Search

Contexte : La réforme de la première année des études de santé définie dans le décret du 4 novembre 2019 a mis fin à la première année commune aux études de santé (PACES) pour introduire un nouveau système ayant pour objectif de diversifier l’accès aux formations de médecine, maïeutique, odontologie, pharmacie et kinésithérapie (MMOP-K) par différents parcours de formation antérieurs. À l’Université de Bordeaux a été mis en place un double système avec un parcours accès spécifique santé (PASS) et des licences accès santé (L.AS). La voie L.AS étant minoritaire en cette première année de mise en place de la réforme, nous avons centré notre analyse sur les étudiant·es en PASS en 2020–2021 et l’accès à la filière médecine. Méthodes : Cette première année de PASS a été évaluée au regard des résultats académiques aux épreuves écrites des deux semestres (nombre d’UE validées, validation/échec du PASS, admissibilité dans la filière médecine) et aux épreuves orales (réussite aux mini entretiens multiples, admission dans la filière médecine). Résultats et conclusion : Nous avons identifié le niveau scolaire à l’entrée à l’Université, mesuré par la mention au bac, comme étant le principal facteur de réussite pour la validation du PASS et la réussite à l’admission dans la filière médecine. Le déterminant social est également associé à la validation du PASS, indépendamment du niveau scolaire. Les résultats montrent également que l’hétérogénéité des résultats en fonction de l’option disciplinaire et du site géographique est essentiellement liée à des disparités de niveaux scolaires à l’entrée en PASS.

Aim: To describe the effects of a summertime pause (SP) in immunoglobulin replacement therapy (IgRT). Patients & methods: We conducted a prospective single-center observational study, including 44 patients undergoing intravenous IgRT between May and June 2019 in a French teaching hospital. Results: IgRT was interrupted in 23 patients from June to October. Patients who underwent an SP were older, more likely to have secondary immunodeficiency (SID) and received lower doses of immunoglobulin and more antibiotics during winter. Most patients who did not undergo an SP had severe primary immunodeficiency. The SP did not increase the risk of infection, improved the quality of life and reduced treatment costs. Conclusion: SP in IgRT is a safe practice and should be considered for patients with mild SID.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor–β axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin–dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue.

Background Guidelines that detail preventive measures against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and influenza are published annually in France to decrease the risk of severe infections in immunocompromised patients. We aimed at describing adherence to these guidelines by GPs in the management of their asplenic patients in France between 2013 and 2016. Method We conducted a multicenter retrospective study between January 2013 and December 2016 in three French hospitals: asplenic adults were identified and their GPs were questioned. A descriptive analysis was performed to identify the immunization coverage, type and length of antibiotic prophylaxis, number of infectious episodes, and education of patients. Results 103 patients were finally included in this study: only 57% were adequately vaccinated against Streptococcus pneumoniae or Neisseria meningitidis, 74% against Haemophilus influenzae type b, and 59% against influenza. Only 24% of patients received a combination of all four vaccinations. Two-thirds of patients received prophylactic antibiotics for at least 2 years. Overall, this study found that 50% of splenectomized patients experienced at least one pulmonary or otorhinolaryngological infection, or contracted influenza. Conclusions These data match those reported in other countries, including Australia and the United Kingdom, meaning a still insufficient coverage of preventive measures in asplenic patients. Improved medical data sharing strategies between healthcare professionals, along with educational measures to keep patients and physicians up to date in the prevention of infections after splenectomy would improve health outcomes of asplenic patients.

Introduction La sarcoidose est une maladie systemique pleomorphe caracterisee par la formation de granulomes dans divers organes. Meme si sa prevalence semble etre en augmentation, la localisation cardiaque est rare, mais particulierement grave. Le diagnostic et la prise en charge des sarcoidoses avec atteinte cardiaque reste mal standardise malgre les recommandations de la Heart Rhythm Society emises en 2014. Notre objectif etait de decrire le profil clinique, paraclinique, et evolutif de patients affectes d’une sarcoidose cardiaque et suivis dans notre centre hospitalier universitaire. Materiels et methodes Notre etude est retrospective et monocentrique. L’ensemble des patients presentant une sarcoidose avec atteinte cardiaque entre le 1er janvier 2000 et le 31 decembre 2018 ont ete inclus en deux temps ; une premiere selection a ete faite par recherche aupres du service « Programme de Medicalisation des Systemes d’Information », et du service de medecine nucleaire. Nous avons ensuite retenu les patients qui presentaient une atteinte cardiaque selon les criteres du ministere de la sante japonais ou de la Heart Rhythm Society avec sarcoidose extracardiaque prouvee histologiquement ; les patients dont le mode de revelation de la sarcoidose a ete l’atteinte cardiaque etaient inclus s’ils presentaient une association de signes cliniques et paracliniques evocateurs de sarcoidose cardiaque ou extracardiaque. Nous avons recueilli les donnees sociodemographiques, le mode de revelation de la sarcoidose, les caracteristiques cliniques et paracliniques de la sarcoidose cardiaque et des atteintes extracardiaques eventuellement associees, le traitement realise et l’evolution. Resultats Quatorze patients ont ete inclus dont 6 femmes et 8 hommes (sex-ratio F/H 0,75). L’âge moyen au diagnostic etait de 50 ans. Un seul patient avait une atteinte cardiaque isolee ; 12 patients presentaient au moins deux localisations associees a l’atteinte cardiaque ; les plus frequentes etaient ganglionnaires (13/14 patients, 93 %) et pulmonaires (10/14 patients, 77 %). Le diagnostic de sarcoidose a ete etabli sur une atteinte cardiaque initiale chez 6 patients. Chez 7 autres patients la sarcoidose a ete diagnostiquee du fait d’une une localisation extracardiaque, lors du bilan d’extension initial chez 2 d’entre eux, et au cours d’une manifestation cardiaque tardive chez les 5 autres. Neuf patients repondaient aux criteres de diagnostic japonais, et 12 aux criteres de la Hearth Rhythm Society. Le symptome le plus frequent etait la dyspnee (n = 9). L’ECG etait anormal dans 12 cas parmi les 13 disponibles : troubles de la conduction (n = 9), troubles du rythme (n = 11). L’ETT etait anormale chez 10 patients parmi les 14 ; les anomalies les plus frequentes etaient l’alteration de la fraction d’ejection du ventricule gauche (n = 6) et l’hypokinesie (n = 4). L’IRM cardiaque etait toujours pathologique parmi les 12 patients evalues ; les anomalies les plus frequentes etaient la prise de contraste myocardique tardive (n = 11) et l’hypokinesie (n = 7). La TEP scanner realisee chez dix patients etait a chaque fois anormale : hyperfixation myocardique (n = 6) et infiltration tissulaire cardiaque (n = 3). Le traitement comportait des corticoides associes a un immunosuppresseur dans 11 cas : methotrexate (n = 6), mycophenolate mofetil (n = 4) et endoxan (n = 1) ; 3 patients ont recu une corticotherapie seule. L’evolution a ete favorable chez 11 patients ; un patient a presente un echec therapeutique ; 2 patients ont presente une rechute. Conclusion Les sarcoidoses cardiaques restent rares, et sont rarement isolees. Les symptomes et les anomalies des examens de premiere intention sont tres peu specifiques voire absents. Dans ces circonstances, la realisation d’une IRM cardiaque ou d’une TEP scan doivent etre discutes. Si la prise en charge therapeutique est mal codifiee, dans notre serie l’association d’une corticotherapie a un traitement immunosuppresseur induit un taux de reponse de 78 % environ. Ces resultats doivent etre ponderes du fait d’un recul limite (18 mois).

