[The main autoimmune bullous diseases]. / Les principales maladies bulleuses auto-immunes.

Autoimmune bullous diseases are disorders in which the immune system mistakenly attacks certain molecules that act as "glue" in the various layers of the skin, leading to the formation of bullae or vesicles. A bulla is a liquid-containing lesion over five millimeters in size on the skin or mucous membranes. It forms due to a loss of cohesion between the epidermis and dermis, or between keratinocytes within the epidermis. Diagnosis is based on biopsies, which show the presence of autoantibodies and the depth of skin detachment. A blood test can be used to identify circulating autoantibodies.

[Dysimmune manifestations associated with myelodysplastic neoplasms and chronic myelomonocytic leukaemias]. / Manifestations dysimmunitaires associées aux syndromes myélodysplasiques et leucémies myélomonocytaires chroniques.

Systemic inflammatory or autoimmune diseases (SIAD) are observed in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), with a broad clinical spectrum including asymptomatic biological abnormalities, isolated inflammatory clinical manifestations (recurrent fever, arthralgia, neutrophilic dermatoses…) or identified systemic diseases (giant cell arteritis, recurrent polychondritis…). Recent advances in molecular biology have shed new light on the pathophysiological mechanisms that link inflammatory manifestations and myeloid hemopathies, particularly in VEXAS syndrome following the identification of somatic mutations in the UBA1 gene, or in neutrophilic dermatoses with the concept of myelodysplasia cutis. Although the presence of SIAD does not seem to affect overall survival or the risk of transformation into acute myeloid leukemia, their treatment remains a challenge given the frequent high level of corticosteroid dependence as well as the poor efficacy and tolerance (cytopenias, infections) of conventional immunosuppressive agents. Recent prospective data supports the interest of a therapeutic strategy using demethylating agents and notably azacitidine to target the pathological clone.

[Autoimmune and inflammatory pathologies associated with systemic scleroderma: Clinical, serological and prognostic profiles. Bi-centric retrospective series in the PACA region]. / Pathologies auto-immunes et inflammatoires associées à la sclérodermie systémique : profils cliniques, sérologiques et pronostiques. Série rétrospective bi-centrique en région PACA.

INTRODUCTION: Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. METHODS: We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. RESULTS: The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. CONCLUSION: SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up.

[Management of HPV-induced cervical lesions in immunosuppressed patients - Review of the literature]. / Prise en charge des lésions cervicales HPV induites chez les patientes immunodéprimées ­ Revue de la littérature.

INTRODUCTION: Current French recommendations for the management of cervical lesions related to human papilloma virus (HPV) infection are limited to general population. Patients who are immunocompromised appear to be at increased risk of induced HPV lesions. The objective of this review is to summarize the various existing data about risk of induced HPV lesions in immunocompromised patients to specify the management. METHODS: The Medline database was searched through the Pubmed portal, as well as the recommendations of various international learned societies. RESULTS: Situations with an increased risk are regardless of treatment: Human Immunodeficiency Virus (HIV) infection, transplants, lupus. Patients with chronic inflammatory bowel disease (IBD) and rheumatoid arthritis are at increased risk only when immunosuppressive therapy is required. Screening for dysplasic intraepithelial lesions in HIV+ patients should be more sustained than in the general population. Due to lack of data, recommendations for other conditions have been extrapolated from the management of HIV+ patients. HPV vaccination is effective in these populations, particularly at times when the immune system is the most effective. DISCUSSION: Identified immunocompromised populations are at higher risk of induced HPV lesions due to an incomplete immune response and should be screened on a sustained basis. In addition, HPV vaccination should be encouraged.

[Multiple sclerosis and daily care]. / Sclérose en plaques et soins au quotidien.

