Incidence et caractéristiques des hémopathies malignes au cours de l’artérite à cellules géantes
Introduction L’arterite a cellules geantes (ACG) est une vascularite du sujet âge au cours de laquelle les cellules mononucleees jouent un role physiopathologique majeur. L’hematopoiese clonale est un phenomene dont la frequence augmente egalement avec l’âge et qui conduit a l’apparition de mutations responsables de la survenue d’hemopathies malignes (HM) ou de mutations des cellules effectrices de l’immunite responsables de pathologies inflammatoires. Notre hypothese est qu’il existe une association specifique entre certaines HM et l’ACG. Nous avons pu etudier cette hypothese en croisant les donnees du registre des hemopathies de Cote d’Or (RHEMCO) et celles de tous les laboratoires d’anat…
Interstitial Lung Disease during ANCA-Associated Vasculitis: A Poor-Prognosis Factor
IF 7.873; International audience
Le tocilizumab corrige le déséquilibre de la balance Th17/Treg chez les patients atteints de polyarthrite rhumatoïde
Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
OBJECTIVE: From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. METHODS: Patients with active RA for whom TCZ had been prescribed by a rheumatologist were en…
Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.
Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia.This retrospective observational study included all adult patients with a gammaglobulin level6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin6.4 and ≥5g/L, mild hypogammaglobulinemia).Among the 4011 serum electrophoreses, 570 samples from 389 patients …
Modification de la réponse immunitaire au cours de la maladie de Rendu-Osler
Introduction La maladie de Rendu-Osler (MRO) est une maladie genetique vasculaire rare caracterisee par une neo-angiogenese deregulee aboutissant a des epistaxis anemiantes parfois associees a malformations arterio-veineuses (MAV) pulmonaires, hepatiques ou cerebrales. La MRO est egalement associee a une lymphopenie T predominant sur les CD4+ dont les causes et les consequences sont mal connues. L’objectif de ce travail est de decrire les polarisations lymphocytaires Th1, Th2, Th17, Th1-17 et Treg au cours de la MRO. Patients et methodes Les patients atteints de MRO confirmee genetiquement ont ete prospectivement inclus lors de leur suivi habituel. Le score de severite des epistaxis (ESS), …
« Fausses et autres » artérites temporales
Resume L’arterite a cellules geantes (ACG) est la plus frequente des vascularites affectant l’artere temporale (AT). Neanmoins, d’autres types de pathologies vasculaires, qu’il s’agisse de vascularite ou non, peuvent toucher l’AT. Parmi les vascularites, on peut citer les vascularites necrosantes, en particulier les vascularites associees aux anticorps anti-cytoplasme des polynucleaires neutrophiles (ANCA) qui peuvent affecter les petits vaisseaux peri-adventitiels de la paroi de l’AT et mimer certains symptomes de l’ACG, ces derniers n’etant generalement pas isoles, ce qui doit faire rechercher les ANCA. Certaines vascularites infectieuses peuvent egalement toucher l’AT comme l’infection p…
Haemolytic-uraemic syndrome during severe lupus nephritis: efficacy of plasma exchange
Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic-uraemic syndrome (HUS) is less frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.
Reducing the initial number of rituximab maintenance-therapy infusions for ANCA-associated vasculitides: randomized-trial post-hoc analysis
AbstractObjectiveThe randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter’s titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12.MethodsMAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free surviv…
Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fc&gamma
Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).
