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En aquest reportatge es fa un recorregut a l’experiència d’uns cinquanta anys als espais expositius, aules i altres recintes, de la Universitat Autònoma de Barcelona. Una tasca en la qual s’implicà des del professorat, alumnes, artistes contemporanis, fins el rectorat de la Universitat, i que representà per l’alumnat una formació pràctica als seus estudis de futurs historiadors i crítics d’art.

Sobre els dibuixos de Mir no hi ha cap estudi o inventari seriós que permeti fer-ne una aproximació fiable, per tant aquest treball intenta apropar-nos a conèixer el nombrós volum de dibuixos que l’artista realitzà i posar sobre la taula quina ha estat la problemàtica més rellevant que els envoltà.

El present estudi torna a la casa Trinxet per aportar nova informació sobre les pintures que estaven a les golfes i les teles que ornamentaven el menjador. Les pintures de les golfes van estar subjectes al contracte entre Joaquim Mir i el seu oncle, Avelino Trinxet, a partir de 1900 i liquidat entorn l’any 1917, el qual dona a conèixer el paper que jugà l’oncle. Les enormes pintures del menjador van ser desmantellades i quarterades per a ser posades a la venda l’any 1968, quan es produí l’enderroc de la casa. En ambdós casos es tracta de fer un seguiment del destí d’aquestes pintures.

Objective.Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD.Methods.Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively.Results.Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06–1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47–0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027).Conclusion.Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.

Internet has become a widely used tool by patients seeking information on different diseases. The information regarding lupus patients' Internet use is scarce. This study aims to explore the attitudes and practices of lupus patients in southern Spain, regarding Internet use to find health-related information. A survey was carried out including 150 patients from six Andalusian Hospitals. To search for information, 67.3 % of the patients used Internet. The proportion of female Internet users was higher (69.3 vs 46.2 %), particularly those belonging to a patients' association (81.8 vs 32.7 %), and are regular users of Internet (80.2 vs 44.4 %); 37.5 % thought the information found in the Internet was of little use or not useful at all, and 58 % of the respondents stated that the information found caused them concern while for 27 %, it was a relief. Most patients preferred the information given by their physicians (63.6 %); 33.9 % considered that the information from both sources was complementary, and 2.5 % preferred the information obtained from the Internet. A percentage of 85.3 of the patients would like their physicians to provide them with information on high-quality sites regarding their illness. Lupus patients make frequent use of the Internet to look for information on their disease. Considering this, and because better-informed patients follow more precisely the indications given by the physician, medical staff should collaborate in the development of high-quality sites for the patient to have additional sources of information.

To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2–IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56 %) and non-responder (45.45 %) SLE patients (p = 0.010, odds ratio (OR) = 6.10 [1.28–29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p = 0.024, OR = 3.53 [1.06–11.64]). Our results show for a first time that IL2–IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

Rituximab has become a pivotal treatment for systemic autoimmune diseases. The aim of this study was to determine whether the genetic variant -174 IL-6 contributes to differences in the response to rituximab in patients with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory myopathies, anti-neutrophil cytoplasmic antibody-mediated vasculitis, systemic sclerosis, Sjöegren's syndrome, rheumatoid arthritis, and autoimmune hemolytic anemia. DNA samples from 144 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for -174 IL-6 (rs1800795) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after the first infusion with rituximab, we evaluated the response to the drug: 60.4% of the patients showed a complete response, partial 27.8%, and 11.8% did not respond to the treatment. The CC genotype frequency was significantly increased in nonresponders with respect to responders (23.5% vs. 7.1%, respectively; p=0.049; odds ratio (OR)=4.03, 95% confidence intervals (CI) 0.78-16.97). According to the genotype distribution, rituximab was effective in 69.2% of the CC carriers, 91.9% of the CG carriers, and 88.4% of the GG carriers. A similar trend was observed when SLE patients were analyzed separately (27.3% carried CC homozygosis in nonresponders and 6.9% in responders; p=0.066; OR=5.10, 95% CI 0.65-31.73). Rituximab was effective in 62.5% of the CC carriers, 88.9% of the GC carriers, and 90% of the GG carriers. These results suggest that -174 IL-6 (rs1800795) gene polymorphism plays a role in the response to rituximab in systemic autoimmune diseases. Validation of these findings in independent cohorts is warranted.

To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis.We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P0.05), and sicca syndrome (37.5% vs 14.5%, P0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor.The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements.

We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.

The functional variant R620W of the protein tyrosine phosphatase non receptor-22 (PTPN22) gene plays an important role in susceptibility to several immuno-mediated pathologies. Behçet's disease (BD) is a complex disease related to the immune system with a demonstrated genetic base. The HLA class I genes are the most important genetic factors in BD although other genes are also involved in the susceptibility to this disease. The PTPN22 has been proposed as a candidate gene in BD but this association has not been clearly demonstrated yet. The aim of this study was to assess the association of PTPN22 with BD.A cohort composed of 404 Spanish BD patients and 1517 unrelated healthy individuals ethnically matched was genotyped in rs2476601 (R620W). Five tag SNPs: rs1217412, rs2476599, rs3789607, rs3765598 and rs1217419 (spanning a 57 Kb region between 3'UTR and 5'UTR) and rs2488457 (located at the promoter region) were also studied in order to perform a screening of the complete gene. Genotyping was performed using TaqMan® assays. The rs2476601 data were included in a meta-analysis together with those published till the date. The rest of SNPs were used in a case-control study.No evidence of the association of rs2476601 with BD in the meta-analysis (P = 0.504 in the model of alleles) was found. In the case-control study, no statistically significant differences were observed when comparing the distribution of variants in patients and controls.Our results do not support a major role of the PTPN22 gene in BD.

