Lopez-Isac E.,Institute of Parasitology and Biomedicine Lopez Neyra |
Campillo-Davo D.,Institute of Parasitology and Biomedicine Lopez Neyra |
Bossini-Castillo L.,Institute of Parasitology and Biomedicine Lopez Neyra |
Guerra S.G.,University College London |
And 70 more authors.
Annals of the Rheumatic Diseases | Year: 2015
Objectives TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. Methods This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. Results Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10-13, OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10-3, OR=0.80; p=1.27×10-3, OR=0.59; p=2.63×10-5, OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. Conclusions We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology. © 2015 BMJ Publishing Group Ltd & European League Against Rheumatism.
Duque S.G.,Madrid Norte Sanchinarro Hospital |
Lopez D.M.,Madrid Norte Sanchinarro Hospital |
De Mendivil A.O.,Madrid Norte Sanchinarro Hospital |
Fernandez J.D.,Madrid Norte Sanchinarro Hospital
Clinical Neurology and Neurosurgery | Year: 2016
Objectives Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare lesions occurring anywhere in the central nervous system (CNS). Since their description, only 55 cases have been reported. We present the largest series reviewing their imaging features, histology and potential origins. Patients and methods: four patients with histopathologically verified CAPNON are presented. Subsequently, we review all reports published with respect to study type, number of patients, clinical presentation, anatomical area (intracranial, spinal, or both), radiological features, therapy, histopathologic features, duration of follow-up, complications, and outcome. Moreover, current management of CNS CAPNON are discussed. Autopsy patients were excluded. Results Four patients with histopathologically verified diagnosis of CAPNON are presented between 46-73 years-old. Three of them were located in the spinal cord (levels C3, D2, and L2) and one intracranial (left atrium). The spine ones were diagnosed due to radicular pain, paraparesis and numbness in lower limb, the intracranial because of intense headache. The differential diagnosis included cavernous malformation, in the case of the lumbar CAPNON this suspicion put back the surgery six months. All cases were surgically treated with complete resection. No recurrence showed at the 12-month follow-up. A total of retrospective 30 articles were selected: 10 case series (33.33%) and 20 reports of single cases (66.66%). The 30 articles and our additional cases added up to a total of 27 patients with spinal CAPNON and 32 patients with intracranial CAPNON. All patients were treated surgically. A follow-up, conducted in 48 patients, showed no signs of recurrence in 46 of the 48. Conclusions Calcifying pseudoneoplasms are rare benign lesions of yet unknown origin. They should be taken into consideration in the differential diagnosis of calcified lesions because an inaccurate diagnosis can result in potentially harmful and unnecessary therapies, as prognosis for these lesions is generally favorable. © 2016 Elsevier B.V. All rights reserved.