Multiple sclerosis is a progressive disease that is too often associated with the image of a wheelchair. However, this image does not reflect the reality of most patients. Even with basic treatment, relapses can persist. Less visible, fluctuating and often misunderstood symptoms can be the source of negative judgements: chronic fatigue labelled as laziness or as a lack of willpower, balance problems interpreted as drunkenness, mood fluctuations likened to hysteria, etc. The consequences of the disease are therefore physical, psychological and socio-economic. The aim is to preserve the quality of daily life. There are a number of aids and treatments available.

[Supporting the adaptation to the announcement of a diagnosis of multiple sclerosis (2/2)]. / Accompagner l'adaptation à l'annonce d'une sclérose en plaques (2/2).

The emotional reactions that arise when a diagnosis of multiple sclerosis is made are repeated at each stage of the pathology. They confront the person with a reality they thought they had mastered. Fighting with the disease means continuing to live one's personal, family, love and professional life. It is a matter of positive thinking by becoming aware of one's limits and finding the right balance between one's desires and one's capacities. The relationship of trust developed with the various professionals who will accompany the patient throughout his or her treatment is essential.

[Supporting the adaptation to the announcement of multiple sclerosis]. / Accompagner l'adaptation à l'annonce d'une sclérose en plaques (1/2).

Multiple sclerosis (MS) is a disease that most often begins in young adulthood. With at least 2,500 new cases diagnosed each year in France, it is the leading cause of severe non-traumatic disability among young adults. The announcement of MS constitutes a brutal intrusion into the life of the subject. The carers accompany the process of cognitive and emotional adjustment that is inevitable in order to learn to live with the disease.

[Thrombin generation assay in autoimmune disease]. / Place du test de génération de thrombine dans les maladies auto-immunes.

Thrombin generation assay (TGA) is a useful tool to evaluate the initiation, propagation and inhibition of coagulation. TGA is a global test that is used to assess hemorrhagic risk in hemophilia patients, but it can also be used to study hypercoagulable states. The interest of TGA is to screen for cardiovascular risk, which is regularly associated with autoimmune disease (AID) such as antiphospholipid syndrome. Indeed, TGA has been used to evaluate hypercoagulability in patients with antiphospholipid syndrome treated with rivaroxaban versus warfarin. In other AIDs without thrombotic events, TGA measurement is elevated, mainly in rheumatoid arthritis (RA), systemic lupus erythematosus and Behçet's disease. These findings in RA are correlated with the inflammatory activity of the disease. In systemic lupus erythematosus and Behçet's disease, TGA appears to reflect disease activity. In conclusion, TGA remains relatively under used in the clinical evaluation of AID, but it could play a greater role in the evaluation of certain potentially thrombogenic treatments in AID. Finally, TGA helps measuring AID activity, due to the clearlink between coagulation and inflammation, despite some limitations of interpretation mainly due to a lack of standardization.

[Polymyalgia rheumatic and chronic myelomonocytic leukemia]. / Pseudo-polyarthrite rhizomélique satellite d'une leucémie myélomonocytaire chronique.

INTRODUCTION: Myelodysplasia (MDS) can occur as systemic manifestations such as connective tissue diseases or vasculitis. Rheumatological manifestations are also described in such context. Herein, we report the observation of a patient with chronic myelomonocytic leukemia (CMML) who developed systemic manifestations: polymyalgia rheumatica and pericarditis. CASE REPORT: A 78-year-old patient was referred for the exploration of two months history of inflammatory shoulder pain associated with biological inflammatory syndrome. He presented with asthenia, anorexia and loss of 5kg in one month. He had a three years follow-up for a CMML without any specific treatment. All of the explorations carried out showed a typical polymyalgia rheumatica. A pericardial effusion requiring emergency drainage was synchronously diagnosed. All the symptoms occurred during a worsening of his hematological disease. The rheumatological manifestation was favorable after a short corticosteroid therapy and pericarditis did not recur after 2 years of follow-up. CONCLUSION: It should be necessary to screen patients for MDS in a context of systemic manifestation, especially in elderly patients with an abnormal blood count (cytopenia, macrocytosis and monocytosis).