Abstract Purpose Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. Methods Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d’etude francais des arterites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was…
ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance
Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its con…
Infarctus du myocarde au cours de l’artérite à cellules géantes : étude de cohorte
Introduction Le risque d’evenement cardiovasculaire est accru au cours de l’arterite a cellules geantes (ACG), en particulier dans les premiers mois suivant le diagnostic de la vascularite [1] . L’objectif de ce travail etait de decrire les caracteristiques des infarctus du myocarde (IDM) survenant chez des patients atteints d’ACG et de les comparer avec des IDM survenant chez des patients ne presentant pas d’ACG au moment de leur IDM. Patients et methodes Les patients atteints d’ACG ont ete identifies parmi la liste des biopsies d’artere temporale (BAT) qui montraient des lesions d’ACG et qui avaient ete analysees entre le 1er janvier 2001 et le 31 decembre 2016 dans les deux laboratoires …
L’augmentation de la réponse Th17 au cours de la maladie de Horton et de la PPR est liée à des modifications fonctionnelles et non quantitatives de leurs précurseurs : les lymphocytes T CD4+ CD161+
Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia
IF 7.607; International audience; Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constit…
Physiopathologie des vascularites primitives des gros vaisseaux
Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. T…
Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.
International audience; OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients wi…
Stroke associated with giant cell arteritis: a population-based study
Background Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. Methods All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptom…
Tocilizumab en association à la prednisone au cours des 3 premiers mois de traitement de l’artérite à cellules géantes : résultats d’une étude prospective, multicentrique de phase II (PHRC National HORTOCI)
Introduction L’arterite a cellules geantes (ACG) est une vascularite des gros vaisseaux habituellement traitee par corticoides. Ce traitement est remarquablement efficace mais doit etre donne a forte dose pendant 12 a 24 mois, ce qui est responsable d’une importante morbi-mortalite dans cette population âgee. Le tocilizumab (TCZ) est un anticorps monoclonal humanise dirige contre les recepteurs (soluble et membranaire) de l’interleukine-6 (IL-6). Son efficacite a recemment ete montree au cours du traitement de l’ACG [1] . Cependant, les donnees concernant l’evolution apres l’arret du TCZ manquaient dans cet essai therapeutique. De plus, la duree optimale de ce traitement couteux n’est pas c…
Immunologic effects of rituximab on the human spleen in immune thrombocytopenia
Abstract Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell de…
Impact du confinement dû au COVID-19 sur la prise en charge et le contrôle de l’artérite à cellules géantes
Introduction L’arterite a cellules geantes (ACG) est une maladie multifactorielle dont la pathogenie n’est pas encore totalement comprise [1] . Malgre tout, il existe une relation dynamique entre predispositions genetiques et facteurs environnementaux via des modifications epigenetiques ayant un role dans le declenchement et l’evolution de cette pathologie [2] , [3] . Le confinement du a l’epidemie de COVID-19 a cree une situation sans precedent entrainant un stress physique et psychologique important chez de nombreuses personnes. Par ailleurs, la pression mediatique importante quant a l’usage des corticoides qui sont souvent prescrits chez les patients atteints d’ACG, etait tres anxiogene …
Pathogénie de l’artérite à cellules géantes
Giant-cell arteritis (GCA) involves larges arteries, especially aorta and extra-cranial branches of external carotid. Histo-pathological lesions affect all the layers of the artery leading to a segmental and focal panarteritis with a polymorphic cell infiltrate including T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and an intimal hyperplasia. The pathophysiology of GCA is not fully understood. After dendritic cell activation in the adventitia, CD4T cells are recruited in the arterial wall and polarized into Th1 and Th17 cells that produce IFN-γ and IL-17. These cytokines activate macrophages, giant cells and smooth muscle cells inducing vascular …
Moving from Dermatomyositis Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody to Anti-Melanoma Differentiation-Associated Gene 5 Syndrome
International audience
Systematic retrospective study of 64 patients with anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy
T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease
International audience; IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy contro…
Efficacy and safety of dapsone as second line therapy for adult immune thrombocytopenia: A retrospective study of 42 patients.
Dapsone is recommended as a second line therapy in immune thrombocytopenia (ITP), but is underused because of its potential side effects. The medical charts of 42 ITP patients treated with dapsone (100 mg/day) were retrospectively reviewed in order to assess its efficacy and safety in daily clinical practice. The overall response rate was 54.8% (n = 22, with a complete response in 38.1%) with a median time to response of 29 days (24-41 days). Patients with complete response had shorter disease duration whereas no difference was observed between responders and non-responders regarding age, sex or previous treatments received. Importantly, after dapsone withdrawal, a sustained response was ob…
Is TNF-α really involved in giant cell arteritis pathogenesis?
