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Introduction Les anticorps anti-nuclear matrix protein 2 (anti-NXP2) sont des auto-anticorps specifiques de myosites initialement identifies dans les dermatomyosites juveniles ou ils sont associes a des atteintes musculaires severes et des calcinoses. Leur expression clinique chez l’adulte est moins connue. Le but de notre etude est de decrire les caracteristiques des patients adultes presentant des anticorps anti-NXP2. Materiel et methodes Etude retrospective du 1er janvier 2017 au 1er juin 2019 incluant les patients de plus de 16 ans avec anticorps anti-NXP2 detectes par un dot myosite au CHU de Caen. Resultats Sur les 112 patients presentant un dot myosite positif, 6 (5 %) avaient des anticorps anti-NXP2. Il s’agissait uniquement de femmes, avec un âge median au diagnostic de 40,5 ans. Le suivi median etait de 21,5 mois. Quatre des 6 patientes presentaient une dermatomyosite avec une atteinte musculaire et cutanee typique de dermatomyosite : signe de la manucure (n = 4), rash peri-orbitaire (n = 3), signe du châle (n = 3), papules de Gottron (n = 2 ; Figure 1 ), syndrome de Raynaud (n = 2), photosensibilite (n = 2) et alopecie (n = 2). Un seul cas de calcinose cutanee etait observe. Une panniculite lobulaire avec adiponecrose et sans vascularite a ete decrite dans un cas ( Figure 2 ). Les atteintes extramusculaires decrites etaient : une atteinte laryngee (1), une myocardite (1), une pneumopathie interstitielle (1), une vascularite digestive (1) et une atteinte articulaire (1). Ces 4 patientes etaient toutes en remission sous traitement immunosuppresseur. Les 2 autres patientes presentaient une myosite de chevauchement definie par la presence d’atteinte musculaire squelettique sans atteinte cutanee et des manifestations extramusculaires au premier plan : troubles de la deglutition (n = 1), dysphonie (n = 1), pneumopathie interstitielle diffuse (n = 2), hypertension arterielle precapillaire (n = 1), vascularite digestive (n = 1) et une atteinte articulaire (n = 1). Ces 2 patientes ont presente une evolution defavorable avec aggravation respiratoire malgre le traitement immunosuppresseur, causant le deces de l’une d’elles. Chez les 6 patientes, aucun cancer n’etait decrit dans les 5 annees precedant ou suivant le debut des symptomes. Discussion Les myosites avec anticorps anti-NXP2 sont rares chez l’adulte et ne presentent pas les memes caracteristiques cliniques que les cas pediatriques. Il s’agit ici soit d’un tableau de dermatomyosite de bon pronostic, sans calcinose ni neoplasie associees. Des atteintes systemiques par vascularite digestive, atteintes ORL ou par pneumopathie interstitielle diffuse, trouvees notamment dans le cadre de myosites de chevauchement, assombrissent le pronostic en l’absence de traitement immunosuppresseur.

BackgroundThe idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases that can affect the muscles, skin, lungs, heart, and joints. Increase knowledge about histopathological findings, clinical manifestations and auto-antibodies have allowed further novel classification of IIMs. Today, the main IMs subgroups are: dermatomyositis (DM), inclusion body myositis (IBM), immune-mediated necrotizing myopathies (IMNM), overlap myositis (OM) and immune-checkpoint inhibitor-related myositis (ICIrm). Axial muscle involvement results either in a “Dropped Head Syndrome (DHS)”, with a marked weakness of the neck extensors, or in a camptocormia (CC), with a weakness of the thoracolumbar paraspinal muscles. This atypical presentation is poorly described in the course of IMs while it may results in a major disability, and may lead to myositis diagnosis delay.ObjectivesThis study aimed to describe IMs revealed by DHS and/or CC. Secondary outcomes were to define subgroups of patients according to clinical, biological and histopathological characteristics. Then, the effects of treatments used were analyzed.MethodsA historical cohort was designed using the register MYOLYON which includes all IMs followed at the University Hospital of Lyon (France) between 2000 and 2021. All patients with IM revealed by DHS and/or CC and having an histologically proven IMs were included, after exclusion of alternative (e.g., myasthenia gravis, motoneuron disease). Clinical, biological, immunological, histopathological data as well as outcome and care were collected through a standardized form. Agreement for the study was obtained from the French Ministry of the Research and the study was approved by the Local Research Ethics Committee.ResultsTwenty-two patients were fully characterized: DM (n=4), IBM (n=7), OM (n=8), ICIrm (n=2) and one myositis with anti-Hu antibodies. Two groups of patients were identified according to the age at first symptoms and to the type of muscle axial involvement (e.g, DHS and/or CC). Before the age of 70 (n=13/22), the two most common diagnoses (n=11/13) were DM (n=4/4) and OM (n=7/8). Axial muscle involvement was diffuse (DHS and CC) in 10/13 patients. After 70 years old (n=9/22), there were a majority of IBM (n=6/9) and all cases of ICIrm (n=2). Axial involvement was restricted to one group of muscles (DHS or CC) in 5/9 patients. Finally, 77% (17/22) of patients had refractory disease and required a second line treatment (e.g, immunoglobulins). All of these results are summarized in the Figure 1.Figure 1.ConclusionWhile IM diagnosis is challenging in the presence of inaugural axial involvement, these results highlight the subset of IM to be considered according to the age at first symptoms and the type of axial involvement (e.g., DHS and/or CC).References[1]Mariampillai, K. et al. Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies. JAMA Neurol75, 1528-1537 (2018).[2]Landon-Cardinal, O. et al. Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies. RMD Open6 (2020).[3]Suarez, G.A. & Kelly, J.J., Jr. The dropped head syndrome. Neurology42, 1625-1627 (1992).[4]Oerlemans, W.G. & de Visser, M. Dropped head syndrome and bent spine syndrome: two separate clinical entities or different manifestations of axial myopathy? J Neurol Neurosurg Psychiatry65, 258-259 (1998).Disclosure of InterestsNone declared

Background: APECED syndrome is a rare monogenic disease caused by homozygous mutation of AIRE gene. It classically presents with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency with an early onset in childhood. Non-endocrine manifestations as ectodermic dystrophy, asplenism and pneumonitis are also observed but their incidence remains unknown and their mechanisms not well understood. APECED has been poorly reported in France although it is widely described in several European countries. The aim of this study was to report on rare manifestations of APECED syndrome in a French cohort. Patients and methods: We performed a multicentric prospective observational study in France in order to collect clinical, biological, immunological and genetic data, after written informed consent in the frame of a PHRC (Hospital Project of Clinical Research #1927). Bronchiolitis, splenic atrophy and ocular manifestations were systematically investigated. Results We enrolled 25 patients between 2009 and 2016. Clinically, the median age at diagnosis was 12 while the median age of the first manifestation was 6, so there was diagnostic delay. The median number of manifestations was seven. 76 % of patients presented with the classical triad. Reduction of lung function was observed in 62% of patients, asplenism in 26%, and ocular manifestation in 33%. Genetically, eleven mutations of the AIRE gene were identified, two of which never previously reported: an intronic variation c.653-70G>A (intron 5) in a patient with hypoparathyroidism as unique manifestation , and c.1066del (p.Arg356GlyfsX22) (exon 9) in a patient from Guadeloupe with composite heterozygous mutations (c.967_979del13; exon 8). The most common AIRE mutation was the mutation R257X. Median age was 26 and sex ratio was 1.1. Biologically, 100% of tested sera were positive for anti-IFNα-antibodies, 15/18 for anti-IL-22, and 13/18 for anti-IL-17F antibodies. Conclusion: This series shows a high genotypic and phenotypic variability of APECED in France, that could be explained by different ethnic origins. The systematic screening for non-classic manifestations shows a more frequent occurrence than in other series. Systematic screening of asplenism and bronchiolitis could be a useful strategy to make an earlier diagnosis, to prevent infections by vaccination and to treat earlier pulmonary involvement. Lastly, antibodies against Th17 cytokines appear as good soluble markers for diagnosis of non-classical presentation of the syndrome.