[Narcolepsy: From the discovery of a wake promoting peptide to autoimmune T cell biology and molecular mimicry with flu epitopes]. / Narcolepsie : une maladie auto-immune affectant un peptide de l'éveil liée à un mimétisme moléculaire avec des épitopes du virus de la grippe.

Narcolepsy-cataplexy was first described in the late 19th century in Germany and France. Prevalence was established to be 0.05 % and a canine model was discovered in the 1970s. In 1983, a Japanese study found that all patients carried HLA-DR2, suggesting autoimmunity as the cause of the disease. Studies in the canine model established that dopaminergic stimulation underlies anti-narcoleptic action of psychostimulants, while antidepressants were found to suppress cataplexy through adrenergic reuptake inhibition. No HLA association was found in canines. A linkage study initiated in 1988 revealed in hypocretin (orexin) receptor two mutations as the cause of canine narcolepsy in 1999. In 1992, studies on African Americans showed that DQ0602 was a better marker than DR2 across all ethnic groups. In 2000, hypocretin-1/orexin A levels were measured in the cerebrospinal fluid (CSF) and found to be undetectable in most patients, establishing hypocretin deficiency as the cause of narcolepsy. Decreased CSF hypocretin-1 was then found to be secondary to the loss of the 70,000 neurons producing hypocretin in the hypothalamus, suggesting immune destruction of these cells as the cause of the disease. Additional genetic studies, notably genome wide associations (GWAS), found multiple genetic predisposing factors for narcolepsy. These were almost all involved in other autoimmune diseases, although a strong and unique association with T cell receptor (TCR) alpha and beta loci were observed. Nonetheless, all attempts to demonstrate presence of autoantibodies against hypocretin cells in narcolepsy failed, and the presumed autoimmune cause remained unproven. In 2009, association with strep throat infections were found, and narcolepsy onsets were found to occur more frequently in spring and summer, suggesting upper away infections as triggers. Following reports that narcolepsy cases were triggered by vaccinations and infections against influenza A 2009 pH1N1, a new pandemic strain that erupted in 2009, molecular mimicry with influenza A virus was suggested in 2010. This hypothesis was later confirmed by peptide screening showing higher activity of CD4+ T cell reactivity to a specific post-translationally amidated segment of hypocretin (HCRT-NH2) and cross-reactivity of specific TCRs with a pH1N1-specific segment of hemagglutinin that shares homology with HCRT-NH2. Strikingly, the most frequent TCR recognizing these antigens was found to carry sequences containing TRAJ24 or TRVB4-2, segments modulated by narcolepsy-associated genetic polymorphisms. Cross-reactive CD4+ T cells with these cross-reactive TCRs likely subsequently recruit CD8+ T cells that are then involved in hypocretin cell destruction. Additional flu mimics are also likely to be discovered since narcolepsy existed prior to 2009. The work that has been conducted over the years on narcolepsy offers a unique perspective on the conduct of research on the etiopathogeny of a specific disease.

