AA Amyloidosis in the Course of HIV Infection: A Report of 19 Cases Including 4 New French Cases and a Comprehensive Review of Literature

International audienceIntroduction: HIV infection has been recently retained as an unclear cause of AA amyloidosis. Our aim was to investigate cases of AA amyloidosis associated with HIV infection to understand if it could be considered as a cause of AA amyloidosis.Methods: A comprehensive literature review was conducted as well as retrospective study from French cases collected from our national reference center for AA amyloidosis.Results: Altogether, 19 patients with AA amyloidosis and HIV infection were found with 68% of men and median age at amyloidosis diagnosis of 38 years (range 28-75 years). Clinical presentation was nephrotic syndrome in 94% (n = 17/18). Among patients with renal involvement and assessable outcome (n = 17), 11 (64.7%) progressed to chronic kidney disease, with 6 (35%) end-stage renal disease. Seventy-five percent of patients had uncontrolled HIV infection and 71.4% CD4 counts <400/mm3 at amyloidosis diagnosis. Repeated or chronic bacterial or fungal infection was found in 47% of cases and a history of parenteral drug use in 55% of patients. Three patients had no classical or at least no suspected AA amyloidosis cause found or reported.Conclusions: AA Amyloidosis is a rare condition in HIV patients with common renal involvement and significant risk of progression to chronic renal insufficiency. Because of the frequency related to other inflammatory conditions in this population, HIV is probably not an independent risk factor for AA amyloidosis

Anti-PM-Scl antibodies–positive patients encompass three different groups with distinct prognoses

International audienceAbstract Objective To help identify homogeneous subgroups among patients with anti-PM-scleroderma-antibodies (PM-Scl-Abs) positive auto-immune diseases regardless of diagnostic classifications. Material and methods This multicentric (four hospitals) retrospective study collected all consecutive patients (from 2011 to 2021) with positive testing for anti-PM-Scl-Abs in a context of CTD. Subgroups of patients with similar clinico-biological phenotypes were defined using unsupervised multiple correspondence analysis and hierarchical clustering analysis of the features recorded in the first year of follow-up. Results One hundred and forty-two patients with anti-PM-Scl-Abs were evaluated and 129 patients were included in the clustering analysis and divided into three clusters. Cluster 1 (n = 47) included patients with frequent skin thickening, digestive involvement and interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP). They were more likely to develop progressive fibrosing ILD. Cluster 2 (n = 36) included patients who all featured NSIP with frequent organizing pneumonia–associated pattern and mechanic’s hands. This subgroup had increased risk of relapse and ILD was characterized by a good functional outcome. Cluster 3 (n = 46) was characterized by predominant or isolated musculoskeletal involvement and frequently matched UCTD criteria. Although very frequent among anti-PM-Scl-Abs positive patients, muscle involvement was less discriminating compared with skin thickening and ILD pattern to classify patients into subgroups. Conclusion Anti-PM-Scl-Abs associated auto-immune diseases are segregated into three subgroups with distinct clinical phenotype and outcomes. Skin thickening and NSIP are determinant predictors in segregation of theses populations

Cutaneous vasculitis occurring in the setting of systemic lupus erythematosus: a multicenter cohort study.

OBJECTIVES To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with systemic lupus erythematosus (SLE), focusing on diagnosis classification and impact on overall SLE activity. METHODS Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by 1) data from pathology departments of three university hospitals and 2) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index. RESULTS Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n = 21; 54%) and urticarial lesions (n = 18; 46%); lower limbs were the most common location (n = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren's syndrome (51%) was found compared with SLE patients without CV from the French referral center group (12%, p < 0.0001) and the Swiss SLE Cohort (11%, p < 0.0001). CV were mostly classified as urticarial vasculitis (n = 14, 36%) and cryoglobulinemia (n = 13, 33%). Only 2 (5%) patients had no other cause than SLE to explain the CV. Sixty-one percent of patients had inactive SLE. CONCLUSION SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE

La rencontre

Le cinéma est, de bien des façons et à bien des titres, un art de la rencontre. Dans la filiation des frères Lumière, filmer, c’est aller, tout simplement, à la rencontre du réel, du plus lointain au plus familier ; dans cette aventure, le familier devient étrange, l’étranger devient proche : c’est sur ce paradoxe que sont fondés le cinéma ethnographique et le documentaire. Dans la voie Méliès, le cinéma est une rencontre avec l’imprévu, l’improbable ou l’impossible ; tout le cinéma fantastique, en un sens, découle de ce désir de rencontre avec ce qui relève toujours de l’impensable. Plus quotidiennement encore, le cinéma, où les aléas de l’enregistrement des images jouent un si grand rôle, est l’art des hasards heureux ; combien de cinéastes n’ont-ils pas dit leur amour de l’improvisation, de l’accident, et combien n’ont-ils pas poussé leurs acteurs (voire leurs techniciens) à les surprendre ? Rencontres, à bien des niveaux, qui se traduisent aussi dans l’énorme proportion des fictions qui mettent en jeu ce thème – la rencontre amoureuse, bien sûr (« boy meets girl »), mais aussi la rencontre de l’autre, la rencontre du danger et de l’aventure, la rencontre de l’inconnu, la rencontre du sublime, ou tout simplement, la rencontre de soi-même

BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus

International audienceObjectives Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination.Methods In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose.Results BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (β=−78, p=0.007; β=−122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (β=2, p=0.018; β=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.Conclusion MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up

‘When you have your back to the wall, everything becomes easy’: performance and direction in the films of Catherine Breillat

French director Catherine Breillat has gained notoriety for her distinctly personal portrayal of gender relations and intimacy. With the inclusion of sexually explicit scenes, such as those featuring loss of virginity and/or rape, her films explore subjects of emotional, as well as visual, taboo. In this article the author examines Breillat’s preproduction and on-set practices, particularly focusing on her control of actors’ bodies. Breillat’s risk-taking seems to involve a lack of contact with actors in the preproduction stage of each film, meaning that the camera is rolling when scenes play out for the first time. The director counters this risk with long periods of casting and her technique of control on-set: the precise choreography of each shot. Rather than allow actors to move and act on the emotional responses they draw from the script, Breillat physically puts them into position, choreographs their movement in advance and models the performance she wishes to capture. The author suggests that, by taking risks as director, notably by pushing cast and crew into fearful and uncomfortable situations, Breillat is able to capture moments of onscreen intimacy in a subversive manner. The author draws upon her own interview with Breillat (undertaken during a period of screen testing for her latest film, Abus de faiblesse [2013]), as well as a range of other primary and secondary sources, to provide a new reading of key scenes in films such as Romance (1999) and À ma sœur (2001)

Lower disease activity but higher risk of severe COVID-19 and herpes zoster in systemiclupus erythematosus patients with pre-existing autoantibodies neutralising IFN-

International audienceObjectives: Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are alsooverproduced in patients with systemic lupus erythematosus (SLE). Auto-antibodies (AAbs)neutralising IFN-, - and/or - subtypes are strong determinants of hypoxemic COVID-19pneumonia, but their impact on inflammation remains unknown.Methods: We retrospectively analysed a monocentric longitudinal cohort of 609 patients withSLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed byabolishment of Madin-Darby bovine kidney cells protection by IFN-α2 against vesicularstomatitis virus challenge. Serum neutralising activity against IFN-, - and - was alsodetermined with a reporter luciferase activity. SARS-CoV-2 antibody responses were measuredagainst wild-type spike antigen, while serum-neutralising activity was assessed against theSARS-CoV-2 historical strain and variants of concerns.Results: Neutralising and non-neutralising anti-IFN- antibodies are present at a frequency of3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-, unlike nonneutralisingAAbs, are associated with reduced IFN- serum levels and a reduced likelihood todevelop active disease. However, they predispose patients to an increased risk of herpes zosterand severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE ismostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-AAbsdo not interfere with COVID-19 vaccine humoral immunogenicity.Conclusion: The production of non-neutralising and neutralising anti-IFN-I antibodies in SLEis likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficialeffect on disease activity, yet a greater viral risk. This finding reinforces the recommendationsfor vaccination against SARS-CoV-2 in SLE

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

International audienceCoronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches

VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation

Abstract Acquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1β and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome