du patient. L’exploration biologique est un complement a l’analyse du clinicien et doit etre menee en partenariat de facon a ne pas semer le doute devant la detection d’ IgE qui ne traduit qu’une sensibilisation somme toute frequente, par rapport a l’allergie qui est une entite clinique potentiellement grave.

J’ai participe a l’automne dernier a une journee d’etudes organisee par une jeune equipe de l’ENS de Lyon qui portait sur le statut du corps dans les « Gender Studies » (ce sont les organisateurs qui avaient choisi la formule anglaise plutot que sa « traduction » francaise). M’ayant invitee en ma qualite de specialiste de ce champ, elles et ils m’ont pose diverses questions sur le sujet. Mais leur toute premiere question a porte sur la « diversite » – c’etait leur mot, sans doute un euphemism...

Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels).This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen RD, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen RD, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen RD), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody.Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen RD assay, respectively (P0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen RD assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen RD assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven RD), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen RD and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen RD drug-tolerant assay and in the same 2 patients by the 3 other assays.Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.

Anti-drug antibodies develop mostly during the induction therapy with anti-tumour necrosis factor (TNF) drugs and can be revealed by means of a drug-tolerant assay.To investigate whether the early detection of anti-drug antibodies during the induction therapy was predictive of treatment discontinuation.In a prospective study, consecutive patients with inflammatory bowel disease (IBD), who should start an anti-TNF, were enrolled and followed regularly during 24 months or less in case of non- or loss of response (LOR) or adverse events requiring treatment discontinuation. Anti-TNF levels and anti-drug antibodies were measured at week 2 for adalimumab (ADA) and weeks 2 and 6 for infliximab (IFX) using a drug-tolerant assay.One hundred and eight patients were enrolled (54 under ADA). At week 2, antibodies to ADA and to IFX were detected in 76% and 67% of patients. Time to treatment discontinuation was significantly shorter (P 0.001) in patients with antibodies to ADA ≥2.0 µg/mL-eq (6.0 vs 24 months, HR = 18.51, 95% CI [4.35-78.71]) or with antibodies to IFX ≥4.0 µg/mL-eq (5.5 vs24 months, HR = 13.89, 95% CI [4.08-47.31]) at week 2 compared to patients without positive antibodies. Antibodies to ADA and to IFX were predictive of treatment failure within 24 months with a sensitivity of 79% and 62%, and specificities and positive predictive values of 100%. In multivariate analysis, antibodies to ADA or to IFX at week 2 were the only factors associated with treatment discontinuation.The prevalence of antibodies to anti-TNF is high when detected early using a drug-tolerant assay, and their appearance predicts further treatment discontinuation.

The primary objective is to assess whether the POC assays to measure infliximab residual trough level in the serum of IBD patients were non-inferior to the ELISA techniques available on the market, and to determine which of them was the most robust. The second is to compare three different ELISA kits for monitoring anti-infliximab antibodies (ATI). The assays were carried out on patients’ sera using four ELISA kits from four different suppliers (three with a monoclonal antibody and one polyclonal) and two rapid techniques provided by BUHLMANN (Quantum Blue®) and R-Biopharm (Ridaquick) for monitoring infliximab levels. ATI were measured by three ELISA sets (Grifols, Theradiag, and R-Biopharm) which have different positivity limits and different units. We measured infliximab residual level and ATI in the serum of 90 IBD patients (85 treated with infliximab and five with adalimumab). All of the infliximab assays were very well correlated when analyzed with Spearman nonparametric correlation (0.93 ≤ r ≤ 0.99), and the two POC assays were also excellently correlated (r = 0.98). The ATI monitoring kits revealed a correlation ranging from 0.73 to 0.96 when comparing positive and negative patients. When normalizing the quantitative values between the different ELISA tests (expressed arbitrarily by using multiples of the positivity limits defined by each supplier), the Spearman r coefficient ranged from 0.81 to 0.93. The available evidence allows us to conclude that all of the infliximab monitoring assays correlate well and may be used for IFX monitoring; albeit variations in measured IFX concentration among different assays remain present, these assays could be interchangeable. The ATI monitoring techniques are all capable of detecting ATI-positive patients, but because of the difference in the positivity limits and the measurement units, it is better to follow a patient rate with one definite kit.