TITLE: Narcolepsie : une maladie auto-immune affectant un peptide de l'éveil liée à un mimétisme moléculaire avec des épitopes du virus de la grippe. ABSTRACT: La narcolepsie et la cataplexie sont décrites pour la première fois à la fin du XIXe siècle en Allemagne et en France. La prévalence de la maladie est établie à 0,05 % et un modèle canin est découvert dans les années 1970. En 1983, une étude japonaise révèle que les patients narcoleptiques sont porteurs d'un marqueur génétique unique, l'antigène leucocytaire HLA-DR2, suggérant l'auto-immunité comme cause de la maladie. Il faudra attendre 1992 pour qu'il soit montré, grâce à une étude chez des patients afro-américains, que DQ0602, un autre gène HLA, est la véritable cause de cette association. Des études pharmacologiques conduites sur le modèle canin établissent que la stimulation dopaminergique est le mode d'action des stimulants sur l'éveil, tandis que les antidépresseurs suppriment la cataplexie en inhibant la recapture adrénergique. Aucune association HLA n'est cependant mise en évidence chez les chiens, suggérant une cause distincte de la maladie humaine. Une étude de liaison génétique chez les chiens, initiée en 1988, révèle en 1999 que la narcolepsie canine est causée par des mutations du récepteur 2 de l'hypocrétine (orexine). En 2000, l'hypocrétine-1/orexine A est mesurée dans le liquide céphalo-rachidien (LCR) et on découvre qu'elle est indétectable chez la plupart des patients narcoleptiques, établissant qu'un déficit hypocrétinergique est la cause de la narcolepsie humaine. La diminution de l'hypocrétine-1 dans le LCR, secondaire à la perte des 70 000 neurones hypothalamiques produisant l'hypocrétine, est démontrée, ce qui, avec l'association au locus HLA, suggère qu'une destruction immunitaire de ces cellules est la cause de la maladie. D'autres études génétiques, notamment d'association à l'échelle du génome (GWAS), révèlent l'existence de nombreux facteurs génétiques prédisposant à la narcolepsie, la plupart étant également impliqués dans d'autres maladies auto-immunes. Une association forte et unique avec les loci des récepteurs lymphocytaires T (TCR) alpha et bêta est aussi observée, suggérant un rôle prépondérant des lymphocytes T. En dépit de nombreux efforts, toutes les tentatives visant à démontrer la présence d'auto-anticorps contre les cellules à hypocrétine dans la narcolepsie échouent, et la cause auto-immune présumée de cette maladie reste à l'état d'hypothèse. À la suite de la grippe pandémique influenza A pH1N1 en 2009, de nombreux cas de narcolepsie apparaissent, suggérant un mimétisme moléculaire avec le virus de la grippe qui pourrait déclencher la maladie auto-immune. Cette hypothèse est confirmée par un criblage peptidique montrant une plus grande réactivité des lymphocytes T CD4+ à un segment spécifique de l'hypocrétine (HCRTNH2) et une réactivité croisée des TCR correspondants à un segment d'hémagglutinine de pH1N1 qui partage une homologie avec HCRTNH2. De façon remarquable, le TCR le plus fréquent dans la population et qui reconnaît ces antigènes contient des séquences TRAJ24 ou TRVB4-2, segments modulés par des polymorphismes génétiques associés à la narcolepsie dans les études GWAS. Il est probable que les lymphocytes T CD4+ autoréactifs avec HCRTNH2 recrutent par la suite des lymphocytes T CD8+ qui détruisent les cellules à hypocrétine. On peut s'attendre à ce que d'autres séquences mimiques grippales inconnues soient découvertes prochainement puisque la narcolepsie existait avant 2009. Ces découvertes démontrent enfin la cause auto-immune de la narcolepsie. Les travaux menés au cours des années sur la narcolepsie offrent une perspective unique sur la conduite de la recherche sur l'étiopathogénie d'une maladie bien identifiée.

[Microscopic Colitis]. / Mikroskopische Kolitis.

Microscopic colitis (MC) is still an underestimated cause of chronic, non-bloody watery diarrhea. It is typically manifested in elderly patients with a female predominance. The incidence of microscopic colitis has been increasing. The aetiology and pathophysiology remain unclear. Conditions associated with it include autoimmune diseases. There may be a genetic predisposition, as familial cases have been described. As implicated by the name microscopic colitis, the diagnosis is found by histological examination. There are mainly two subtypes, the lymphocytic colitis (LC) and the collagenous colitis (CC). Even if the condition's long-term course is benign, a chronic recurrent course of the symptoms is frequent. Due to the symptoms, there is an impairment of patient's health-related quality of life. A correct diagnosis and therapy is therefore mandatory. The aim of this paper is to create awareness for microscopic colitis.

[Scleritis and systemic diseases: What should know the internist?] / Sclérites et maladies systémiques : que doit savoir l'interniste ?

