Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. HCT is a definitive cure for DADA2 with > 95% survival

Hematopoietic cell transplantation cures adenosine deaminase 2 deficiency: report on 30 patients

Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-alpha) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.Transplantation and immunomodulatio

Surveillance de la circulation des arbovirus d'intérêt médical dans la région du Sénégal oriental (1988-1991)

Une étude de la circulation des principaux arbovirus d'intérêt médical a été réalisée dans la région du Sénégal oriental pendant et en dehors des périodes de transmission entre 1988 et 1991. Cette étude compare les résultats sérologiques obtenus par la recherche des IgM spécifiques (par test ELISA) dans différents villages et les souches isolées de moustiques pendant les mêmes périodes. La présence d'IgM permet d'affirmer le contact avec le virus correspondant dans les 2 à 5 mois précédant le prélèvement. Cette méthode, associée aux isolements viraux dans les lots de moustiques, permet donc une évaluation globale et rapide de la circulation des principaux arbovirus. L'épizootie à virus Zika est décrite chaque année, avec une circulation permanente chez l'homme et une souche humaine isolée en 1990. Le virus de la fièvre jaune circule de façon constante à bas bruit pendant les trois années 1988-1990 aussi bien chez l'homme que chez les moustiques. Le risque d'épidémisation lié au virus Dengue 2 dans les prochaines années est souligné : en 1990 et pour la première fois au Sénégal, deux souches humaines ont été isolées en même temps et au même endroit que de nombreuses souches de moustiques. Les autres flavivirus (West Nile, Kédougou) circulent peu. Enfin, deux arbovirus responsables de fièvres hémorragiques : fièvre de la vallée du Rift et fièvre hémorragique de Crimée-Congo ne sont qu'exceptionnellement retrouvés dans la région du Sénégal oriental. (Résumé d'auteur

Surveillance de la circulation des arbovirus d'intérêt médical dans la région du Sénégal oriental (1988-1991)

Une étude de la circulation des principaux arbovirus d'intérêt médical a été réalisée dans la région du Sénégal oriental pendant et en dehors des périodes de transmission entre 1988 et 1991. Cette étude compare les résultats sérologiques obtenus par la recherche des IgM spécifiques (par test ELISA) dans différents villages et les souches isolées de moustiques pendant les mêmes périodes. La présence d'IgM permet d'affirmer le contact avec le virus correspondant dans les 2 à 5 mois précédant le prélèvement. Cette méthode, associée aux isolements viraux dans les lots de moustiques, permet donc une évaluation globale et rapide de la circulation des principaux arbovirus. L'épizootie à virus Zika est décrite chaque année, avec une circulation permanente chez l'homme et une souche humaine isolée en 1990. Le virus de la fièvre jaune circule de façon constante à bas bruit pendant les trois années 1988-1990 aussi bien chez l'homme que chez les moustiques. Le risque d'épidémisation lié au virus Dengue 2 dans les prochaines années est souligné : en 1990 et pour la première fois au Sénégal, deux souches humaines ont été isolées en même temps et au même endroit que de nombreuses souches de moustiques. Les autres flavivirus (West Nile, Kédougou) circulent peu. Enfin, deux arbovirus responsables de fièvres hémorragiques : fièvre de la vallée du Rift et fièvre hémorragique de Crimée-Congo ne sont qu'exceptionnellement retrouvés dans la région du Sénégal oriental. (Résumé d'auteur

Clinical features and prognostic factors of spinal cord sarcoidosis: a multicenter observational study of 20 BIOPSY-PROVEN patients

International audienceSarcoidosis of the spinal cord is a rare disease. The aims of this study are to describe the features of spinal cord sarcoidosis (SCS) and identify prognostic markers. We analyzed 20 patients over a 20-year period in 8 French hospitals. There were 12 men (60 %), mostly Caucasian (75 %). The median ages at diagnosis of sarcoidosis and myelitis were 34.5 and 37 years, respectively. SCS revealed sarcoidosis in 12 patients (60 %). Eleven patients presented with motor deficit (55 %) and 9 had sphincter dysfunction (45 %). The median initial Edmus Grading Scale (EGS) score was 2.5. The cerebrospinal fluid (CSF) showed elevated protein level (median: 1.00 g/L, interquartile range (IQR) 0.72-1.97), low glucose level (median 2.84 mmol/L, IQR 1.42-3.45), and elevated white cell count (median 22/mm3, IQR 6-45). The cervical and thoracic cords were most often affected (90 %). All patients received steroids and an immunosuppressive drug was added in 10 cases (50 %). After a mean follow-up of 52.1 months (range 8-43), 18 patients had partial response (90 %), 7 displayed functional impairment (35 %), and the median final EGS score was 1. Six patients experienced relapse (30 %). There was an association between the initial and the final EGS scores (p = 0.006). High CSF protein level showed a trend toward an association with relapse (p = 0.076). The spinal cord lesion was often the presenting feature of sarcoidosis. Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. The long-term functional prognosis was correlated with the initial severit

Activated Phosphoinositide 3-Kinase δ Syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Background Activated phosphoinositide-3-kinase (PI3K) δ Syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. Objectives Report the extended spectrum of disease manifestations in APDS1 versus APDS2, compare these to CTLA-4 deficiency, NFκB1 deficiency, and STAT3 gain-of-function (GOF) disease; identify predictors of severity in APDS. Methods Data collection with the European Society for Immunodeficiencies (ESID)-APDS registry. Comparison with published cohorts of the other IEIs. Results The analysis of 170 APDS patients outlines high penetrance and early-onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA-4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. Conclusion APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEI is substantial. Some specific features distinguish APDS1 from APDS2. Early-onset is a risk factor for severe disease course calling for specific treatment studies in younger patients