Introduction Basophils play a major physio-pathological role in hypersensitivity related diseases. Basophils express high affinity Immunoglobulin (Ig) E receptors (FceRI), IgG and complement regulatory. Basophils also have immunoregulatory activity through interaction with T cells. The aim of this study was to look for the expression of markers reflecting the activation status of peripheral Basophil in healthy donors. Method the study was performed on 29 healthy donors, 62% females with a mean age of 50.1 + 17.0 years. Basophils were identified on their expression of CD123 without HLA-DR and/or CD193 in two 8 colors panels including CD46, CD55, CD59, CD203c, CD32 (FcγRII), CD64 (FcγRIII), CD163, CD137L (4-1BBL), CD252 (OX40L), CD244 (2B4) and CD3 on whole blood. Basophil activation with anti IgE was performed on 14 donors. Results and discussion Our results confirmed the Basophil expression of CD123, CD193 and CD203 (the latter is strongly increased under stimulation). Complement regulatory proteins (CD46, CD55, CD59) were expressed at the same levels as on other leukocytes; CD46, CD59 expression being slightly increased under stimulation. CD32 and CD163 scavenger were slightly higher than on lympho and not influenced by activation. CD252 or CD137L were expressed at low levels and significantly induced by stimulation. Most of all, CD244 was highly expressed on Basophils as compared to any other leukocytes in fresh peripheral blood. Conclusions Our study shows that human resting Basophils express IgE and IgG Fc receptors and check point receptor CD244 that could potentially play a role in their previously reported immunoregulatory activity in sensitization and even in tumor immune escape.

From its founding, women’s and gender studies developed along a transatlantic epistemological and geopolitical axis. An interdisciplinary field, it fostered difficult conversations among disciplines that had each developed its own conceptual language. Women’s and gender studies is thus centrally concerned with crossing(s), whether crossing(s) functions as a political goal, a meta-metaphor for the field’s variegated theoretical endeavor, or as the name of a multifaceted epistemological problem. This essay focuses on the problem of translation as a form and act of crossing in the geopolitical context of globalization. It asks whether translation, a neohumanist practice of transnational exchange premised on the irreducibility of idioms and the hospitality to differences, can withstand the homogenizing pull of globalization. And it asks what the collapse of differences might do to an intellectual, political, and social field whose very raison d’être has been and continues to be the excavation of unrecognized or unwanted differences and the promotion of plurality.

The objective of the study was to evaluate whether Point-of-Care (POC) assays are equivalent to ELISAs for measuring residual trough levels of adalimumab (ADA) in a cohort of Inflammatory Bowel Disease (IBD) patients. ADA trough levels obtained by POC assays were used to optimize patients in daily clinical practice. Different assays (three ELISAs (Enzyme-Linked ImmunoSorbent Assay) from two different suppliers and two POC assays) were compared to measure ADA trough levels in a first cohort of 31 IBD patients. All assays revealed a high correlation within the assays, ranging from 0.86 to 0.99. Cut-off values were always higher with ELISAs than with POC assays. Then, a small prospective clinical study with a second cohort of 37 IBD patients was performed to compare POC assays and ELISAs for their ability to optimize patients on the basis of the measured ADA trough levels. The use of a POC assay to monitor ADA trough levels did not improve the follow-up of patients with loss of response, as they were always optimized whatever their ADA residual rate. For patients in clinical remission, a POC assay can be useful in some clinical situations to maintain or de-escalate ADA doses according to the measured trough levels. In conclusion, different assays for ADA monitoring are quite equivalent. A POC assay could be only useful for a proactive strategy for asymptomatic patients with a sub-therapeutic dose of ADA, but new therapeutic thresholds need to be identified.