Scleritis is an inflammatory disease of the sclera; outer tunic of the eye on which the oculomotor muscles are inserted. It can be associated with a systemic disease up to one time out of 3. These associated diseases are mainly rheumatoid arthritis, vasculitis, including granulomatosis with polyangiitis in the first line and spondyloarthropathies. Before mentioning such an etiology, it is necessary to eliminate an infectious cause, mainly herpetic, which is regularly underestimated. The classification of scleritis is clinical. We distinguish between anterior scleritis and posterior scleritis. Anterior scleritis is diffuse or nodular, usually of good prognosis. Anterior necrotizing scleritis with inflammation is often associated with an autoimmune disease, necrotizing scleritis without inflammation usually reflects advanced rheumatoid arthritis. The treatment of these conditions requires close collaboration between internists and ophthalmologists to decide on the use of corticosteroid therapy with or without immunosuppressors or biotherapies.

MicroRNAs in type 1 diabetes: new research progress and potential directions.

MicroRNAs (miRNAs) are a class of noncoding single-stranded RNA molecules encoded by endogenous genes of about 22 nucleotides, which are involved in post-transcriptional gene expression regulation in animals and plants. Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of ß cells are destroyed, and a large number of studies have shown that miRNAs are involved in the pathological mechanism of T1D. In this review, we searched the related research in recent years and summarized the important roles of miRNAs in T1D diagnosis and treatment. Furthermore, we summarized the current understanding of miRNA-mediated regulation mechanisms of gene expression in the T1D pathogenesis as well as related signaling pathways with a focus on the important roles of miRNAs and their antagonists in T1D pathogenesis, and brought insight into the potential therapeutic value of miRNAs for T1D patients. In view of the important roles of miRNAs in T1D pathology, disordered miRNAs may be important diagnostic markers and therapeutic targets for patients with T1D.

[Type I interferonopathies. Literature review]. / Les interféronopathies de type I. Mise au point et revue de la littérature.

Thanks to the tremendous progress of genetics, a new field of inherited inflammatory disorders related to an overproduction of interferon has recently emerged. The so-called type I interferonopathies represent an heterogeneous group of Mendelian diseases presenting with various features starting in childhood, although the diagnosis can also be made later in life. Several clinical and biological characteristics are shared across these patients such as a positive interferon (IFN) signature and neurological and cutaneous involvement, some of which display organ specificity. Treatment is challenging, but IFN-targeting therapies represent a promising option in these severe diseases.

[Influence of epigenetic in Sjögren's syndrome]. / Épigénome et syndrome de Gougerot-Sjögren.

Sjögren's syndrome (SS) is a systemic autoimmune epithelitis with a major female incidence, and characterized by a dry syndrome, impaired quality of life, visceral involvement, and lymphoma for the most aggressive cases. During this process, epithelial cells acquire the capacity to produce cytokines, chemokines, and autoantigens which can in turn be presented to the immune system. Consequently, this epithelitis is accompanied by lymphocytic infiltrations leading to the formation of pseudo-follicles in which self-reactive B lymphocytes are present. The recent integration of genomic and especially of epigenomic data, which make it possible to analyze the different cellular partners, opens new perspectives and allows to a better understanding of this complex and still incurable disease.

[Vogt-Koyanagi-Harada disease]. / La maladie de Vogt-Koyanagi-Harada.

Vogt-Koyanagi-Harada (VKH) disease is defined as a severe bilateral, chronic granulomatous panuveitis associated with serous retinal detachments, disk edema, and vitritis, with central nervous system, auditory, and integumentary manifestations. It is an autoimmune inflammatory condition mediated by T cells that target melanocytes in individuals genetically susceptible to the disease. Vogt-Koyanagi-Harada disease presents clinically in 4 different phases: prodromal, acute inflammatory, chronic, and recurrent, with extraocular manifestations including headache, meningitis, hearing loss, poliosis, and vitiligo. Optical coherence tomography (OCT) allows earlier diagnosis of VKH disease by revealing heterogeneous exudative detachments of the retina in the acute stage and choroidal thickening, and by demonstrating choroidal thinning in the chronic stage. Treatment of this disease is initially with intravenous corticosteroids, with, if needed, a transition to immunosuppressant drugs for long-term control. Patients with VKH disease can have good final visual outcomes if treated promptly and aggressively.