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children. Its diagnosis is usually made on a clinical basis following the criteria of Bohan and Peter (1975). Recently, the presence of myositis-specific autoantibodies (MSAs) have started to be associated with specific outcome in adult patients; the diagnosis and prognosis value of these autoantibodies remains to be identified in children. We report four cases of JDM with MSAs focusing on clinical, biological, and radiological manifestations, and then we describe associated treatment. The cohort comprises four girls with an average age of 8.5 years. The time to diagnosis was 1 week to 4 months. For these patients, the immunologic study found one patient positive for the MDA5 antibody (or CADM 140), one positive for the TIF1γ antibody (or p155/140), and two patients positive for the NXP2 antibody (or p140/MJ). Each patient showed specific and characteristic cutaneous manifestations. For example, the girl positive for the TIF1γ antibody presented the most severe skin disease with urticaria, face edema, and vascularity of the neck and shoulders. However, regarding muscular features, proximal weakness was present in most of the cohort, except for the child positive for the MDA5 antibody, who presented no sign of muscular disease at the beginning with low CK levels. Importantly, acute pancreatitis also affected this patient. Concerning radiological indications, muscular MRI evidenced hyperinflammation, a sign of diffuse myositis, in all these patients. Treatments consisted in corticosteroids together with methotrexate or mycofenolate mofetil associated or not with intravenous immunoglobulin therapy. This report highlights the importance of systematic detection and analysis of MSA in diagnosis and characterization of JDM, and describes a new approach that would allow more focused treatments and be a useful predictor of clinical complications and prognosis in JDM-affected subjects.

Resume Introduction Les dermatomyosites cliniquement amyopathiques associees aux auto-anticorps anti-MDA5 sont rares et de description tres recente. Observation Une femme de 58 ans a consulte pour dyspnee subaigue de classe IV NYHA, toux, myalgies, arthrites des poignets et scapulalgies, associees a des episodes febriles. L’examen a revele des lesions cutanees de dermatomyosite avec rash, papules de Gottron, « mains de mecanicien » et des râles crepitants a l’auscultation des bases pulmonaires. L’hypoxemie (61 mmHg) etait associee a un trouble ventilatoire restrictif et une diminution de la DLCO. Le scanner thoracique etait compatible avec une pneumopathie organisee. Le lavage broncho-alveolaire montrait 22 % de polynucleaires neutrophiles. La concentration serique de creatine kinase et l’electromyogramme etaient normaux ; la ferritinemie etait elevee. Les auto-anticorps antinucleaires etaient positifs et des auto-anticorps anti-MDA5 ont ete identifies. L’evolution a ete favorable avec la corticotherapie, secondairement associee au mycophenolate mofetil. Conclusion Les dermatomyosites amyopathiques associees aux auto-anticorps anti-MDA5 ont des caracteristiques communes avec celles des dermatomyosites associees aux auto-anticorps anti-synthetases. L’atteinte musculaire est souvent discrete. Le pronostic pourrait etre ameliore par un diagnostic et un traitement plus precoces.

Introduction Les dermatomyosites compliquees de pneumopathies interstitielles rapidement progressives sont rares et sont souvent associees a une categorie specifique d’auto-anticorps des myosites dont font partie les anticorps anti-MDA-5. La presence d’un de ces auto-anticorps est habituellement totalement exclusive. Nous rapportons ici le cas d’une dermatomyosite amyopathique associee a une pneumopathie interstitielle diffuse rapidement progressive, revelee par une alopecie et caracterisee par la presence simultanee d’auto-anticorps anti-MDA-5 et anti-SAE. Observation Une patiente de 63 ans est adressee en consultation de dermatologie pour un bilan d’alopecie centrale non peladique evoluant depuis 5 mois. L’examen physique revele egalement la presence d’un erytheme palmaire bilateral et un erytheme des sourcils. La biopsie du cuir chevelu met en evidence un infiltrat inflammatoire peri-lymphocytaire associee a une discrete dermite de l’interface en surface compatible avec un lupus. Le bilan auto-immun (AAN, ANCA, FR) est negatif et une premiere recherche d’auto-anticorps specifiques des myosites (dont anti-J-O1, EJ, OJ, PL7, PL12, Mi2, Ku, SRP, Scl-70 et anti-PM/Slc) s’avere egalement negative. Parallelement a cette prise en charge, la patiente est hospitalisee pour un tableau de pneumopathie infectieuse liee a l’inhalation de poussieres emanant d’une voliere. Le scanner thoracique met en evidence des lesions de pneumopathie interstitielle bilaterale avec condensation pulmonaires des deux bases compatible avec une psittacose. Une partie des lesions regresse sous antibiotherapie. Une semaine apres la fin de ce traitement, le tableau clinique se complete par l’apparition d’arthromylagies et de troubles de la marche sans deficit moteur. L’electromyogramme est normal et l’IRM des quadriceps ne montre aucun signe de myopathie et aucun signe d’atrophie musculaire. Les CPK et la ferritinemie sont normales. Une corticotherapie est debutee a la posologie d’1 mg/kg/j avec une nette amelioration puis la dyspnee s’aggrave brutalement au palier de 20 mg necessitant un transfert en reanimation. La fibroscopie bronchique et la biopsie pulmonaire n’ont pas pu etre realisees en raison de l’aggravation rapide de l’etat clinique. La recherche d’auto-anticorps « rares » des myosites reviendra finalement positive pour les auto-anticorps anti-MDA-5 et anti-SAE1 (anti-small ubiquitin-like modifier activating enzyme). L’introduction rapide de cyclophosphamide n’a cependant pas reussi a freiner l’evolution defavorable. Conclusion La dermatomyosite associee aux auto-anticorps anti-MDA5 (anti-melanoma differenciation-associated protein 5) reste un challenge diagnostique de part la rapidite et la gravite de l’atteinte pulmonaire mais aussi a cause du polymorphisme des presentations cliniques qui contrastent avec une faible expression musculaire. Les « nouveaux » auto-anticorps ne font pas encore partie du bilan de depistage de premiere intention lors des suspicions des dermatomyosites mais toute presentation clinique atypique doit etre signalee au laboratoire d’immunologie. Dans ces situations, une recherche precoce se reveler etre d’une aide precieuse, notamment lorsque l’atteinte pulmonaire gouverne l’evolution de la maladie. Alors que les myosites de chevauchement, sont connues lors d’association des myosites a d’autres maladies autoimmunes, la presence de plusieurs auto-anticorps specifiques des myosites suggere la possibilite de syndromes de chevauchement au sein meme du groupe des dermatomyosites.