International audience; no abstract

International audience; Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.

OBJECTIVE To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators. METHODS A total of 203 SSc patients and 30 healthy donors were prospectively enrolled between 2012 and 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analyses were performed on skin biopsy sections from 18 SSc patients and 5 healthy donors. Serum thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay in the entire cohort. HDMECs and fibroblasts were purified from biopsy sections. Extracellular matrix production by cultured fibroblasts was assessed by real-time quantitative polymerase chain reaction. RESULTS Serum TSLP levels were significantly increased in SSc patients compared to healthy donors (P

Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Persistent or chronic immune thrombocytopenias (P/C-ITP) are acquired blood disorders lasting more than 3 months or 1 year, respectively. The pathogenesis of these disorders is thought to be immunological. We hypothesized that some patients with P/C-ITP might have an intrinsic megakaryopoiesis defect. We identified a group of P/C-ITP patients with acquired isolated mild thrombocytopenia (30-100 × 10(9) /l), undetectable anti-platelet antibodies, negative autoimmune investigations and no need for treatment. We examined in vitro megakaryocyte differentiation and compared these patients' results with those of acute-ITP patients and healthy controls. No difference in proliferation, ploidy or expression of surface markers was found. In contrast, P/C-ITP patients had significantly fewer proplatelet-forming megakaryocytes. This novel observation demonstrated that some patients diagnosed with P/C-ITP have an intrinsic megakaryopoiesis defect independent of the bone-marrow environment. Further investigations are needed to dissect mechanisms underlying this impaired proplatelet formation in these patients.

Resume Propos L’hydroxyuree (HU) est une chimiotherapie antimetabolite frequemment utilisee dans le traitement des syndromes myeloproliferatifs chroniques. Ce traitement est habituellement bien tolere par les patients, mais des cas de fievre induite par l’HU ont ete rapportes dans la litterature. L’objectif de ce travail etait de definir les caracteristiques cliniques et biologiques d’hyperthermie induite par l’HU. Methodes Etude retrospective de quatre cas d’hyperthermie induite par l’hydroxyuree pris en charge dans un service de medecine interne entre 2006 et 2012. Les cas cliniques sont associes a une revue de la litterature dans les bases de donnees de Pubmed et de la Cochrane. Resultats Trente-huit cas, incluant notre serie personnelle, d’hyperthermie induite par l’hydroxyuree ont ete rapportes depuis 1981. L’âge moyen etait de 65 ± 10,9 ans. Il y avait 50 % d’homme. La mediane de survenue de l’hyperthermie etait de 21 jours. La mediane de temperature etait de 40 °C, cliniquement bien toleree. Le syndrome inflammatoire biologique etait modere avec une CRP moyenne a 131 ± 92 mg/L. Un traitement d’epreuve par antibiotherapie probabiliste etait realise chez 34 % des patients. Un test de reintroduction etait realise chez 50 % patients, un seul patient avait un test de reintroduction negatif. Un tiers des patients presentait une atteinte hepatique ou pulmonaire associee. La fievre regressait a l’arret du traitement avec une mediane de 24 heures. Conclusion Les fievres induites par l’hydroxyuree sont stereotypees. Un bilan infectieux standard doit etre propose. Si l’enquete infectieuse est negative, un arret precoce du traitement permet une regression rapide de la symptomatologie permettant de confirmer le diagnostic.