Background Two scores have shown their interest in evaluating the luminal activity of CD in magnetic resonance (MR), the MARIA and Clermont scores, but their calculation can be complicated in clinical practice. Recently, the Spanish authors validated a new simplified MARIA score (MARIAs) and retrospectively showed a very good correlation with the initial MARIA score (1). The purpose of this study was to validate this correlation in an independent cohort and to compare its feasibility with other scores. Methods This was a retrospective analysis of all MR performed in our department to evaluate the luminal activity of CD. Two independent radiologists each calculated the MARIA, Clermont and MARIAs scores (wall thickness > 3mm, oedema, comb sign, ulcerations), each blind to the other and blind to clinical activity. In case of disagreement between the two radiologists, a third reader analyzed MR activity. Correlations were calculated between these three tests for the entire cohort. In addition, concordance tests were performed for predetermined thresholds of 7 to 11 for the MARIA score, 8.5 to 12.5 for the Clermont score and 1 to 2 for the MARIAs score. The duration of the analysis was reported for each reading. Isolated colonic CD were excluded from the study. Results One hundred and twenty-one CD were included (65 in clinical and biological activity, 33% ileal phenotype, mean age: 38.5 years, sex ratio M/F = 54.5%). The agreement between the MARIA score between 7 and 11, the Clermont score between 8.5 and 12.5 and the MARIAs score between 1 and 2 was 0.92 (Fleiss kappa test). The correlation between the MARIA score and its simplified score was very strong (r = 0.93; 95% CI: 0.9–0.95) as well as between the Clermont score and the MARIAs score (r = 0.92 95% CI: 0.89–0.95). Inter-observer agreement was significantly higher in the calculation of the MARIAs score (96%) compared with 80% for the MARIA and Clermont scores (p = 0.04). Reading time was significantly faster for the MARIAs score (3.45 ± 0.4 min) compared with the MARIA (10.05 ± 1.2 min) and Clermont (13.5 ± −3.5 min) scores (p < 0.01). Positive predictive values for deep remission (clinical remission and calprotectin < 250 µg/g stool) were 95% at thresholds Conclusion In this independent cohort, we confirm the very strong correlation between the simplified MARIA score and the two reference scores (MARIA and Clermont) in the analysis of MC luminal activity as well as its rapid calculation and strong inter-observer agreement.

Background SB2, an infliximab (IFX) biosimilar to the reference infliximab (R.I.) product (Remicade), received approval in the European Union for all IFX indications. Many decision algorithms based on the measurement of IFX trough levels and antibodies to infliximab are being increasingly used to optimize IFX treatment. The aim of our study was to evaluate whether the biosimilar SB2 could be efficiently monitored using the LISA-TRACKER IFX and anti-IFX assays developed by Theradiag (Croissy Beaubourg, France). Methods Standard curves of R.I. and SB2 were compared, and then accuracy of the LISA-TRACKER IFX assay in detecting the spiked concentration of SB2 was measured. Levels of IFX from SB2 spiked samples and R.I. clinical samples were calculated. Intra-run and inter-run imprecision were also measured with SB2 spiked samples. The ability of polyclonal antibodies directed against R.I. to block the detection of SB2 using the LISA-TRACKER IFX assay and the capacity of SB2 to block the detection of anti-R.I. antibodies using the LISA-TRACKER anti-IFX assay were tested. Results Twelve patients treated with SB2 including 2 patients with SB2-specific antibodies were measured with the LISA-TRACKER anti-IFX assay. We demonstrated that the LISA-TRACKER assay is suitable for the quantification of SB2 in human serum samples. The percentage of recovery was between 82% and 113%. High intra-run and inter-run imprecisions were obtained with the LISA-TRACKER infliximab assay for the quantification of SB2 (SD ranged from 3.3% to 17.9%). The SB2-blocking capacity of R.I. polyclonal antibodies in spiked samples was demonstrated with inhibition between 80% and 97%. SB2 trough levels and anti-SB2 antibodies have also been confirmed in SB2-treated patients. Conclusions LISA-TRACKER IFX and anti-IFX assays are suitable for the monitoring of patients treated with SB2.