Introduction Le lupus bulleux (LB) est une manifestation rare du lupus systemique (LS), a distinguer d’autres dermatoses bulleuses auto-immunes (DBAI). L’objectif de notre etude etait d’en decrire les aspects cliniques, biologiques, histologiques et therapeutiques a partir d’une serie de 10 cas et d’une revue de la litterature. Materiel et methodes Etaient inclus les cas de LS (criteres ACR ou SLICC 2012), suivis dans 3 centres, ayant une eruption vesiculo-bulleuse, avec histologiquement une bulle sous epidermique et un infiltrat dermique polymorphe ou de polynucleaires neutrophiles (PNN) et exclusion d’une autre DBAI. Une relecture centralisee des histologies et une recherche d’anticorps anti-collagene VII (Ac anti-coll VII) par Elisa et par immunoblot dans les 6 mois precedant ou suivant une poussee de LB etaient realisees. Les cas de la litterature etaient issus d’une recherche Medline entre 01/1980 et 05/2015 avec les memes criteres diagnostiques. Le score Sledai d’activite systemique du LS etait calcule au moment du LB pour tous les cas. Resultats Dix cas etaient inclus et compares aux 106 cas de la litterature. Il s’agissait de femmes (100 % vs. 75 %), de phototype V/VI dans 100 % vs. 33 % des cas, et d’âge median de 24 vs. 27 ans. Les bulles, tendues, survenaient en peau saine (56 % vs. 41 %) et/ou erythemateuse (89 % vs. 75 %), majoritairement sur le tronc, les membres superieurs et le visage, sans photo-exposition exclusive et avec une atteinte muqueuse dans 60 % vs. 50 % des cas. Des plaques urticariennes etaient associees dans 60 % vs. 33 % des cas. L’evolution se faisait sans cicatrice (100 % vs. 84 %) mais avec troubles pigmentaires. Le Sledai median etait de 9 vs. 10 (activite moderee) avec une nephropathie lupique (NL) dans 50 % vs. 39 % des cas. Dans notre serie, l’analyse histologique montrait une bulle sous-epidermique avec un infiltrat riche PNN ou polymorphe du derme superficiel, un alignement des PNN sous la membrane basale (MB), avec leucocytoclasie. L’IFD montrait une fixation lineaire (80 % vs. 71 %) et/ou granuleuse (30 % vs. 36 %) d’IgG (90 % vs. 90 %), IgA (60 % vs. 72 %), IgM (70 % vs. 69 %), et de C3 (90 % vs. 66 %) le long de la MB. L’immunoblot montrait dans 4/7 cas (57 %) un Ac anti-coll VII (bandes 145 et 270 kD), confirme par Elisa dans 3 cas. Au total, 23/32 cas (72 %) de la litterature avaient des Ac anti-coll VII. La dapsone etait constamment efficace (100 % vs. 98 %). En cas d’intolerance ou d’indication systemique, les immunosuppresseurs pouvaient etre efficaces, a l’inverse des corticoides. Discussion Notre serie est conforme aux donnees de la litterature. Le LB s’associe a une activite systemique du LS, avec une NL frequente. L’histologie associe un infiltrat neutrophilique et une leucocytoclasie. L’Ac anti-coll VII est present dans plus de la moitie des cas. La dapsone est le traitement de 1e intention. Conclusion Le LB doit etre plutot considere comme une dermatose bulleuse neutrophilique associee au LS qu’une forme cutanee de lupus.

The French Health Products Safety Agency organized in 2007, for the scheme of the national external quality assessment, a survey on antineutrophil cytoplasmic antibodies (ANCA) including detection and identification of the antibodies. This survey allowed to assess the quality of the different methods of these assays. The detection of ANCA by the indirect immunofluorescence technique was satisfactory. However, the methods of identification gave a high rate of false negative results for the anti-myeloperoxidase antibodies (anti-MPO), especially with the immunodot technique. Concerning the titer of anti-MPO antibodies obtained by ELISA, the broad dispersion of results between reagents pointed out a lack of standardisation of the detection of these antibodies.

Resume Cette revue generale concerne l'ensemble des donnees publiees sur les autoanticorps antirecepteurs et autoanticorps anticanaux transmembranaires. La nature des cibles reconnues par ces autoanticorps, les pathologies associees, leur pouvoir pathogene et les principales techniques de detection utilisees pour les mettre en evidence, sont presentes. Parmi les autoanticorps decrits, certains sont directement impliques dans la pathogenie des maladies auto-immunes, pour d'autres leur role pathogene n'est pas certain. Meme si l'intervention de ces autoanticorps dans le developpement des maladies auto-immunes est limitee, leur presence est importante sur le plan du diagnostic avec des marqueurs tres specifiques de certaines pathologies ; ainsi, certains autoanticorps sont recherches en pratique courante comme les autoanticorps antirecepteurs de l'acetylcholine (RACh), les autoanticorps anticanaux calciques et potassiques ; d'autres autoanticorps ne sont recherches que ponctuellement et uniquement par des laboratoires specialises. Cette revue sera divisee en trois parties nous permettant de decrire l'ensemble des principaux autoanticorps antirecepteurs et anticanaux decrits ; cette liste n'est cependant pas exhaustive. La famille des autoanticorps antirecepteurs membranaires dont les autoanticorps antirecepteurs a activite enzymatique (souvent tyrosine kinase) associee ou intrinseque avec un seul domaine transmembranaire, les autoanticorps antirecepteurs lies aux proteines G avec sept domaines transmembranaires, les autoanticorps anticanaux ioniques et les autoanticorps antirecepteurs lies a la membrane par le glycosyl phosphatidyl inositol puis la famille des autoanticorps antirecepteurs intracellulaires dont les autoanticorps antirecepteurs des estrogenes, les autoanticorps antirecepteurs des androgenes, les autoanticorps antirecepteurs de la lamine et les autoanticorps antirecepteurs de la kinesine seront decrits.

This review of literature concerns the different autoantibodies directed against membrane receptors and ion channels. The target antigens, the associated pathologies, the pathogenesis and the methods of detection of these autoantibodies will be addressed. Some of these autoantibodies are thought to be closely related to the autoimmune disease whereas for some others their pathogenesis role is still unclear. Overall, the roles of antibodies are different between diseases, but the presence of such autoantibodies support the basis of intervening immunotherapy, antibody titers predicted the activity of the diseases and some of them are very specific and become the useful markers for the diagnosis. Some autoantibodies are detected routinely as the antiacetylcholine receptor, voltage-gated potassium and calcium channels autoantibodies whereas most of them are detected very rarely and only by specialized laboratories. This review will be divided in three parts with the following classification: the first group of autoantibodies directed against membrane receptors included receptors with an enzymatic activity (mostly tyrosine kinase) with one transmembrane domain, receptors associated to G protein with seven transmembrane domains, ion channels and receptors associated to the membrane by the glycosyl phosphatidyl inositol and the second group of intracellular receptor autoantibodies directed to the estrogens, androgens, lamin and kinesin receptors.