[Epidermolysa bullosa acquisita and graft-versus-host disease]. / Épidermolyse bulleuse acquise et réaction du greffon contre l'hôte.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare acquired blistering disorder caused by production of auto-antibody directed against type-VII collagen. Autoimmune disorders can occur after allogenic bone marrow transplantation as manifestations associated with chronic graft-versus-host disease (GVHD). To date, there have been 10 cases reported in the literature concerning autoimmune blistering diseases following allogenic stem-cell transplants. Herein we describe a new case involving EBA. OBSERVATION: A 46-year-old woman developed EBA 4 years after allogenic cord blood transplantation for non-Hodgkin T-cell lymphoma complicated by acute digestive and cutaneous GVHD. At physical examination, she had some cutaneous blisters on the abdomen, arms and face, as well as numerous erosions in the buccal cavity. Direct immunofluorescence microscopy revealed linear IgG and C3 deposits along the dermal-epidermal basement membrane zone. Indirect immunofluorescence showed weak IgG G4 anti-basement membrane zone antibodies, which reacted with the dermal side of 1M NaCl-split skin; the autoantibodies were directed against type-VII collagen. This second case of EBA was evocative of a GVHD blistering disease. After the therapeutic failure of dapsone and of combined mycophenolate-prednisone, treatment with rituximab proved effective. DISCUSSION: EBA may form part of the autoimmune signs associated with chronic GVH. The destruction of basement membrane and of epidermal basal cells that occurs in GVH could give rise to autoimmune bullous disease. However, in our patient, in whom manifestation of chronic GVH was restricted to the lungs, it is difficult to rule out the fortuitous onset of EBA, which presented at a sizeable interval after acute GVH.

Ecos del deseo en el cuerpo, el enigma de la autoinmunidad / Desire echoes in the body, autoinmunity enigma / Échos du désir dans le corps, l'énigme de l'auto-immunité

El presente artículo es el resultado de la investi-gación Afección autoinmune y goce, llevada a cabo en el marco de la Maestría en Investigación psicoanalítica de la Universidad de Antioquia (Colombia). El propósito del mismo es desarrollar uno de los hallazgos de la investigación, según el cual habría una posible articulación entre los enigmas que plantean las afecciones autoinmu-nes y los avatares del deseo, los cuales tendrían un eco en el cuerpo. Lo anterior, partiendo de la concepción psicoanalítica del cuerpo como terri-torio de lo psíquico, como lugar de inscripción de las huellas que se producen en la relación al Otro, en la que se juega lo concerniente al goce y al deseo...

This article is the result of Autoimmune Condition and Jouissance research, carried out as part of the Master in Psychoanalytic Research of the University of Antioquia, Colombia. The purpose is to develop one of the research findings, according to which there would be a possible link between the enigmas posed by autoimmune conditions and the vicissitudes of desire which would have an echo in the body. This is based on the psy-choanalytic idea of the body as a psychic territory, place of the inscription of the traces that occur in the relation to the Other, involving jouissance and desire...

Cet article est le résultat du projet de recherche Maladie auto-immune et jouissance, effectué dans le cadre du Master en recherche psycha-nalytique de L´Université d´Antioquia à Medellín, Colombie. Le but de cet article est donc de déve-lopper l’un des résultats de ladite recherche, selon lequel il y aurait une articulation entre les énigmes posées par les maladies auto-immunes et les vicissitudes du désir, lesquelles auraient un écho sur le corps. Cette approche se base sur la conception psychanalytique du corps en tant que territoire du psychisme, comme un lieu d’inscription des traces que la relation avec l´Autre produit, où ce qui concerne la jouissance et le désir est en jeu...