International audience; Background: Vedolizumab (VDZ), a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease (IBD) who have not adequately responded to standard therapies, and high levels of vedolizumab trough levels (VTL) have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is up-regulated by retinoic acid (RA). Aim: To determine the relations between soluble MAdCAM-1 (sMAdCAM-1) and RA concentrations with clinical remission during VDZ maintenance therapy. Methods: In a retrospective study performed in IBD patients treated with VDZ we measured VTL, sMAdCAM-1 and RA concentrations. Results: Among the 62 included patients (38 Crohn's disease) 24 relapsed and 38 stayed in remission between weeks 10 to 30 after VDZ initiation. During this maintenance therapy, median values of VTL and RA were 15.4 \textmug/mL and 0.97 ng/mL, whereas sMAdCAM-1 was undetectable (\textless 0.41 ng/mL) in 67.3% of samples. The positive predictive value (PPV) of undetectable sMAdCAM-1 for clinical remission was 80.0% with a corresponding sensitivity of 74.6%. On multivariate analysis undetectable sMAdCAM-1 and high VTL (\textgreater 19 \textmug/mL) were independently associated with clinical remission (OR=7.5, p=0.006 and OR=2.2, p=0.045, respectively). The combination of sMAdCAM-1 \textless 0.41 ng/mL and VTL \textgreater 19 \textmug/mL was the best pharmacokinetic profile with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher (p=0.0001) before VDZ therapy than during the follow-up (sMAdCAM-1: 40.5 vs \textless 0.41 ng/mL; RA: 1.7 vs 0.97 ng/mL). Only RA \textgreater 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (AUROC=80.7%). Conclusions: Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies.

Background Nearly 40% of patients who failed on ADA have therapeutic residual trough levels (pharmacodynamic failure). It is then recommended to change the therapeutic class to a non-anti-TNF biological. In this situation, however, a quarter of patients respond to an ADA dose optimisation. The purpose of this work was to compare these two strategies and identify predictors of response for each strategy. Methods This is a bi-centre, retrospective study based on a clinical and biological database that included patients followed from 2015 to 2016 with an IBD in maintenance treatment with ADA as monotherapy (40 mg/sc/14 days) and in loss of response (CDAI > 220 with faecal calprotectin > 250 µg/g stool for CD and Mayo score > 6 with endoscopic sub-score > 1 for UC). All patients included had residual trough ADA levels > 5 µg/ml. Relapsed patients were treated either with dose optimisation (ADA: 40 mg/sc/7 days) or other biotherapy (ustekinumab or vedolizumab, according to classic regimens and dosages). The primary endpoint was the relapse-free survival rate (defined as clinical and biological or endoscopic activity requiring therapeutic change). The survival curve analysis was performed using the Kaplan–Meier method and the log-rank test. Results In total, 125 patients (mean age: 38 years, 75% CD, sex ratio M/F = 57%, previous infliximab = 42%) were included and 50 were treated with another biological (Vedolizumab: 30 patients, Ustekinumab: 20 patients). The characteristics of the two groups were comparable except for significantly higher levels of CRP and faecal calprotectin at inclusion in the biological change arm. The duration without relapse was significantly longer after the class change (p = 0.0005; HR = 0.39[0.23–0.68]). The relapse-free survival rates at 54 weeks were 35% for the optimised arm and 66% for a class change (p = 0.04). In multivariate analysis, the only long-term response predictor was biotherapy class change vs. ADA dose optimisation (p = 0.042; HR = 0.3[0.02–0.95]). Previous use of IFX or type of IBD were not associated with relapse. For the dose optimisation strategy, in multivariate analysis, only age < 40 years was associated with a progression without relapse (p = 0.007; HR = 0.09[0.01–0.52]). Residual ADA levels were not predictive of response to optimisation (p = 0.73) and no ADA quartile was significantly associated with a more favourable clinical response. For the class change strategy, no relapse predictors were isolated in univariate analysis. Conclusion In patients on ADA who are losing response despite therapeutic rates, the change of class to non-anti-TNF biotherapy allows a significantly greater lasting response than a dose optimisation strategy for ADA.