Resume Cette revue generale concerne l'ensemble des donnees publiees sur les autoanticorps antirecepteurs et autoanticorps anticanaux transmembranaires. La nature des cibles reconnues par ces autoanticorps, les pathologies associees, leur pouvoir pathogene et les principales techniques de detection utilisees pour les mettre en evidence sont presentees. Parmi les autoanticorps decrits, certains sont directement impliques dans la pathogenie des maladies auto-immunes, pour d'autres, leur role pathogene n'est pas certain. Meme si l'intervention de ces autoanticorps dans le developpement des maladies auto-immunes est limitee, leur presence est importante sur le plan du diagnostic avec des marqueurs tres specifiques de certaines pathologies ; ainsi, certains autoanticorps sont recherches en pratique courante comme les autoanticorps antirecepteurs de l'acetylcholine (RACh), les autoanticorps anticanaux calciques et potassiques ; d'autres autoanticorps ne sont recherches que ponctuellement et uniquement par des laboratoires specialises. Cette revue sera divisee en trois parties, nous permettant de decrire l'ensemble des principaux autoanticorps antirecepteurs et anticanaux decrits ; cette liste n'est cependant pas exhaustive. La famille des autoanticorps antirecepteurs membranaires dont les autoanticorps antirecepteurs a activite enzymatique (souvent tyrosine kinase) associee ou intrinseque avec un seul domaine transmembranaire, les autoanticorps antirecepteurs lies aux proteines G avec sept domaines transmembranaires, les autoanticorps anticanaux ioniques et les autoanticorps antirecepteurs lies a la membrane par le glycosylphosphatidylinositol puis la famille des autoanticorps antirecepteurs intracellulaires dont les autoanticorps antirecepteurs des estrogenes, les autoanticorps antirecepteurs des androgenes, les autoanticorps antirecepteurs de la lamine et les autoanticorps antirecepteurs de la kinesine seront decrits.

Resume But. – Le but de notre travail est de determiner et comparer la sensibilite des techniques Elisa, dot blot et immunotransfert pour la recherche des anticorps antihistones d'isotype IgG dans une population de lupus erythemateux systemique. La correlation entre les anticorps antihistones et les principaux signes cliniques du lupus erythemateux systemique d'une part et les anticorps anti-ADNnatif d'autre part est egalement etudiee. Materiel et methodes. – Cent vingt-six serums, preleves chez des patients ayant au minimum quatre criteres de l'American college of rheumatology pour le diagnostic du lupus erythemateux systemique, sont testes par les techniques Elisa et dot blot pour la recherche des anticorps antihistones diriges contre l'ensemble des histones. Quatre-vingt-huit serums parmi les 126 sont testes par immunotransfert pour identifier les differentes classes d'histones cibles des anticorps : H1, H2A, H2B, H3 et H4. Cinquante serums preleves chez des donneurs de sang ont servi de temoins negatifs. Resultats. – La sensibilite des anticorps antihistones recherches par les techniques dot blot et Elisa est de 69 et 54 % respectivement plus faible que celle des les anticorps anti-ADNnatif (83 %). La sensibilite de la technique d'immunotransfert pour la recherche des anticorps antihistones est de 72 %. La frequence des anticorps antihistones de classe H1, de classe H2A, de classe H2B, de classe H3 et de classe H4 est de 60, 53, 48, 36 et 29,5 % respectivement. Il existe une correlation entre les anticorps anti-ADNnatif et les anticorps antihistones recherches par les techniques dot blot et Elisa. Les anticorps antihistones recherches par la technique Elisa sont correles avec l'atteinte renale au cours du lupus erythemateux systemique et ont une specificite et des valeurs predictives positive et negative pour l'atteinte renale superieures a celles des les anticorps anti-ADNnatif. Conclusion. – La technique de dot blot a une meilleure sensibilite que la technique Elisa mais cette derniere a permis de depister des cas negatifs en dot blot. Les anticorps antihistones recherches par la technique Elisa ont un caractere predictif pour l'atteinte renale plus important que celui des anticorps anti-ADNnatif. Les anticorps antihistones diriges contre l'histone H1 sont predominants au cours du lupus erythemateux systemique et sont fortement correles avec les anticorps anti-ADNnatif et l'atteinte renale.

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children. Its diagnosis is usually made on a clinical basis following the criteria of Bohan and Peter (1975). Recently, the presence of myositis-specific autoantibodies (MSAs) have started to be associated with specific outcome in adult patients; the diagnosis and prognosis value of these autoantibodies remains to be identified in children. We report four cases of JDM with MSAs focusing on clinical, biological, and radiological manifestations, and then we describe associated treatment. The cohort comprises four girls with an average age of 8.5 years. The time to diagnosis was 1 week to 4 months. For these patients, the immunologic study found one patient positive for the MDA5 antibody (or CADM 140), one positive for the TIF1γ antibody (or p155/140), and two patients positive for the NXP2 antibody (or p140/MJ). Each patient showed specific and characteristic cutaneous manifestations. For example, the girl positive for the TIF1γ antibody presented the most severe skin disease with urticaria, face edema, and vascularity of the neck and shoulders. However, regarding muscular features, proximal weakness was present in most of the cohort, except for the child positive for the MDA5 antibody, who presented no sign of muscular disease at the beginning with low CK levels. Importantly, acute pancreatitis also affected this patient. Concerning radiological indications, muscular MRI evidenced hyperinflammation, a sign of diffuse myositis, in all these patients. Treatments consisted in corticosteroids together with methotrexate or mycofenolate mofetil associated or not with intravenous immunoglobulin therapy. This report highlights the importance of systematic detection and analysis of MSA in diagnosis and characterization of JDM, and describes a new approach that would allow more focused treatments and be a useful predictor of clinical complications and prognosis in JDM-affected subjects.

A 53-year-old man with a history of bilateral cataract surgery at the age of 32 years with ‘a negative work-up’ and no family history was referred for fatigue, intermittent fever, night sweats and cough for the last 2 months. At examination, he appeared fatigued and febrile (38.6°C). He also complained with perioral and limb paresthesiae, and muscles cramps of recent onset. Trousseau and Chvostek signs were both present. Blood cell count showed a hemoglobin level of 8.6 g/dl with a mean corpuscular volume of 73 fl and 54 000 reticulocytes/mm3, a white blood cell count of 6100/mm3 with 73% neutrophils and 15% lymphocytes and the platelet count was 363 000/mm3. Immunophenotyping of lymphoid cells showed 738 CD4+ cell/mm3 and 276 CD8+ cell/mm3 and a normal level at 9% of CD25+ CD127 low/reg of CD4 cell count. Human immunodeficiency virus testing was negative. Serum creatinine and liver function tests were normal, serum albumin was 32.8 g/l (normal 39–46 g/l). Serum total calcium level was 1.07 mmol/l (normal 2.16–2.52 mmol/l) and phosphate level 1.44 mmol/l (normal 0.85–1.31 mmol/l). A further evaluation of calcium homeostasis was performed showing: serum ionized calcium …