Aim To date, neither the benefit of mycophenolic acid (MPA) therapeutic drug monitoring (TDM), the prodrug of mycophenolate mofetil (MMF), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods MPA areas under the concentration–time curves between 0 and 12 h, 12 h trough concentrations and pre-dose concentrations (C0) were determined for 23 patients with SLE and 21 with systemic vasculitis. The relationship between patients' pharmacokinetic (PK) variables and their clinical outcomes during follow-up were analyzed. Results In both autoimmune diseases, at PK assessment, median MPA C0 for patients with uncontrolled disease was significantly lower than that of patients with stable disease or in remission, 1.6 mg l–1 (IQR 0.9–2.1 mg l–1) vs. 2.95 mg l–1 (IQR 1.38–3.73 mg l–1) for SLE (P = 0.048) and 1.55 mg l–1 (IQR 0.98–2.18 mg l–1) vs. 3 mg l–1 (IQR 2.2–4.4 mg l–1) for vasculitis (P = 0.016). According to our receiver operating characteristics curve analysis, a C0 threshold of 2.5–3 mg l–1 was best able to discriminate a flare (SLE: 88% sensitivity, 80% specificity; vasculitis: 100% sensitivity, 90% specificity). Patients with C0 ≥ 2.5–3 mg l–1 at inclusion had better clinical outcomes during the 12 months following PK assessment. Conclusion Provided that the benefit of TDM in patients with autoimmune diseases could be confirmed by randomized, controlled trials, it might be based on the C0 measured approximately 12 h post-dose.

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide (TLCO) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning TLCO into membrane conductance (diffusing capacity) for carbon monoxide (DMCO) and alveolar capillary blood volume (VC) through combined measurement of TLCO and transfer factor of the lung for nitric oxide (TLNO) is more effective to identify pulmonary hypertension in SSc patients compared with TLCO alone. Here, the objective was to determine whether combined TLCO–TLNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than TLCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. TLCO, TLNO and VC were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for TLCO (0.82, 95% CI 0.79–0.85) and TLNO (0.80, 95% CI 0.76–0.83), but lower for VC (0.75, 95% CI 0.71–0.78) and DMCO (0.66, 95% CI 0.62–0.70).Compared with TLCO alone, combined TLCO–TLNO does not add capability to detect pulmonary hypertension in unselected SSc patients.

International audience; Bortezomib is an active agent in AL amyloidosis and responses to this drug in combination with cyclophosphamide and dexamethasone are both rapid and deep. Here we present an international, multicenter series of 60 patients with Mayo Clinic stage III cardiac amyloidosis to assess the impact of this regimen in improving outcomes in this poor-risk group. The median follow-up for the entire cohort is 11.8 months. The overall response rate was 68%. In a landmark analysis, examining patients who survived more than 3 months, the overall response rate was 86%. A cardiac response was seen in 32% of patients. The estimated 1-year survival rate for the whole cohort was 57% and 24 patients (40%) died while on therapy. Although unable to save the poorest risk patients, the combination of bortezomib, cyclophosphamide and dexamethasone can achieve a high number of hematologic and cardiac responses, likely improving overall survival and justifying a prospective trial.

Introduction The Bentall procedure is a cardiac surgery involving graft replacement of the aortic valve, aortic root and ascending aorta. Graft infection after Bentall's procedure (BGI) is infrequent but severe, and often difficult to diagnose and treat. Patients and Methods A retrospective cohort study was performed using the Bordeaux endocarditis database of adult patients admitted to the Bordeaux University Medical Hospital for BGI between 2008 and 2014. Published case reports were identified in the literature. Results We identified 10 BGI patients in the database and 13 in the literature. The majority of infections were late-onset (20/23) and occurred as a result of gram positive cocci bacterial infection (16/22). Detailed diagnoses of the described BGI were determined using echocardiography, computed tomography (CT) and positron emission tomography/CT (PET/CT). Labeled-leukocyte scintigraphy was not reported in any case. Prolonged antibiotic therapy and surgery were found to be the treatment of choice for BGI; however it was not always possible to perform a surgical intervention. Clinical relapses occurred even with a negative PET/CT, while PET/CT consistently positive for BGI occurred in the absence of clinical relapse. This suggests that the use of PET/CT for follow-up is questionable. Conclusion Diagnosis of BGI is difficult, due to the combination of clinical, biological, and radiological observations obtained through transesophageal echocardiography and CT. PET/CT is an alternative method to diagnosis BGI, but its impact on clinical management remains unclear. Current data suggests that if surgical replacement of the prosthesis is not possible, patients should be treated with prolonged antibiotic therapy.

Resume Interet du travail Depuis 2011, les etudiants classes aux epreuves classantes nationales (ECN) font leur choix d’exercice futur parmi 11 disciplines avec la selection precise d’une specialite medicale ou chirurgicale. Notre objectif etait de decrire le choix des etudiants a l’issue des ECN quant a leur future discipline d’exercice et leur future ville de formation en troisieme cycle des etudes medicales. Methodes Nous avons analyse le fichier Excel® fourni par l’Agence regionale de sante d’Aquitaine a l’issue du choix des etudiants apres les ECN 2012. L’analyse par rang median national a ete realisee pour le choix des disciplines et des villes de formation. Pour les specialites (medicales ou chirurgicales) et la medecine generale, une analyse comparative en fonction des densites medicales regionales a ete effectuee selon les donnees du Conseil de l’Ordre des medecins. Resultats Par rang median national de choix, les six premieres disciplines choisies etaient l’ophtalmologie, la nephrologie, la medecine interne, la radiologie, la cardiologie et la dermatologie. Les etudiantes etaient plus attirees par la gynecologie medicale ou obstetrique, la pediatrie ou la dermatologie ; les etudiants par la neurochirurgie, la chirurgie generale, la medecine nucleaire et la cardiologie. Les villes les plus prisees selon le rang median national de choix etaient Lyon, Montpellier et Ile-de-France. La plupart des etudiants (59 %) ont change de ville pour acceder a une specialite. En medecine generale, 56 % des etudiants sont restes dans leur ville de formation. Perspectives Notre etude permet de donner un objectif concret aux etudiants en deuxieme cycle des etudes medicales, et d’apporter des donnees supplementaires en matiere de gestion de la demographie medicale.