Background Several studies have shown a link between circulating anti-TNF levels during induction and clinical progression during IBD. There are less data on the detection of anti-drug antibodies at induction because it requires the use of so-called ‘drug-tolerant’ techniques. The purpose of our study was to investigate in two distinct cohorts (IBD patients on IFX or ADA) whether the early appearance of anti-drug antibodies measured using a drug-tolerant test was associated with clinical progression. Methods In a retrospective study, we included all patients followed in our department for at least 3 months and having had an anti-TNF dosage from W2 of induction under ADA or IFX. At follow-up, therapeutic failure was defined by the obligation to optimise, a change in biotherapy, the use of corticosteroids or surgery. IFX and ADA levels were measured routinely (Lisa-Tracker; Theradiag) and anti-medicine antibodies were detected by ‘drug-sensitive’ ELISA technique (Lisa-Tracker; Theradiag) or ‘drug-tolerant’ as previously described [1]. Patients with a positive rheumatoid factor were excluded. Results 54 patients were included in ADA (mean age: 36 years, sex ratio M/F = 54%, CD: 65%, combotherapy: 10%) and 54 treated with IFX (mean age: 35 years, sex ratio M/F: 46%, CD: 62%, combotherapy: 65%). The search for anti-drug antibodies to W2 using a ‘drug-sensitive’ technique did not reveal any antibodies, whereas 74% of patients on ADA (AAA > or = 2.5 µg/ml eq) and 55% of patients on IFX (ATI > or = 4µg/ml eq). Under ADA, the duration of treatment until loss of response was significantly shorter in the presence of AAA at W2: 6 months vs. 24 months (HR = 18.51; 95CI = 4.35–78.11; p < 0.001). In multivariate analysis, the only independent factor associated with failure was the rate of ADA antibodies to W2 (HR = 18.17; 95CI: 4.27–77.45; p < 0.001). Under IFX, the treatment time to loss of response was significantly shorter in the presence of ATI to W2 (ATI > or = 4µg/ml eq): 5.5 months vs. >24 months (HR = 13.89; 95CI = 4.08–47.31; p < 0.001). In multivariate analysis, the only independent factor associated with failure was the level of anti-IFX antibodies to W2 (> or = 4 µg/ml eq) (HR = 8.07; 95CI: 3.13–20.82; p < 0.001). The higher quartiles of ATI and AAA were significantly associated with poor outcomes (p < 0.001 for each anti-TNF). Conclusion The early onset of anti-drug antibodies in the induction phase as early as W2 is the only isolated independent factor associated with loss of response. Anti-drug antibody frequencies are very high when measured with a drug-tolerant test and these Abs may be more neutralising with ADA than with IFX.

Background In a recent prospective, randomised trial, we showed that the rates of clinical failure and occurrence of unfavourable pharmacokinetics using a drug-sensitive assay after a switch of anti-TNF were significantly higher in monotherapy compared with combination therapy (Log-rank test p < 0.0001), whatever the anti-TNF used in IBD patients. We aimed in a post hoc analysis to assess the time-course of antidrug antibodies in the two groups of patients using a drug-tolerant assay previously described (1). Methods After switching of anti-TNF under mono or combotherapy, blood samples were uptake at various time-points (6, 12, 18 and 24 months). Using a drug-tolerant assay, we defined pharmacokinetic failure when antidrug antibodies were detected (> 2.5 μg/ml Eq). Transient anti-drug antibodies were defined as antibodies that appeared during the course of anti-TNF therapy with no clinical worsening, and finally that disappeared after 2 consecutive measurements. Results Ninety patients were analysed. According to a drug-tolerant assay, the occurrence of antibodies against anti-TNF was significantly higher in patients under monotherapy (log-rank test p < 0.0001 (HR = 3.36 [1.94–5.86]) than under combination therapy. The rates of anti-drug antibody were significantly lower under IFX-AZA combotherapy compared with ADA-AZA combotherapy or under monotherapy. Monotherapy ADA (HR = 5.55[2.46–12.34]) or IFX (HR = 6.05[2.67–13.70]) and combination therapy ADA-AZA (HR = 3.34 [1.407.98]) increased significantly the rates of pharmacokinetic failure using a drug-tolerant assay compared with IFX-AZA combotherapy. The time-course without pharmacokinetic failure was significantly different between the 4 groups of patients from 15 months (p = 0.04) but was not significantly different at 6 months (p = 0.12). Overall, 9% of patients developed transient antibodies. Detection of antibodies against anti-TNF at 6 months using a drug-tolerant assay predicted significantly an immunogenic failure assessed previously by a drug-sensitive assay with a sensitivity of 57.1%, a specificity of 92.7%, a positive predictive value of 90.3%. In contrary to the association between clinical failure and immunogenic failure using drug-sensitive assay, the association of detectable drug and positive antibodies using a drug-tolerant assay was not significantly associated with clinical failure (HR = 1.3[0.3–6.8], p = 0.51). Conclusion Pharmacokinetic failure using a drug-tolerant assay was significantly lower under combotherapy, especially for IFX-AZA. Detection of anti-drug antibodies could predict pharmacokinetic failure. Reference