Le syndrome autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) est une entite rare, autosomique recessive, qu’authentifie la genetique moleculaire. En raison de son extreme gravite et du risque d’atteintes viscerales letales, il est a distinguer rapidement des autres polyendocrinopathies auto-immunes. But de l’etude Independamment du type d’atteinte clinique, evaluer la valeur diagnostique des auto-anticorps (AC) anti-interferon de type 1, anti-NALP5, et anti-cytokines de type Th17, decrits anterieurement dans l’APECED. Methodes Vingt-trois patients APECED issus de la cohorte correspondant a l’enquete prospective nationale ont ete etudies pour les AC anti-cytokine (Elisa) et NALP5 (radioligand binding assay), comparativement a un groupe temoin de 23 patients atteints d’autres endocrinopathies auto-immunes. Resultats Les AC anti-INF α2A sont observes chez tous les APECED et 21 % des temoins, les anti-INFω chez 56 % des APECED et 4 % des temoins, les anti-INFλ chez 35 % des APECED et aucun temoin. Les anti-IL22 sont mis en evidence chez 78 % des APECED et 9 % des temoins, les AC anti-IL17A chez 9 % des APECED et des temoins, les AC anti-IL17F chez 70 % des APECED et aucun temoin, les AC anti-NALP5 chez 30 % des APECED et aucun temoin. Conclusion Les AC anti-INF de type 1, les anti-IL17F et les AC anti-NALP5 apparaissent les plus specifiques du syndrome APECED. Lorsque la disponibilite technique l’autorisera, l’evaluation d’un panel d’AC chez un patient d’atteint d’endocrinopathie auto-immune particuliere, pourrait constituer une alternative diagnostique simple et rapide a l’evaluation genetique, voire contribuer a elargir la reconnaissance de l’affection.

Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies is a rare and very recently described clinical entity.A 58-year-old woman was admitted with subacute onset of dyspnea (NYHA class IV) associated with cough, oligoarthritis of the wrists, myalgia and intermittent fever. Examination demonstrated skin lesions with heliotrope rash, Gottron's papules, "mechanics hands", and basal inspiratory crackles on lung auscultation. Pulmonary function tests showed a restrictive ventilatory defect, with decreased carbon monoxide diffusion capacity and marked hypoxemia (PaO2 61 mmHg). The chest high-resolution computed tomography appearances were consistent with organizing pneumonia. Bronchoalveolar lavage differential cell count demonstrated 22 % neutrophils. Serum creatine kinase and electromyography were normal ; the serum ferritin level was elevated. Antinuclear antibodies were present and anti-MDA5 autoantibodies were identified. Significant improvement was obtained with systemic corticosteroids, later converted to mycophenolate mofetil as a steroid-sparing agent.Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies shares some characteristics with those associated with anti-synthetase antibodies. Muscular involvement may be mild or absent. Early diagnosis and treatment may improve outcome.

Objectif Le transporteur de zinc ZnT8 est un antigene majeur des cellules beta. Des etudes ont montre que les anticorps (Ac) anti-ZnT8 ameliorent la sensibilite de detection des sujets diabetiques de type 1 (DT1) et des sujets avec un DT1 lent (LADA) en addition aux autres anticorps specifiques des ilots de Langerhans. L’objectif etait d’etudier l’apport diagnostique des Ac anti-ZNT8 dans une cohorte de « vraie vie » pediatrique et adulte. Materiel et methodes Cette etude retrospective a inclus 516 patients (215 enfants et 301 adultes) pour lesquels un dosage des Ac anti-GAD, anti-IA2 et anti-ZnT8 a ete realise. Les Ac anti-GAD et anti-ZnT8 ont ete testes par Elisa (Medizym®, Medipan), les anti-IA2 ont ete testes par Elisa (Medizym®, Medipan) ou par dosage radio-immunologique (Cisbiointernational). Resultats Parmi les 228 patients presentant un diabete auto-immun, les prevalences des Ac anti-GAD, anti-IA2 et anti-ZnT8 etaient respectivement de 64 %, 33 % et 48 %. 73 % des patients presentaient des Ac anti-GAD et/ou anti-IA2 positifs. En ajoutant les Ac anti-ZnT8, 81 % avaient au moins un Ac positif (augmentation de la sensibilite de detection de 8 %). Chez les patients testes a la decouverte du diabete auto-immun (n = 120, âge moyen : 11,36 ans), les Ac anti-ZnT8 etaient positifs chez 68 % des sujets et positifs de maniere isolee chez 7 % des sujets. Conclusion Les Ac anti-ZnT8 augmentent la sensibilite de detection des sujets DT1 ou LADA en addition aux Ac anti-GAD et anti-IA2, et le couple Ac anti-GAD/anti-ZnT8 semble plus performant que le couple Ac anti-GAD/anti-IA2 pour detecter les diabetes auto-immuns.

We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis.

We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis.

The RET proto-oncogene has been demonstrated to be expressed in medullary thyroid carcinomas and pheochromocytomas, and was mutated in patients with the multiple endocrine neoplasia type 2A (MEN 2A). The results presented herein show its expression in normal human thyroid parafollicular C cells. Since RET is predicted to encode a receptor for a still unknown ligand, these data confirm its involvement in the regulation and growth of these cells.

Non-thyroid neoplasia were analysed by Southern blot of genomic DNA and DNA prepared by reverse transcription and amplification by polymerase chain reaction (RT/PCR) for the activation of the RET oncogene. It is known that the rearrangement of RET occurs in about 10%-20% of human thyroid papillary carcinomas. None of 528 non-thyroid tumours showed rearrangement of the RET proto-oncogene, whereas three out of 30 thyroid papillary carcinomas were positive for RET activation. Therefore the activation of RET seems to be a somatic cell mutation specific to human thyroid carcinomas. © 1993, Macmillan Press Ltd.

Esophageal involvement occurs in about 80% of patients with systemic sclerosis, with a marked diminution of peristaltic pressures in the distal two-thirds of the esophagus. Our aims were to more fully characterize esophageal motility disorders in systemic sclerosis using high-resolution manometry (HRM) and to determine predictive factors of esophageal involvement. Fifty-one patients (46 females) with systemic sclerosis were included in this retrospective study. Esophageal motility was characterized with HRM. The demographic data, esophageal symptoms, presence of other organ involvement, and autoantibody profile (anti-Scl70 antibodies [Scl70], anticentromere antibodies [ACA]) were recorded for all patients. Esophageal body dysmotility was present in 33 patients (67.3%) and was associated with hypotensive esophagogastric junction in 27 patients (55.1%). The velocity of proximal contractions was higher in patients with esophageal body dysmotility compared to patients with normal peristalsis (median 10.8 cm/s vs. 5.5, P = 0.04). The amplitude of middle esophageal contraction but not of distal esophageal contraction was reduced in patients with hypoperistalsis. Diffuse esophageal skin involvement, presence of Scl70 and absence of ACA were associated with esophageal involvement. Esophageal symptoms encountered in 87.5% of patients were not predictive of esophageal dysmotility. This HRM series confirms the high prevalence of esophageal body dysmotility in systemic sclerosis. Diffuse skin involvement, positive Scl70 and negative ACA, but not esophageal symptoms, may predict esophageal body dysmotility.