Introduction Le port de prothese articulaire peut se compliquer d’intoxication aux metaux lourds secondaire a leur usure [1] . Observation Une femme de 69 ans est prise en charge pour le remplacement d’une prothese de hanche gauche composee de ceramique et d’alumine en faveur d’une prothese constituee de metaux (chrome, cobalt et molybdene), en raison d’une instabilite. Au cours de l’annee suivante, la patiente consulte a trois reprises pour douleurs en rapport avec des luxations de la hanche gauche. La reduction est realisee chaque fois sans difficulte. Au decours du troisieme episode, elle presente une sciatalgie. Elle est hospitalisee six mois plus tard pour une alteration de l’etat general. Elle boite et se plaint de douleurs majeures de la hanche gauche. Une collection est palpable en regard de l’articulation. Il existe, de facon bilaterale, une cecite par œdeme papillaire et une surdite de perception. Elle developpe egalement une confusion et des troubles cognitifs en faveur d’une encephalopathie. L’echographie articulaire met en evidence une collection autour de la prothese de hanche gauche. L’imagerie par resonance magnetique (IRM) revele des lesions au niveau des os, des articulations, du materiel prothetique et une volumineuse collection affectant les tissus musculaires adjacents. Au cours de la ponction de la collection, un liquide noirâtre est preleve. Outre la recherche d’agents infectieux, des dosages des metaux composant la prothese sont realises. Le liquide est sterile. Les concentrations des metaux sont elevees dans le liquide de ponction de la collection, mais aussi dans le serum et les urines. Le diagnostic d’intoxication aux metaux liee a une degradation du materiel prothetique est retenu. Le centre antipoison propose la depose immediate de la prothese et une chelation intraveineuse. Au cours de la chirurgie, la tete de la prothese presente une usure importante avec une perte de 18 g de metal. Une collection de 500 ml d’un liquide noirâtre est extraite. L’evolution postoperatoire est marquee par l’aggravation de l’encephalopathie toxique probablement favorisee par la diffusion des metaux au cours de la prise en charge chirurgicale. La ponction lombaire revele la presence de metaux dans le liquide cephalorachidien et l’IRM cerebrale des anomalies des noyaux gris. La chelation est debutee. Six mois apres la depose de la prothese, deux perfusions de chelateurs ont ete realisees en milieu hospitalier. La patiente a repris 13 kg. La surdite est en regression. Les troubles de l’acuite visuelle s’ameliorent peu. Les troubles cognitifs diminuent mais persistent a minima, de meme que les anomalies de l’IRM cerebrale. La chelation dont le benefice est favorable est poursuivie. Conclusion Outre les risques d’infection, de perforation ou de malposition, il existe d’autres complications liees aux dispositifs medicaux metalliques implantables. L’intoxication aux metaux lourds peut se traduire par des manifestations systemiques. La collaboration avec les toxicologues est essentielle pour l’optimisation de la prise en charge globale de ces metalloses.

Romiplostim is a thrombopoietin-receptor agonist approved to treat chronic immune thrombocytopenia (ITP). We treated eight patients with acute or persistent primary ITP, severe clinical bleeding, and resistance to corticosteroids and/or intravenous immunoglobulins (IVIg). Romiplostim, initially administered at 2 or 3 μg/kg/week, was subsequently increased to achieve and maintain platelet-count responses and control bleeding. Seven patients' platelet counts rose above 30 G/L, representing ≥twofold increases, within a median of 14 days after 1-5 infusions. The weekly dose reached 9 μg/kg at week 5 for three patients; the other patients' ITPs were controlled with ≤6 μg/kg/week. No thromboembolic events occurred. Five patients received rituximab concomitantly with romiplostim, four of whom could stop romiplostim within 2 months, thereby demonstrating rituximab efficacy. All three patients treated with romiplostim alone required maintenance therapy. Thus, romiplostim represents an alternative for patients with severe acute or persistent ITP refractory to conventional therapy.

Large granular lymphocyte leukemia (LGL) is a hematologic disorder characterized by a monoclonal expansion of large lymphocytes containing azurophilic granules with a T CD3(+)CD57(+) or Natural Killer (NK) CD3(-)CD56(+) phenotype. The World Health Organization (WHO) classification identifies three entities: the T LGL, the chronic lymphoproliferative disorder of NK-cells, and the aggressive NK-cell leukemia. T LGL and chronic lymphoproliferative disorder of NK-cells are indolent diseases frequently associated with cytopenias and a wide spectrum of auto-immune manifestations. Neutropenia can lead to recurrent bacterial infections, which represent an indication of initiating a treatment in most of the cases. Immunosuppressive therapies are usually used in this context. In contrast, aggressive NK-cell leukemia follows a fulminant course with a poor prognosis because patients are refractory to most of the treatments. There is now a considerable interest in the pathophysiology of the disease with the perspective of new therapeutic options.