anne-emmanuelle berger is Professor of French Literature at Cornell University and Visiting Professor at the Centre de Recherches en Etudes Féminines at Paris VIII University. Her recent publications include Algeria in Others' Languages (Cornell University Press, 2002)and Scènes d'aumône: Misère et poésie au XIXe siècle (Champion, 2004). She is currently writing on Derrida.

How and why do some contemporary body practices that take place at the crossroads of aesthetics and politics give to the critics of the sexual order a dimension that is both experiential and experimental? How do they produce meaning and effects that are susceptible of questioning the dominant rational order? These are the questions that guide the present research work. To answer them, I focus on a specific practice that operates as a tool to the feminist struggle: the drag king workshops. I propose here to analyze them at the light of a decentered reading of Antonin Artaud’s theater of cruelty. This reading relates the artaudian notion of cruelty to the notions of performance and performativity to highlight the creative and potentially subversive dimension of a corporal and collective practice. By relating aesthetic transformation and political engagement, this work on a “political travestying practice” explores the critical dimension of a kind of questioning our own corporal positions reflecting the scale of privileges and oppressions constituted by the dominant régime of rationality.My approach to these questions is also a situated approach, hence the autobiographic dimension of the process I propose here. Artaud has been a harsh critic of the logical and aesthetical forms of “western” rationality. That is why his reading can be useful to think the western closure. In fact, from my own position as a sudaka, a Colombian migrant, taken within a complex colonial history, I articulate, through my reading of Artaud’s thought and itinerary the critic of the sexual order and the critic of a dominant rationality. Faithful to a conception of the consubstantial connections between aesthetics and politics, as well as between practice and theory, I put on stage my encounter with Artaud and his own encounter with Mexico, a double encounter that informs my reading and my experience in the drag king workshops.; Comment et pourquoi certaines pratiques contemporaines du corps, qui se déroulent au carrefour de l’esthétique et du politique, donnent-elles à la critique de l’ordre sexuel une dimension à la fois vécue et expérimentale ? Comment produisent-elles un sens et des effets susceptibles de mettre en question l’ordre rationnel dominant ? Telles sont les questions qui guident ce travail de recherche. Pour y répondre, je me centre sur une pratique spécifique qui sert d’outil de lutte féministe : les ateliers drag king. Je propose de les analyser à la lumière d’une lecture décentrée du théâtre de la cruauté d’Antonin Artaud : il s’agit d’une lecture qui relie la notion artaudienne de cruauté à celles de performance et de performativité, afin de souligner la dimension créative et potentiellement subversive d’une pratique corporelle et collective. Ce travail sur un « travestissement politique » explore la dimension critique d’un certain questionnement de nos positions corporelles, là où celles-ci reflètent l’échelle des privilèges et des oppressions constituées par le régime de rationalité dominant.Mon approche de ces questions est une approche située, d’où la dimension autobiographique du parcours que je propose. Artaud a été un grand pourfendeur des formes logiques et esthétiques de la rationalité « occidentale ». C’est pourquoi il me semble que son expérience peut être utile pour penser la clôture occidentale. En effet, sa pensée et son itinéraire me permettent d’articuler ensemble critique de l’ordre du sexe et critique de la rationalité dominante, à partir de ma position de migrante sudaka, prise dans une histoire coloniale complexe. Fidèle à une conception du rapport consubstantiel entre esthétique et politique comme entre pratique et théorie, je mets en scène ma rencontre d’Artaud et sa propre rencontre avec le Mexique : double rencontre qui informe ma lecture et mon expérience des ateliers drag kings.