The association of positive cytoplasmic antineutrophil antibody (ANCA) necrotizing crescentic glomerulonephritis with endocarditis raises diagnostic issues. Indeed, it is often difficult to determine if the kidney injury is either secondary to an infectious disease or caused by an ANCA-associated small vessel vasculitis. We report a 59-year-old man admitted in nephrology for acute glomerular syndrome in whom the renal biopsy showed a crescentic necrotizing glomerulonephritis. A diagnosis of vasculitis was initially considered in the presence of high titer of ANCA (anti-proteinase 3). Because of associated Staphyloccocus aureus endocarditis the patient received both corticosteroids and antibiotics that allowed remission of both kidney injury and endocarditis. The renal presentation and the disappearance of ANCA support the infectious etiology of this glomerulonephritis rather than an ANCA-associated small vessel vasculitis. It is important to be cautious in the presence of ANCA positive extracapillary glomerulonephritis and endocarditis should be ruled out before initiation of corticosteroids that may be nevertheless necessary in severe acute glomerulonephritis.

Thrombotic events may occur in celiac disease. In this study, we analyzed clinical features and risk factors for thrombosis in seven patients who had celiac disease and thrombosis.We retrospectively studied 87 patients with adult celiac disease and identified seven cases of thrombosis. We searched if risk factors for thrombosis were identified and tested retrospectively antiphospholipid antibodies on the serum.In our study, the global prevalence of thrombosis was 8 %, and 5.7 % for spontaneous thrombosis, with venous thrombosis (n=5) or arterial thrombosis (n=1) or both (n=2). The seven patients consisted in six women and one man with a mean age of 44.8 years at time of thrombosis. Thrombotic events occurred before the diagnosis of celiac disease in four cases. In three cases, venous thrombosis was in unusual sites: portal (n=2), splenic vein thrombosis (n=1). In six cases, we identified risk factors for thrombosis, which could be linked to celiac disease: hyperhomocysteinemia (n=1), protein C and S deficiency due to vitamin K deficiency (n=3) and antiphospholipid antibodies (n=2).Such risk factors for thrombosis should be identified in patients in adult celiac disease in order to correct them and add a thromboembolic prophylaxis.

The aim of this study was to determine the prevalence of different auto-antibodies in adult, French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. The sera of 144 patients were screened for a wide range of antibodies. Clinical, biological and bacteriological characteristics and the cystic fibrosis transmembrane conductance regulator genotype were recorded and progression of lung disease was examined. 113 (78.5%) patients displayed one or several auto-antibodies, predominantly immunoglobulin (Ig)A anti- Saccharomyces cerevisiae antibodies (ASCA; 43.7%) and antineutrophil cytoplasmic antibodies (ANCA; 40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, Pseudomonas aeruginosa colonisation, the presence of resistant P. aeruginosa , low forced expiratory volume in 1 s, CF-related liver disease, hypergammaglobulinaemia, male sex and inflammatory syndrome. The presence of ASCA-IgA was correlated with male sex and hypergammaglobulinaemia. 41 patients presented with chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA-IgA. These findings confirm the high frequency of auto-antibodies in CF, particularly BPI-ANCA and ASCA-IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.

To the Editors: Whereas tobacco smoking is a well-established risk factor for the development and progression of chronic obstructive pulmonary disease (COPD), the molecular basis for individual predisposition and disease progression remains largely unknown. Immunological processes and especially autoreactive immune processes have recently been implicated, with anti-elastin antibodies and a T-helper type-1 lymphocyte response identified in patients with COPD/emphysema 1. Immune mechanisms are also implicated in interstitial lung disease and pulmonary fibrosis 2, and smoking-induced autoimmunity has been demonstrated in rheumatoid arthritis 3. We explored whether an autoimmune process implicating anti-elastin autoantibodies and facilitated by tobacco smoking may take place in patients with combined pulmonary fibrosis and emphysema (CPFE), a distinct entity recently defined on the basis of characteristic features of chest imaging, pulmonary function and outcome 4. Patients with CPFE, diagnosed within …

Any dense cytoplasmic fluorescence on Hep-2000 cells seen in the immunology laboratory of the Clermont-Ferrand teaching hospital was closely studied to determine the presence or not of anti-PL antibodies.From January 2006 to January 2007, twelve patients presented a dense cytoplasmic fluorescence on Hep-2000 cells. So we activated a Hep-2 cells'slide, a triple substrate's slide and a dot in order to exclude antiribosomes and anti-JO1 antibodies. After having excluded these antibodies, we sent the sera to the immunology laboratory of the South Lyon hospital to confirm the dense cytoplasmic fluorescence and to detect anti-PL antibodies.Four patients presented anti-PL7 and three anti-PL12. For four other patients, the dense cytoplasmic fluorescence was only due to anti-SSA antibodies. Last for one patient, no antibody was found despite an evocative clinic of myositis.The systematically extensive exploration during the discovery of a dense cytoplasmic fluorescence proved very efficient, permitting to diagnose five new cases of antisynthetases syndrome including three not evoked by the clinician and to confirm two cases clinically known. This study permitted us to better recognize anti-PL from others dense cytoplasmic fluorescences and not to mix them up with particular anti-SSA.

Aims The objective of our study was, in one hand, to determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ELISA and dot blot assay to investigate IgG M2 antimitochondrial antibodies (M2 AMA) and, on the other hand, to compare these results with those of indirect immunofluorescence technique (IIF). Methods Sera from patients suffering from primary biliary cirrhosis (PBC) (n = 55), systemic lupus erythematosus (n = 21), celiac disease (n = 30) and blood donors (n = 75) were analyzed. M2 AMA were detected by ELISA and dot blot using pyruvate dehydrogenase purified from porcine heart and by IIF on cryostat sections of rat liver-kidney-stomach. Results IIF was more sensitive (98%) than ELISA (93%) and dot blot (91%). The specificity of AMA for PBC using IIF, ELISA and dot blot reached 100%, 92% and 100%, respectively. The PPV of IIF, ELISA and dot blot was 100%, 93% and 100%, respectively. The NPV was 98% for IIF, 92% for ELISA and 91% for dot blot. Conclusion Dot blot, using purified pyruvate dehydrogenase, had a higher specificity than ELISA and may be useful in confirming the specificity of AMA in cases of doubt with IIF.