A higher chronic expansion of effector cytotoxic CD8(+)DR(+) T-lymphocytes has been reported in common variable immunodeficiency (CVID) patients with complications such as splenomegaly, autoimmune disease and/or granulomatous disease. In order to document the features associated with this T cell activation involving the CD8(+) T-compartment, we examined the diversity of the alpha/beta TCR repertoire of the patient's CD8(+) T-lymphocytes using the qualitative analysis of the CDR3 lengths (Immunoscope). Ten CIVD patients were enrolled in this study, four without complications (Group 1), six with complications (Group 2). All patients exhibited non-gaussian altered CDR3 length distributions, albeit to different extent within the different Vβ families. CVID patients with activated CD8(+) T-cells show a reduction of their TCR repertoire diversity which is more severe in patients with complications. Viral reactivations such as CMV are suspected to be part of the mechanisms underlying immunosenescence.

Background Nontuberculous mycobacteria (NTM) are environmental organisms associated with a range of infections. Reports of NTM epidemiology are mainly focused on pulmonary infections and isolations, and extrapulmonary infections are less frequently described. Methods We conducted a retrospective study of NTM infections at the Bordeaux University Hospital, France, between January 2002 and December 2013. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. Results In our setting, 170 patients were included. Pulmonary cases predominated (54.1%), followed by skin and soft tissue infections (22.9%), disseminated cases (10.6%), lymphadenitis (7.7%), bone and joint infections (2.9%) and the remaining 1.8% catheter-related infections. Overall, 16 NTM species were isolated. Mycobacterium avium (31.8%) and M. intracellulare (20%) were the most common species identified, followed by M. marinum (13.5%), M. kansasii (10.6%), M. xenopi (9.4%), rapidly growing mycobacteria (9.4%) and other slowly growing mycobacteria (5.3%). In general, NTM isolates were largely prevalent in people older than 50 (62.4%); patients aged 1–10 year-old exclusively yielded M. avium from lymph nodes, almost cases having being diagnosed after 2007. Among the 121 patients with complete follow-up, 78 (64.5%), 24 (19.8%), and 19 (15.7%) were cured, experienced relapse, or died, respectively. Conclusion In our study, extrapulmonary NTM infections represented almost half of cases, consisting mainly in skin and soft tissue infections. The increase lymphadenitis cases in children after 2007 could be linked to the cessation of mandatory BCG vaccination in France. We observed similar cure rates (64%) between pulmonary and extrapulmonary infections.

Resume Propos Le lymphome a grandes cellules B intravasculaire (LBIV) est une forme de lymphome malin non hodgkinien rare et grave, se developpant au sein de la lumiere des petits vaisseaux de l’organisme, de presentation systemique et polymorphe, rendant le diagnostic difficile et retardant la prise en charge urgente. Patients et methodes Nous presentons ici trois cas atypiques de patients atteints de LBIV, a la lumiere desquels nous ferons une revue de la litterature. Resultats Le premier cas presente une thrombopenie peripherique avec destruction plaquettaire splenique, se completant secondairement par l’apparition d’un syndrome interstitiel pulmonaire ; le deuxieme est celui d’un patient d’origine africaine (premier cas de LBIV chez un patient noir) ; le troisieme est l’un des rares cas repertories de la maladie associes a un syndrome d’activation macrophagique chez un patient occidental. Conclusion Le LBIV est une maladie systemique et tres polymorphe, qui de ce fait rentre dans le champ d’activite de l’interniste, et dont la bonne connaissance devra permettre une prise en charge rapide et adaptee.

Resume Introduction La necrose medullaire, caracterisee par une necrose des progeniteurs hematopoietiques, des ilots adipocytaires et de la trame de reticuline, est une pathologie tres rare. Observation Nous rapportons l’observation d’une patiente de 62 ans admise en reanimation pour une necrose medullaire etendue compliquant l’evolution d’une thrombocytemie essentielle associee a un choc septique sans germe retrouve, amenant rapidement au deces dans un contexte de defaillance multiviscerale. Il s’agit, a notre connaissance, du deuxieme cas rapporte dans la litterature a ce jour. Sa presentation clinique est aspecifique et associe douleurs osseuses et fievre, et parfois un syndrome d’insuffisance medullaire. La biologie peut montrer des cytopenies diversement associees, une elevation des LDH et des phosphatases alcalines osseuses. Le diagnostic est histologique, obtenu apres biopsie osteomedullaire. La necrose est dite etendue si elle concerne plus de 50 % du cylindre biopsique. Cette pathologie est associee dans 90 % des cas a une hemopathie maligne (notamment les leucemies) ou a une tumeur solide le plus souvent gastro-intestinale ou pulmonaire. D’autres etiologies regroupent la drepanocytose ou le syndrome catastrophique des anticorps antiphospholipides, la thrombocytemie essentielle etant exceptionnellement responsable d’une necrose medullaire. Conclusion Toutes causes confondues, le pronostic de la necrose medullaire etendue est generalement sombre sauf en cas de traitement precoce et intensif, notamment chez les patients drepanocytaires chez qui peut s’observer une regeneration medullaire complete.

Summary Introduction The recent discovery of the Janus Kinase 2 (JAK2V617F) mutation, an indicator of clonal expansion, has widely modified the diagnostic work-up of myeloproliferative disorders. However, histopathologic criteria of the WHO classification, focused on megakaryocytes abnormalities, have taken a central role in the diagnosis of essential thrombocytemia (ET), particularly to distinguish it from the prefibrotic myelofibrosis (PMF) evolving to a clinic myelofibrosis unlike true ET. The aim of our study is to evaluate inter-observer reproducibility and prognostic implications of these pathological criteria comparing diagnoses with clinical and biological follow-up. Methods Forty-four patients presenting with isolated thrombocytemia were retrospectively evaluated. All patients were initially diagnosed with ET based on the PVSG classification from 1997. The initial bone marrow biopsy specimens were re-evaluated using the Thiele pathological classification: true ET, prefibrotic myelofibrosis (PMF) and early myelofibrosis. Patients were followed for a median of 6 years. Results Our population includes three patients with polycythemia vera and 41 patients with true ET. Based on clinical and biological follow-up, diagnoses were changed to idiopathic myelofibrosis in four of six patients with “early” myelofibrosis (66.7%), but in only one of 14 patients with PMF (7.15%). In contrast, the diagnosis of true ET was not changed in the 21 cases. Inter-observer reproducibility for pathological classification was 100%. Conclusion In this study, our diagnostic methodology based on the clinico-biological follow-up, which has not been evaluated in previous studies, calls into question the diagnostic value of the pathological criteria in PMF.