"Danse et genre : épistémologie d'un espace de recherche" constitue un mémoire de synthèse qui vise à tracer les contours d'un champ de recherches articulant études de genre et études en danse. L'objectif est de dégager un certain nombre d'éléments spécifiant cet espace encore peu développé en France, de poser des bases, ou du moins des jalons, afin de le baliser et de dégager des perspectives à poursuivre, également de faire une double généalogie des démarches et des études ayant abouti à sa constitution. Au-delà de ces objectifs, il y a l'enjeu d'en démontrer l'importance scientifique, notamment aux actrices et acteurs des deux pôles, et de sortir d'une méconnaissance réciproque. Le mémoire comporte quatre chapitres. 1. "Introduction et cadres généraux" présente le concept de genre et la position théorique où je me situe, l' "objet" danse – en se gardant bien de le définir – et quelques aspects spécifiques des études en danse, avant de tenter de cerner un champ méthodologique défini, non pas a priori, mais construit de façon pragmatique au fil du parcours et focalisé sur une pratique de l'inter et de la trans -disciplinarité, justifiée par la double complexité des objets et des problématiques posées, mais résultant aussi d'un choix et d'une expérience personnelle de la recherche. 2. Partout et depuis presque toujours, la danse est une activité et un art marqués par le genre, au point qu'il n'est guère possible de l'étudier d'un point de vue historique ou anthropologique sans introduire cette dimension qui structure ses pratiques. Le deuxième chapitre, "Danse et genre, croisements féconds", présente trois perspectives pour envisager les liens entre danse et genre. La première et la plus fondamentale a trait à la façon dont le genre travaille les matières de la danse et dont, réciproquement, ces matières travaillent le genre, que ce soit pour participer à sa stabilité et à sa légitimité ou, à l'inverse, en perturbant ses processus et en s'y opposant. La deuxième perspective, sous un angle plus sociologique, présente quelques effets du genre dans le secteur chorégraphique en France, à l'heure actuelle. Enfin, découlant de ce qui précède, la troisième évoque les croisements possibles, souhaitables, entre recherches en danse et recherches en genre.3. Le chapitre "Questionnements croisés dans les pratiques et les savoirs - Contextes anglo-saxon et français" permet d'esquisser une généalogie de l'espace constitué, en s'intéressant à la façon dont les questions féministes et de genre ont pénétré le champ des pratiques et celui des recherches en danse, et réciproquement à celle dont la danse a – ou n'a pas – investi le champ des pratiques comme des recherches féministes. Une telle étude ne peut manquer de s'intéresser aux différences culturelles entre la France et les pays anglo-saxons.4. Enfin, "La catégorisation féminine de la danse, paradigme du genre", est un chapitre consacré à une question fondamentale et préalable à toute autre recherche, celle de la représentation symbolique de la danse comme féminine, représentation qui biaise une grande partie des approches et pèse lourdement, tant sur le secteur des pratiques chorégraphiques que sur la recherche. Il s'agit de s'interroger sur les sources de cette catégorisation analysée comme paradigmatique des mécanismes de catégorisation de genre, induite par des processus de hiérarchisation, d'exclusion et de constitution d'une altérité au modèle masculin.