Background Lupus nephritis (LN) frequently occurs in the clinical course of childhood-onset systemic lupus erythematosus (cSLE) and is involved in higher long-term morbidity and mortality of the disease compared to adults. Avoiding a progression to end-stage renal disease and, in the same time, minimizing current toxic treatment regimens is challenging in such young patients. Hence, clinicians need reliable biological markers in order to predict renal involvement. The association of anti-C1q antibodies (Abs) with lupus nephritis in adults is supported by several studies but remains uncertain in children. Objectives This single center study aimed at investigating the capacity of anti-C1q Abs to predict renal flare at diagnosis and during the follow-up of cSLE. Methods Anti-C1q Abs assays were performed retrospectively by ELISA in 17 patients from a single tertiary center, presenting with cSLE at diagnosis, at time of a renal flare-up or in a quiescent phase of the disease. Disease activity was measured with SLEDAI score which includes dsDNA aAbs. C3, C4, type I interferon were also analyzed in all patients. Results Five patients with a renal involvement at diagnosis of cSLE had positive anti-C1q aAbs at a high rate (>200UI/ml) (100%). A total of 11 flares were recorded during the time of the study. Anti-C1q antibodies were positive in 8 of these flares (72,7%). The negativity of anti-C1q Abs during these flares (n=3) was presumably due for one patient to a monogenic form of cSLE associated with a homozygous PRKCD mutation. In the other cases, levels of anti-C1q Abs were just below the limit of positivity and became positive at the time of the next renal flare. Conclusions Anti-C1q antibodies represent a reliable marker of LN flares in children with cSLE and may be performed routinely during the follow-up of these patients. References Orbai, A.-M. et al. Anti-C1q antibodies in systemic lupus erythematosus. Lupus 24, 42–49 (2015). Yin, Y., Wu, X., Shan, G. & Zhang, X. Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis. Lupus 21, 1088–1097 (2012). Gilliam, B. E., Ombrello, A. K., Burlingame, R. W., Pepmueller, P. H. & Moore, T. L. Measurement of autoantibodies in pediatric-onset systemic lupus erythematosus and their relationship with disease-associated manifestations. Semin. Arthritis Rheum. 41, 840–848 (2012). Wu, F. Q., Zhao, Q., Cui, X. D. & Zhang, W. C1q and anti-C1q antibody levels are correlated with disease severity in Chinese pediatric systemic lupus erythematosus. Rheumatol. Int. 31, 501–505 (2011). Edelbauer, M. et al. Markers of childhood lupus nephritis indicating disease activity. Pediatr. Nephrol. 26, 401–410 (2011). Disclosure of Interest None declared

The B-CPAP cell line was obtained from a human differentiated papillary thyroid carcinoma. Previous studies showed that the cells present thyroid characteristics such as thyroglobulin production, phenotypic alterations such as synthesis of human chorionic gonadotropin hormone (HCG), expression of neuron specific enolase (NSE) and protein S100, and also somatic mutations of p53 and K-rns oncogenes. The present data further characterize this cell line and show an overexpression of transforming growth factor (TGF beta 1) and c-met gene product i.e. the receptor for human growth factor (HGF). The relation between the phenotypic and somatic alterations in the process of malignancy are discussed.

This review of literature concerns the different autoantibodies directed against membrane receptors and ion channels. The target antigens, the associated pathologies, the pathogenesis and the methods of detection of these autoantibodies will be addressed. Some of these autoantibodies are thought to be closely related to the autoimmune disease whereas for some others their pathogenesis role is still unclear. Overall, the roles of antibodies are different between diseases, but the presence of such autoantibodies support the basis of intervening immunotherapy, antibody titers predicted the activity of the diseases and some of them are very specific and become the useful markers for the diagnosis. Some autoantibodies are detected routinely as the antiacetylcholine receptor, voltage-gated potassium and calcium channels autoantibodies whereas most of them are detected very rarely and only by specialized laboratories. This review will be divided in three parts with the following classification: the first group of autoantibodies directed against membrane receptors included receptors with an enzymatic activity (mostly tyrosine kinase) with one transmembrane domain, receptors associated to G protein with seven transmembrane domains, ion channels and receptors associated to the membrane by the glycosyl phosphatidyl inositol and the second group of intracellular receptor autoantibodies directed to the estrogens, androgens, lamin and kinesin receptors.

Aims. – The purpose of our study is to determine the sensitivity, specificity and predictive values of an enzyme linked immunosorbent assay (ELISA) and a dot blot assay for the detection of IgA class anti-tissue transglutaminase antibodies (IgA-AtTGA) and to compare these results with those of IgA class anti-endomysium antibodies (IgA-AEA), IgA class anti-reticulin antibodies (IgA-ARA) and IgA class anti-gliadin antibodies (IgA-AGA). Patients. – Serum samples from 143 patients (97 children, 46 adults) with untreated celiac disease (CD) confirmed by intestinal biopsy and 74 disease controls (64 children, 10 adults) were studied. Methods. – The anti-tissue transglutaminase antibodies were detected by dot blot assay and an ELISA using guinea pig tissue transglutaminase (gp-tTG) as antigen. The anti-endomysium antibodies were detected by an indirect immunofluorescence technique on cryostat sections of human umbilical cord. The anti-reticulin antibodies were also investigated by indirect immunofluorescence on cryostat sections of kidney, liver and stomach of rat. The anti-gliadin antibodies were determined by an ELISA. Results. – The sensitivity of an ELISA for the detection of anti-tissue transglutaminase antibodies was 86% in children and 87% in adults and the sensitivity of dot blot assay was 57% in children and 54% in adults. The specificity of an ELISA and dot blot for the detection for anti-tissue transglutaminase antibodies was, respectively, 96% and 88% lower than that of anti-endomysium antibodies (100%). The sensitivity of anti-gliadin antibodies was 97% in children and 91% in adults and their specificity was 85%. The sensitivity of anti-reticulin antibodies was 94% in children and 87% in adults. Their specificity was 100%. Conclusions. – The sensitivity and specificity of an ELISA for the detection of anti-tissue transglutaminase antibodies were better than that of dot blot assay. However, this dot blot assay could screen four celiac patients who have not had anti-tissue transglutaminase antibodies by an ELISA. The sensitivity of anti-endomysium antibodies was better than that of anti-tissue transglutaminase antibodies, anti-reticulin antibodies and anti-gliadin antibodies but in children aged less than 2 years, the sensitivity of anti-gliadin antibodies was better than that of anti-tissue transglutaminase antibodies.

Thymomas are thymic tumors composed of epithelial cells with various number of lymphocytes. On the basis of lymphocytes number, they can be histologically classified into predominantly lymphocytic, predominantly epithelial and mixed lympho-epithelial. These tumors are rare and their prognosis is not well known yet. In this study we demonstrate by in situ hybridization the presence of RET transcripts in the medullary part of normal murine thymus and in epithelial thymomas. Conversely RET expression was not detected in the cortical part of the thymus and in thymomas with the predominance of the lymphocytic component, suggesting that its expression could be a specific marker of the predominantly epithelial histotype.

The purpose of our study is to determine and compare the sensitivity of an enzyme linked immunosorbent assay (ELISA), a dot blot assay and an immunoblot assay for the detection of the IgG class antihistones antibodies in a population of systemic lupus erythematosus. The correlation between antihistones antibodies and the main clinical features of SLE or between antihistones antibodies and the presence of anti-double-stranded-DNA antibodies were analysed.Serum samples from 126 systemic lupus erythematosus patients, classified according to the criteria of the American College of Rheumatology, were analysed for the presence of antihistones antibodies using a dot blot assay and an ELISA. Antihistones subfractions antibodies were assessed using the immunoblot technique on 88 out of the 126 sera. Serum samples from 50 blood-donors were analyzed as negative controls.The sensitivity of antihistones antibodies assessed by dot blot assay and ELISA was 69% and 54% respectively, and was lower than that of anti-double-stranded-DNA antibodies (83%). The sensitivity of the immunoblot assay for the detection of antihistones antibodies was 72%. Incidence of autoantibodies against histones H1, H2 A, H2B, H3 and H4 was 60%, 53%, 48%, 36% and 29.5% respectively. We found a correlation between the presence of antihistones antibodies, detected by the dot blot assay and ELISA, and the presence of anti-double-stranded-DNA antibodies. Antihistones antibodies detected by ELISA were correlated with renal disease in systemic lupus erythematosus; they showed a specificity, a positive and a negative predictive value for renal disease in systemic lupus erythematosus higher than those of anti-double-stranded-DNA antibodies.The sensitivity of the dot blot assay for the detection of antihistones antibodies is better than that of ELISA, but the latter technique could detect some cases negative by ELISA. Antihistones antibodies detected by ELISA have an important predictive value in the renal complications in systemic lupus erythematosus, better than that of AdsDNA. Antibodies to histone H1 were the most frequent antihistones autoandibodies in systemic lupus erythematosus and they were highly correlated with anti-double-stranded-DNA antibodies and renal disease.