Introduction Liquid chromatography coupled with mass spectrometry for the quantification of raltegravir in human plasma and peripheral blood mononuclear cells has been developed. Methods Sample preparations were based on a fully automated solid-phase extraction process. Mass spectrometric data were acquired in a single-ion monitoring method. Raltegravir and quinoxaline, the internal standard, were well separated in a gradient mode over 15 min. Key findings Validation study exhibited excellent linearity, with good intra- and inter-day precision and accuracy. Conclusions The assay was successfully applied to the raltegravir quantification in HIV-infected patients.

We report a fairly special case of lymphocytic myocarditis progressing to a fibrotic stage, described using multimodality imaging and confirmed on histopathology. This paper presents an uncommon diagnosis with a probable guarded prognosis.

Background & Aims Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX–liver toxicity. The aim of this case–control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX. Methods Consecutive adults with various benign inflammatory diseases were prospectively assessed using FibroScan and FibroTest when they were treated with MTX (cases) or before beginning treatment (controls). Results Among 518 included patients, 44 patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver fibrosis. In a multivariate analysis, factors associated with abnormal markers of liver fibrosis were the body mass index >28kg/m2 and high alcohol consumption. Neither long MTX duration nor cumulative doses were associated with elevated FibroScan or FibroTest results. Conclusions Severe liver fibrosis is a rare event in patients treated with MTX and is probably unrelated to the total dose. Patients with other risk factors for liver disease should be closely monitored with non-invasive methods before and during MTX treatment.

Mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), is used to treat systemic lupus erythematosus (SLE). MMF and EC-MPS pharmacokinetics were examined to devise guidance for therapeutic drug monitoring (TDM) for SLE patients with normal renal function.This observational study included 21 patients receiving MMF (1000 mg twice daily) and 14 taking EC-MPS (720 mg twice daily). MPA AUC between 0 and 12 h (AUC(0-12h)), C(max), T(max), and 12-h trough concentrations (C(12h)) were determined.Means of dose-normalized MMF- or EC-MPS-MPA C(max) were 64.6 +/- 25 and 61.4 +/- 27.1 h mg/l, respectively. MPA T(max) for EC-MPS was longer and more variable than for MMF. MMF-MPA AUC(0-12h) and C(12h) were correlated (r = 0.78, p = 0.0001), but EC-MPS-MPA C(max) and single concentrations were weakly correlated. A limited-sampling strategy (LSS) combining C(max) and C(12h) gave satisfactory predictive performance to estimate MPA AUC(0-12h) after EC-MPS administration.For TDM in SLE patients with GFR60 ml/min/1.73 m(2), C(12h) after MMF ingestion could predict MPA AUC(0-12h), while an LSS around T(max) should be used for patients on EC-MPS.

Resume Introduction Les lymphomes spleniques de la zone marginale (LSZM) sont rares et volontiers associes a des manifestations auto-immunes parfois revelatrices. Si les cytopenies (anemie, thrombopenie) auto-immunes sont les plus frequentes et orientent facilement le diagnostic devant une splenomegalie d’allure tumorale, d’autres manifestations ou d’authentiques maladies auto-immunes sont parfois au premier plan. Methodes Nous rapportons six observations de LSZM associe a des manifestations auto-immunes variees, recensees de facon retrospective sur une periode de cinq ans. Resultats Les manifestations auto-immunes compliquent l’evolution d’un LSZM connu dans deux cas et conduisent au diagnostic de LSZM dans quatre cas. Il s’agit de cytopenies auto-immunes dans trois cas (deux anemies hemolytiques et une pancytopenie), d’une thyroidite auto-immune dans deux cas, d’un lupus systemique et d’une maladie de Still. Des anticorps antinucleaires sont presents au 1/250 sans manifestations lupiques dans trois cas et au 1/32 000 dans le cas de lupus. Les anticorps anti-DNA natifs sont toujours negatifs. Un anticoagulant circulant de type lupique est present dans deux cas, associe a une thrombose portale apres splenectomie dans un cas. Une hypogammaglobulinemie est presente dans un cas et une immunoglobuline monoclonale dans trois cas. Une splenomegalie est presente dans tous les cas. L’immunophenotypage des lymphocytes B circulants est typique dans cinq cas sur six. La biopsie osteomedullaire montre un infiltrat lymphomateux dans cinq cas sur six. Ces deux examens permettent le diagnostic du lymphome dans cinq cas, l’examen anatomopathologique de la piece de splenectomie dans un cas. La serologie de l’hepatite C est negative dans tous les cas. Conclusion Les LSZM sont volontiers associes a des cytopenies auto-immunes mais s’accompagnent parfois d’authentiques maladies auto-immunes (lupus, maladie de Still) alors meme que le syndrome tumoral est discret. Dans ce cas, des elements atypiques (splenomegalie, hypogammaglobulinemie, monoclonalite, auto-immunite multiple) doivent alerter le clinicien.

Introduction Peu de biotherapies ont demontre une efficacite dans le lupus erythemateux systemique (LES) lors de leur developpement clinique. Seul le belimumab, anticorps anti-BLYS, indique chez les patients ayant un LES actif a obtenu une AMM. Cependant, les resultats des etudes BLISS-52/76 ont montre une efficacite clinique modeste. L’ASMR IV octroye au belimumab ne permet pas une inscription sur la liste des medicaments rembourses en sus de la T2A. Le belimumab etant une biotherapie onereuse, la valeur du GHS (groupe homogene de sejour) ne prend pas en charge le cout du traitement. Afin de permettre l’acces aux therapies innovantes, le belimumab est finance par l’etablissement de sante, centre de reference des maladies auto-immunes (MAI). Dans un contexte de maitrise des depenses de sante et au vu du cout en constante augmentation, l’acces au traitement devient problematique. L’objectif de ce travail est de realiser une analyse retrospective des prescriptions de belimumab, d’evaluer la reponse et le cout du traitement. Patients et methodes Chaque initiation de belimumab a fait l’objet d’une validation en RCP, d’une analyse pharmaceutique et d’un accord de financement par la Commission du Medicament, sous-commission de la CME. L’analyse retrospective des prescriptions comprend les caracteristiques des patients, le nombre de lignes anterieures, les traitements de fond associes et le schema posologique. L’activite de la maladie a l’instauration du traitement a ete estimee avec le score SELENA-SLEDAI. La reponse a ete evaluee au bout de 6 mois de traitement. Le cout du traitement a ete calcule avec le prix des flacons necessaires pour la preparation d’une poche. Resultats Au total, 11 patients ont ete inclus entre juillet 2014 et aout 2017, d’âge moyen 49 ± 11 ans et de sexe feminin. A l’instauration du belimumab, 100 % des patients presentaient un LES avec atteinte articulaire et une anciennete moyenne du LES de 13 ± 11 ans. Les patients presentaient les criteres suivants : anticorps anti-ADN natif 64 % (7/11), hypocomplementemie 27 % (3/11), arthrites ( > 2 articulations douloureuses) 91 % (10/11), proteinurie pathologique (0,5 a 2 g/24 h) 45 % (5/11), alopecie 9 % (1/11), pericardite 9 % (1/11), cephalees persistantes 9 % (1/11). Le score SELENA-SLEDAI moyen etait de 9 ± 3 et 91 % (10/11) des patients avaient un score ≥ 6. Le nombre moyen de traitements anterieurs etait de 5 ± 2 [corticoides : 100 % ; antimalarique : 91 % ; immunomodulateurs : 82 % ; immunosuppresseurs : 82 % ; …]. Au moins un traitement standard anti-lupique a ete associe en traitement de fond [antimalarique : 64 % ; corticoides : 55 % ; immunosuppresseurs : 36 % ; …]. La posologie de 10 mg/kg avec une intercure de 4 semaines a ete respectee pour tous les patients, une seule patiente a beneficie d’une diminution de dose pour intolerance (asthenie et troubles digestifs). Chez 8 patients, la reponse au traitement a ete evaluee au bout de 6 mois. Le traitement a permis d’obtenir une remission ou stabilite de la maladie chez 88 % (7/8) d’entre eux. Un patient a stoppe le traitement pour inefficacite. Le nombre de cures moyen recu par patient est de 13 ± 11. Le cout moyen d’une cure de belimumab est de 618 ± 138€. En 2014, le cout des cures de belimumab s’eleve a 7646€ (n = 1 patient), 20 444€ en 2015 (n = 2), 31 064€ en 2016 (n = 5). A ce jour, le cout du traitement en 2017 est de 41 017€ (n = 11). Le cout total du belimumab pour notre centre est de 100 170€ depuis 2014. Conclusion Le belimumab est prescrit en association a un traitement de fond aux patients ayant un LES resistant a de nombreuses lignes therapeutiques. Le schema posologique est respecte. Un seul patient ne presentait pas une activite elevee de la maladie, la prescription de belimumab se justifie par une contre-indication aux traitements standards. Au total, 10 prescriptions sur 11 entrent dans le cadre de l’AMM. Malgre une baisse du prix des flacons de belimumab, le cout pour l’etablissement est en constante augmentation en raison d’une hausse du nombre de patients traites et pour lesquels une reponse est maintenue. Compte-tenu du benefice clinique et de l’utilisation croissante de ce traitement, des strategies de positionnement et financement de ce medicament devraient etre proposees, en particulier dans les centres de reference des MAI, pour assurer l’acces au traitement.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan involvement characterized by an immune response against nuclear components. SLE patients experience a waxing and waning disease course and exhibit a wide array of clinical manifestations, reflecting the systemic nature of the disease. Environmental triggers such as viruses are likely to act in the context of susceptibility genes, including genes involved in antigen/immune complex clearance, lymphoid signalling, or apoptosis, among several others, explaining why the pathogenesis of this disease remains largely uncovered. The abnormal activation of the innate immunity is central to SLE physiopathology. Dendritic cells activation and unabated secretion of IFN-alpha are the key features of the disease through their involvement in the capture and the presentation of nuclear material to the autoreactive adaptive arm (T and B lymphocytes) leading to the subsequent production of anti-nuclear autoantibodies. In this line, numerous studies have demonstrated the prominent role of immune complexes deposition throughout the body which directly can induce inflammation and tissue damage. However, animal models and recent human studies support the concept that other effector pathways including cytotoxic T-lymphocytes could be involved in SLE pathogenesis through their ability to migrate and/or target specifically different tissues. The aim of this review is not to provide a comprehensive review of the SLE pathophysiology but rather to give an overview of the immunological abnormalities associated to SLE. The treatments that are currently used or that are in development to fight against abnormal immune response in SLE will be detailed. The genetics of SLE is not the scope of this review.