Giant cell arteritis (GCA) is the most frequent vasculitis in people >50 years, and glucocorticoids (GC) remain the cornerstone of the treatment. However, this long-term treatment is responsible for numerous GC-related complications.1 Thus, reliable GC-sparing drugs need to be explored. Seror et al 2 have recently reported the inefficacy of adalimumab, a humanised anti-TNF-α therapy, as a GC-sparing drug in the treatment of GCA. These clinical results contrast with previous studies reporting a production of TNF-α by giant cells and macrophages in GCA lesions.3 However, recent advance in the knowledge of GCA pathogenesis have shown that macrophages and giant cells are not involved in the fir…
Does Tocilizumab Indeed Reduce the Frequency of Th17 Cells? Comment on the Article by Thiolat et al
Are IL-10+ regulatory Th17 cells implicated in the sustained response to glucocorticoid treatment in patients with giant cell arteritis? Comment on the paper of Espigol-Frigoleet al
We have read with interest the recently published paper of Espigol-Frigole et al 1 in which the authors confirmed that interleukin (IL)-17 is highly expressed in giant cell arteritis (GCA) lesions.1–3 They also demonstrated for the first time that IL-17 expression in temporal artery biopsies (TABs) was correlated with a better outcome. Among other interesting results, the identification of Foxp3+IL-17+ T cells by confocal microscopy in TAB made the authors to hypothesize that these cells could be induced regulatory T cells (Treg) that may facilitate the remission of the disease under steroid therapy. …
Simulation en santé et médecine interne : quel avenir ?
Simulation-based learning (SBL) is developing rapidly in France and the question of its use in the teaching of internal medicine (IM) is essential. While HAS encourages its integration into medical education, French Young Internists (AJI) set up a working group to reflect on the added-value of this tool in our specialty. Different sorts of SBL exist: human, synthetic and electronic. It enables student to acquire and evaluate technical skills (strengths, invasive procedures, etc.) and non-technical skills (relational, reasoning…). The debriefing that follows the simulation session is an essential time in pedagogical terms. It enables the acquisition of knowledge by encouraging the students' …
Giant cell arteritis-related aortitis with positive or negative temporal artery biopsy: a French multicentre study.
Objective: To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB).Method: Patients with GCA-related...
Physiopathologie des artérites à cellules géantes
Resume L’arterite a cellules geantes (ACG) et l’arterite de Takayasu sont deux vascularites granulomateuses affectant les vaisseaux de gros calibre dont la cause exacte n’est pas connue. Neanmoins, les mecanismes physiopathologiques impliques au cours de l’ACG sont de mieux en mieux identifies et ont permis l’emergence de nouvelles cibles therapeutiques comme le blocage de la signalisation de l’interleukine-6 (IL-6). Le facteur declenchant de ces vascularites n’est pas connu mais l’hypothese, jamais confirmee a ce jour, d’un agent infectieux activant les cellules dendritiques de l’adventice est privilegiee. Cette activation de la reponse immunitaire innee permet le recrutement et l’activati…
Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia
The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RT…
Associated arterial and venous cerebral manifestations in Behçet's disease
Behcet's disease is a rare multisystemic vasculitis with an etiology that is still unknown. Neurological manifestations may be seen in approximately 5-15% of patients, and both parenchymal and extraparenchymal neurological involvement has been described. When cerebral venous thrombosis (CVT) is the main extraparenchymal manifestation of Behcet's disease, the condition is then dubbed "angio-Behcet's syndrome". However, arterial involvement is extremely rare, with only one reported case of vasculo-neuro-Behcet's disease, characterized by both venous and intracranial arterial involvement - until now. This report is of two patients diagnosed with Behcet's disease characterized by the concomitan…