"Histoire et esthétique de la danse de ballet au XIXe siècle - Quelques aspects au prisme du genre, féminisation du ballet et stigmatisation des danseurs" est une synthèse de travaux sur la danse de ballet au XIXe siècle, à partir d'une problématique initiale concernant la fixation de la féminisation - à la fois symbolique et des pratiques - de la danse. Quatre chapitres et un divertissement composent ce mémoire. Le premier chapitre porte sur la question des sources et des spécificités des matériaux dont disposent les chercheuses et chercheurs en danse, sur les récits historiques qui souvent, loin de pouvoir constituer la base de recherches actuelles, se révèlent être des pièges, confondant représentations sociales et faits historiques ; ce phénomène relève essentiellement de biais liés au genre/gender.Le deuxième présente les éléments factuels nécessaires à la compréhension de l'émergence et des évolutions du ballet-pantomime romantique, son cadre institutionnel et ses publics, les principales œuvres qui font repères. Un troisième chapitre interroge les spécificités du ballet-pantomime, pour comprendre sa place dans l'histoire de la danse et du Romantisme. Il aborde les enjeux esthétiques auxquels la danse a été confrontée au XIXe siècle, la façon dont elle a évolué dans un réseau de redéfinitions des arts et des artistes, pour tendre vers une autonomie simultanément artistique et comme champ social. Les nouvelles valeurs et redéfinitions s'articulent de plusieurs façons à des problématiques de genre ; elles orientent à différents niveaux la féminisation du ballet et la stigmatisation des danseurs.Le chapitre suivant, "l'esprit du temps : la féminisation symbolique et professionnelle du ballet", traite la question initiale et centrale des dynamiques et des modalités avec lesquelles le contexte a provoqué, en quelques années, un changement profond dans les représentations sociales de la danse de ballet, essentialisée en art féminin où un homme n'était plus légitime. Pour clore ces recherches, en guise de "divertissement", figure une recherche sur le ballet La Révolte au sérail ou La Révolte des femmes, de 1833, seul ballet-pantomime romantique à faire référence à des évènements politiques de son temps et à mettre en scène des revendications féministes.

My dissertation explores the ways feminists mobilize the notion of "the universal" in their claims for justice. Since the late 1950s, the use of universalism in feminist discourse, whether claimed or latent, has been highly criticized. Namely, this critique highlights the ethnocentric, imperialist, and patriarchal philosophical framework underlying this discourse that was inherited from Enlightenment theory. In recent years, queer and postcolonial feminisms have expanded on this critique, urging feminists to explore ethical and contextual approaches while distancing themselves from the rhetoric of (universal) human rights. I argue in this dissertation that, despite the importance of these various critiques, we must retain "the universal" as a horizon for feminist theories of justice. Beginning with the hypothesis that "the universal" is always ambiguous, or equivocal, I argue that nonetheless it can still play an important role, at both the political and intersubjective levels. To think of "the universal" as an ambiguous concept enables us to reconceive the subject itself, as well as a postmodern ethics in light of queer and postcolonial critiques. After examining both feminist critiques that were addressed to some theories of justice (in particular Rawls') and feminist ethical debates (including ethics of care or ecofeminist ethics), I suggest the possibility of articulating a feminist ethic with a theory of fair or just institutions. My claim is that, while maintaining the ambiguity of "the universal," such a conception of justice helps us not only to conceive new forms of transnational solidarities, but also to rethink the terms of a feminist cosmopolitanism., Ce travail explore la façon dont les féministes mobilisent la notion d'universel dans leurs revendications de justice. Depuis les années 1950, l'universalisme latent ou assumé de certains discours féministes a été beaucoup critiqué. On a reproché à ces discours de se déployer dans les cadres philosophiques à la fois ethnocentriques, impérialistes et patriarcaux hérités des Lumières. Ces critiques, qui sont principalement relayées, depuis quelques années, par les féminismes queer et postcoloniaux, ont conduit certaines féministes à prendre leurs distances avec la rhétorique des droits universels, et à privilégier des approches éthiques et contextualistes. Tout en parcourant la diversité de ces critiques, ma thèse examine la possibilité de maintenir l'universel à l'horizon d'une théorie féministe de la justice. Partant de l'intuition selon laquelle l'universel est d'emblée ambigu, ou équivoque, je suggère qu'il est possible de le conserver comme un horizon des luttes féministes, au niveau intersubjectif comme au niveau politique. Concevoir l'universel comme ambigu offre selon moi la possibilité de repenser le sujet et les éthiques postmodernes à la lumière des critiques adressées par les féministes queer et postcoloniales. Après avoir examiné les critiques féministes adressées à certaines théories de la justice (principalement celle de Rawls), mais également les débats féministes en matière d'éthique (éthiques du care, ou éthiques écoféministes par exemple), je propose d'articuler une éthique féministe à une théorie politique des institutions justes. Tout en maintenant l'ambigüité de l'universel, cette conception de la justice permet non seulement de concevoir de nouvelles formes de solidarités transnationales mais aussi de repenser les termes d'un cosmopolitisme féministe.