International audience; BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. METHODS: Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. RESULTS: The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.

Liquid chromatography coupled with mass spectrometry for the determination of total and unbound mycophenolic acid and its major metabolite in human plasma has been developed. Sample preparations were based on a fully automated solid-phase extraction process and ultrafiltration. Mass spectrometric data were acquired in a single-ion monitoring method. The analytes and nevirapine (internal standard) were well separated in an isocratic mode over 8 min. Validation study exhibited excellent linearity, with intra- and inter-day precision and accuracy of less than 12%. The assay was successfully applied to the pharmacokinetic study of mycophenolic acid in patients with autoimmune diseases.

Background HIV type-1 (HIV-1) has been shown to be frequently transmitted by acutely infected patients. We investigated the relationship between the dynamics of HIV-1 transmission within recently infected patients, the HIV-1 variability and the transmission of antiretroviral drug resistance. Methods We included patients infected between 1996 and 2006, with a plasma sample obtained Results Genotypic resistance was detected in 37/263 (14.1%) patients. Patients were infected by HIV-1 clade B in 222 (84%) cases and with non-B subtypes in 41 (16%). A total of 80 (30.4%) RT sequences were segregated in 24 clusters with bootstrap values >98% for 22 clusters. The frequency of grouping in clusters was higher within B sequences compared with non-B sequences (35.1% versus 4.9%; P-4). Drug-resistant isolates were retrieved in only 3 clusters, but the prevalence of resistance in clustering viruses (10/80, 12.5%) was not different than in isolated sequences. Conclusions The segregation into clusters suggested frequent forward transmission events in patients infected with HIV-1 subtype B, including the possibility of transmission of drug-resistant isolates. These findings warrant increasing prevention efforts and serological screening in the at-risk populations.

Kikuchi-Fujimoto disease (KFD), first described independently by Kikuchi and Fujimoto in 1972, is a subacute necrotizing lymphadenitis of unknown cause. Although most frequent in young Asian women, KFD has a worldwide distribution. Clinically, KFD is characterized by lymphadenitis of one or more lymph nodes, predominantly in the posterior cervical region, fever, and leukopenia in up to 50% of cases. Extranodal manifestations can occur, especially skin lesions and aseptic meningitides. Diagnosis is usually confirmed by analysis of samples from an excisional biopsy of the affected nodes. Histologically, the lesions affect the cortical and paracortical areas of the node. Characteristic features include focal necrosis predominantly in the paracortical region with abundant karyorrhectic debris and atypical mononuclear cells around the necrotic zone (crescent-shaped histiocytes, plasmacytoid monocytes, and small lymphocytes and immunoblasts, mostly CD3(+)/CD8(+)), most often with an intact lymph node capsule, an absence of neutrophils, and a paucity of plasma cells. KFD has been classified into three histological subtypes and is thought to progress from the proliferative type (> 50%) to the necrotizing type (30%) and finally resolve into the xanthomatous type (< 20%). Differential diagnoses should include malignant lymphoma, infectious diseases such as toxoplasmatic lymphadenitis, tuberculous lymphadenitis and cat scratch disease, and systemic lupus erythematosus (SLE). The cause of KFD is unknown: a viral infection has been suggested, but not demonstrated, possibly involving human herpes virus 8 or Epstein-Barr virus. Apoptotic cell death plays a role: proliferating CD8(+) T-lymphocytes act as both killers and victims in the apoptotic process via Fas and perforin pathways. The course is usually benign with resolution in a few months with the use of antiinflammatory drugs. Regular follow-up is required because SLE may develop several years after the onset of Kikuchi-Fujimoto disease.

Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy.

Innate immunity is directly implicated in the pathophysiology of lupus through the dendritic cell system and the activation by immune complexes of some toll-like receptors (TLR). Interferon-alpha plays a key role in the pathophysiology of lupus and represents a promising target for immune therapy. Dendritic cells are activated and able to capture large quantities of nuclear antigen-containing bodies to stimulate specific adaptive immune response.

Objective Recent studies have revealed a potential implication of CD8+ T lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) through their ability to induce tissue damage. The aim of the present study was to analyze the localization of CD8+ cells in the kidneys of patients with class III and class IV lupus nephritis and to establish correlations with histologic, biologic, and clinical features of SLE. Methods Twenty-five consecutive SLE patients with class III or class IV lupus nephritis were enrolled. Phenotype analyses of blood lymphocytes and renal immunohistochemistry studies were performed. Results CD8+ T cells were the predominant kidney-infiltrating subset of cells. The mean ± SD numbers of CD8+ T cells and CD4+ T cells were 66.2 ± 65.2/mm2 and 19.3 ± 29.4/mm2, respectively. There was a significant correlation between the percentage of blood CD3+,CD8+,DR+ cells and the total number of renal CD8+ T cells (r = 0.42, P = 0.039). Renal CD8+ T cell infiltration correlated well with the renal activity index (r = 0.63, P = 0.0007) and with high serum creatinine levels (r = 0.75, P = 0.0001). This CD8+ T cell infiltrate, which was predominantly in the periglomerular area, was correlated with cellular crescents and Bowman's capsule rupture and was associated with a poor response after conventional induction therapy. Conclusion CD8+ T lymphocytes infiltrate the periglomerular area in patients with severe (class III and class IV) lupus nephritis and are linked to a poor outcome after induction therapy. These results reveal a new potential effector pathway operant in lupus nephritis.