Thijssen P.E.,Leiden University |
Ito Y.,Kyushu University |
Grillo G.,University Paris Diderot |
Wang J.,Leiden University |
And 31 more authors.
Nature Communications | Year: 2015
The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype. © 2015 Macmillan Publishers Limited. All rights reserved.
Kone-Paut I.,University Paris - Sud |
Darce-Bello M.,University Paris - Sud |
Shahram F.,Rheumatology Research Center |
Gattorno M.,G Gaslini Scientific Institute |
And 15 more authors.
Rheumatology | Year: 2011
Objective: To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. Methods: International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following-genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is 43 years, future follow-up duration is 54 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. Results: At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. Conclusion: The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteria. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Morandi F.,G Gaslini Institute |
Ferretti E.,G Gaslini Institute |
Castriconi R.,University of Genoa |
Dondero A.,University of Genoa |
And 4 more authors.
Blood | Year: 2011
Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G-mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56 bright and CD56 dim NK cells. sHLA-Gtreated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G down-modulated (1) CXCR3 on PB and tonsil CD56 bright and CD56 dim, (2) CCR2 on PB and tonsil CD56 bright, (3) CX 3CR1 on PB CD56 dim, (4) CXCR5 on tonsil CD56 dim, and (5) CD94/NKG2A on PB and tonsil CD56 bright and CD56 dimNK cells. Such sHLA-G-mediated downmodulations were reverted by adding anti-HLA-G or anti-ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX 3CL1 and (2) PB CD56 bright NK cells toward CCL2 and CXCL10. IFN-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G-treated NK cells. sHLA-G up-regulated secretion of (1) CCL22 in CD56 bright and CD56 dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56 dim PB NK cells. Signal transduction experiments showed sHLA-G-mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G-mediated inhibition of NK-cell functions. © 2011 by The American Society of Hematology.
Holzinger D.,University of Munster |
Kessel C.,University of Munster |
Omenetti A.,University of Genoa |
Gattorno M.,G Gaslini Scientific Institute
Nature Reviews Rheumatology | Year: 2015
Translational research approaches brought major changes to the understanding and treatment options of autoinflammatory diseases. Patients with common complex multifactorial diseases such as systemic-onset juvenile idiopathic arthritis (sJIA), and particularly those with rare monogenic autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS) or TNF receptor-associated periodic syndrome (TRAPS), benefited from a deeper understanding of the pathophysiological mechanisms and new treatment options emerging from preclinical studies. The study of IL-1 and IL-6 in this context led to novel therapies by forward translation. Conversely, effective treatment of sJIA and TRAPS with IL-1 blockade stimulated reverse translational efforts to study the pathophysiology of these cytokines in autoinflammatory diseases. These translational efforts led to the discovery of biomarkers such as S100 proteins, IL-18 or serum amyloid A, which are components of the inflammatory process, support diagnosis and allow for monitoring of disease activity, helping to predict patient outcomes. The ongoing characterization of autoinflammatory diseases in individual patients has led to classification into heterogeneous subgroups. Further characterization of relevant subgroups and the design of tailored treatment regimens, as well as the identification of new therapeutic targets and treatment options, are the major future challenges in the field of autoinflammatory diseases, particularly for paediatric rheumatologists. © 2015 Macmillan Publishers Limited.
Toplak N.,University of Ljubljana |
Dolezalova P.,General University Hospital in Prague |
Constantin T.,Semmelweis University |
Sediva A.,University Hospital Motol and 2nd Medical faculty |
And 8 more authors.
Pediatric Rheumatology | Year: 2010
Objective: To analyze the prevalence of diagnosed and suspected autoinflammatory diseases in Eastern and Central European (ECE) countries, with a particular interest on the diagnostic facilities in these countries.Methods: Two different strategies were used to collect data on patients with periodic fever syndromes from ECE countries- the Eurofever survey and collection of data with the structured questionnaire.Results: Data from 35 centers in 14 ECE countries were collected. All together there were 11 patients reported with genetically confirmed familial Mediterranean fever (FMF), 14 with mevalonate-kinase deficiency (MKD), 11 with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and 4 with chronic infantile neurological cutaneous and articular syndrome (CINCA). Significantly higher numbers were reported for suspected cases which were not genetically tested. All together there were 49 suspected FMF patients reported, 24 MKD, 16 TRAPS, 7 CINCA and 2 suspected Muckle-Wells syndrome (MWS) patients.Conclusions: The number of genetically confirmed patients with periodic fever syndromes in ECE countries is very low. In order to identify more patients in the future, it is important to organize educational programs for increasing the knowledge on these diseases and to establish a network for genetic testing of periodic fever syndromes in ECE countries. © 2010 Toplak et al; licensee BioMed Central Ltd.