Objective: To assess the implication of hepatitis C virus (HCV) infection in the development of autoimmune thyroid response, thyroid autoantibodies were studied in serum of HCV positive patients. Methods: Anti-microsomal, anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin antibodies were evaluated in the sera of 100 patients with chronic hepatitis C (53 women and 47 men; mean age = 55#x00B1;5 years). In parallel, thyroid autoantibodies were investigated in blood samples obtained from two separated control groups: age-matched HCV negative-HBV positive patients (25 women, 25 men; mean age= 47#x00B1;6 years) and healthy blood donors (29 women and 21 men; mean age= 54#x00B1;8 years). Results: Anti-thyroid antibodies were found more frequently in HCV positive women when compared to the men (8/53= 15.1#x0025; vs 0/47= 0#x0025;,.p0.01).The prevalence of these autoantibodies was not statistically different between HCV positive and healthy female blood donors. However the investigation of thyroid autoantibody titers showed significantly higher levels of anti-TPO and anti-microsomal antibodies in HCV positive women in comparison with healthy women controls (respectively 1: 83200 vs 1: 1900 and 834 vs 23, p0,01). Conclusions: This strong association between HCV infection and high levels of anti-thyroid autoantibodies in women outlines the interest of systematic detection of anti-microsomal and/or anti-TPO antibodies in this population.

This retrospective study was performed to evaluate the interest of cytology in the diagnosis of pulmonary carcinomas. Bronchial samples were collected from 330 patients known to display a macroscopic lesion which was detected by bronchoscopy. Cytological analysis of the bronchial brushings and washings, removed at the first fibroscopy, allowed the diagnosis of malignancy in 92% of the cases analyzed whereas the biopsy confirmed the malignancy in 77% of the cases. In conclusion cytological studies gave information on malignity and classification in 90% of the cases. However histological classification only could guarantee the choice of the best treatment regimen.

To compare the protective effects of IGF-1 and insulin on the autoimmune process of beta-cell destruction, permissive NOD recipients were adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and then administered either 10 micrograms of rhIGF-1 or 0.5 unit of regular insulin subcutaneously twice daily for three weeks. The final incidence of successful transfers of diabetes observed at day 22 was significantly reduced in 1/12 mice (8.3%) treated with IGF-1, while diabetes was observed in 4/10 (40%) receiving insulin and 7/11 (63.4%) controls. A marked reduction of insulitis during histological analysis of the pancreatic glands of IGF-1 or insulin-treated mice was also observed. Non-diabetic mice treated with rhIGF-1 had a higher mean +/- SD percentage of intact islets (68.9 +/- 36% vs 10.7 +/- 13%, p0.01) and a lower percentage of severely infiltrated islets (5.7 +/- 9.8% vs 30.3 +/- 21%) than non-diabetic control mice. Insulin reduced islet-cell infiltration, though to a lesser extent, with a high percentage of normal islets (55.2 +/- 31%, p0.02). Some mice developed diabetes and severe islet-cell infiltration despite rhIGF-1 or insulin, thus indicating that some committed T cells were still able to invade islets and cause beta-cell destruction. To evaluate the effects of rhIGF-1 and insulin on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1, 2 mice injected into congenic NOD-N Thy-1, 1 mice were monitored three weeks after adoptive cell transfer. The percentage of Thyq-1.2+ T cells was significantly reduced in the spleen (10.8 +/- 1.3% vs 17.2 +/- 3.9%, p = 0.004) of rhIGF-1 treated mice as compared to the thymus (68.4 +/- 7.9% vs 72.87 +/0 6.2, p = 0.306). Similar experiments performed in mice treated with insulin revealed no significant differences in the percentages of Thy-1,2+ T cells compared to controls in the spleen (l4.3 +/- 1.4%), thymus (84 +/- 2.5%) or pancreatic lymph nodes (21.5 +/- 1.6% vs 23.4 +/- 1.5%) of treated animals. These results suggest that rhIGF-1, as compared to insulin, could influence T-cell trafficking to the lymphoid organs in addition to affecting beta cells. These findings may have important implications for new preventive strategies in human Type 1 diabetes mellitus.

One of the difficulties in characterization of the oncogenes involved in thyroid carcinogenesis is the production of cell lines. Arising from a poorly differentiated thyroid papillary carcinoma we have established a cell line synthesizing the thyroglobulin and human chorionic gonadotropin (alpha and beta subunits) (HCG) hormones. These cells will allow research of the oncogenes involved or potentially involved in thyroid papillary carcinomas and evaluation of the role of the autocrine secretion of HCG.

Different hormones (thymulin, thymosin alpha 1, vasopressin), antigenic markers of cortical and subcapsular/medullary thymic areas and tumour associated antigens were studied on paraffin or frozen section and cultures of human epithelial thymic tumours ('thymomas'). Thymulin, thymosin alpha 1 and for the first time vasopressin are found in most tumours. The epithelial cells of five 'thymomas' had markers of both cortical (TE3) and subcapsular/medullary thymic regions (A2B5 and/or TE4 and/or anti-p19). Leu-7, a marker of subcapsular epithelial cells was positive only in two tumours. The histological classification into cortical and medullary tumours does not correspond to our immunofluorescence results. The presence of these markers does not support the theory of different embryologic origin of the cortical and subcapsular/medullary epithelial cells. Transferrin receptors were detected on only some epithelial cells of thymic 'carcinomas'. Adenocarcinoma related antigen and carcino embryonic antigen only stained a few epithelial cells of all the tumours. There is no expected correlation between the presence of epidermal growth factor receptors on cell membranes and the number of proliferative cells stained by the anti-Ki67 antibodies. Immunostainings were heterogeneous according to the epithelial thymic tumours, independent of histological classification and not yet useful for prognosis.

Objective To assess the implication of hepatitis C virus (HCV) infection in the development of autoimmune thyroid response, thyroid autoantibodies were studied in serum of HCV positive patients. Methods Anti-microsomal, anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin antibodies were evaluated in the sera of 100 patients with chronic hepatitis C (53 women and 47 men; mean age = 55±5 years). In parallel, thyroid autoantibodies were investigated in blood samples obtained from two separated control groups: age-matched HCV negative-HBV positive patients (25 women, 25 men; mean age= 47±6 years) and healthy blood donors (29 women and 21 men; mean age= 54±8 years). Results Anti-thyroid antibodies were found more frequently in HCV positive women when compared to the men (8/53= 15.1 % vs 0/47= 0%,.pConclusions This strong association between HCV infection and high levels of anti-thyroid autoantibodies in women outlines the interest of systematic detection of anti-microsomal and/or anti-TPO antibodies in this population.