Behçet's disease (BD) is an immune-mediated and complex disease associated with HLA class I and other genes. The aim of this study was to contribute to a better understanding of the relationship of the 32-bp deletion in the CCR5 gene (CCR5Δ32) and this disease by conducting a case-control study in the Spanish population and also a meta-analysis including all the studies available to date.A cohort composed of 348 BD Spanish patients and 477 unrelated healthy and ethnically matched individuals were genotyped in CCR5Δ32 using polymerase chain reaction (PCR) and capillary electrophoresis with fluorescent detection. In the meta-analysis, data from a total of seven populations extracted from four previous studies along with data of the present study were included.Regarding the case-control study, no statistically significant differences were observed when the patient and control groups were compared (allelic model: 0.07 in patients vs. 0.06 in controls, p=0.303). In the meta-analysis, no evidence of association of the CCR5Δ32 polymorphism with BD was observed (pMH=0.091; OR=1.22; 95%CI 0.98 to 1.52 in the allelic model).The results of this meta-analysis discard a major role of the CCR5Δ32 polymorphism in BD.

We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 +/- 12 years (range, 16-79 yr), and with a mean follow-up of 9 +/- 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS.

Fundamento y objetivo: Describir y comparar las caracteristicas demograficas, clinicas y analiticas de una serie de casos de sindrome antifosfolipidico (SAF; criterios de Harris) primarios y secundarios atendidos en 2 centros espanoles de referencia. Pacientes y metodo: Se describen 112 pacientes con SAF ?en 50 casos primario (SAFP) y en 62 secundario (SAFS)?, de los que 56 (90%) presentaban lupus eritematoso sistemico, controlados en los 2 centros de referencia de la provincia de Malaga entre 1989 y 2000. Los datos se recogieron de las historias por los clinicos responsables mediante un protocolo preestablecido. Resultados: La edad en el momento del estudio fue similar en ambos grupos (42,3 [14,7] anos para el grupo total). Los pacientes con SAFS comenzaron su enfermedad mas jovenes (29,6 [12,6] frente a 37,0 [13,9] anos en el SAFP) y tuvieron mayor tiempo de evolucion de la enfermedad (143,3 [115,5] frente a 83,5 [73,5] meses en el SAFP). Hubo un predominio de sexo femenino (un 84% en el SAFS y un 60% en el SAFP). La prevalencia de fenomenos tromboticos arteriales (43%) y venosos (39%), perdidas fetales (40%), parto prematuro (9%), anticuerpos anticardiolipina (88%) y anticoagulante lupico (54%) fueron similares en ambos grupos. El SAFS presento mayor prevalencia de anticuerpos antinucleares, trombocitopenia y anemia hemolitica. Conclusiones: Los pacientes con SAFP y SAFS no presentan diferencias en las manifestaciones clinicas ni en las alteraciones inmunologicas caracteristicas del sindrome. Los pacientes con SAFS son mas jovenes al comienzo de su enfermedad y tienen mayor predominio del sexo femenino. Nuestros pacientes difieren de los de otras series espanolas publicadas, lo que se explica por la existencia de sesgos de seleccion y clasificacion.

Behçet's disease (BD) is an immune-mediated and complex disease which has been associated with HLA class I molecules although other genes such as IL23R and IL10 have also been involved in the susceptibility to BD. Recently, an association of variants of the JAK1 and TNFAIP3 genes with the disease has been reported in the Chinese Han population. The aim of the present work was to asses whether the association described in Asian populations is replicated in Europeans.This study includes a total of 1155 Spanish subjects of European origin (372 BD and 783 unrelated healthy individuals). Patients were recruited from different hospitals and controls were collected in the same geographic regions and they matched with patients in age and gender. A total of five SNPs, two in the JAK1 gene: rs2780815 and rs310241 and the other three in the TNFAIP3: rs10499194, rs9494885 and rs610604, were included in this study. The genotyping of these SNPs was performed using a real time PCR system (TaqMan® SNP Genotyping Assays).No statistically significant differences were found when the patient and control groups were compared. The distribution of the risk alleles was similar in patients with and without eye manifestations and in patients with and without HLA-B*51.The association of variants of the genes JAK1 and the TNFAIP3 with BD which has been described in the Chinese population was not replicated in Europeans.

Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

Introduction According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet’s disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. Methods This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ2 test. Results In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population. Conclusion Different HLA specificities are associated with Behçet’s disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease., This work was supported by Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547).

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10-8, OR = 1.22, CI 95% = 1.14-1.30; rs2004640: P = 4.60×10-7, OR = 0.84, CI 95% = 0.78-0.90; rs10488631: P = 7.53×10-20, OR = 1.63, CI 95% = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10-22, OR = 1.75, CI 95% = 1.56-1.97) better explained the observed association (likelihood P-value = 1.48×10-4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific. © 2013 Carmona et al.

Rituximab is being used as treatment for systemic autoimmune diseases. The objective of this study was to determine whether the genetic variant in the Fc gamma-receptor III a (FCGR3A) gene, 158F/V, contributes to the observed variation in response to rituximab in patients with systemic autoimmune diseases. DNA samples from 132 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for FCGR3A-158F/V (rs396991) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after infusion with rituximab we evaluated the response to the drug: 61% of the patients showed a complete response, partial 27% and 12% did not respond to the treatment. A statistically significant difference was observed in V allele frequency between responder (38%) and nonresponder (16%) patients (p=0.01; odds ratio [OR]=3.24, 95% confidence interval [CI] 1.17-11.1). Rituximab was also more effective in V allele carriers (94%) than in homozygous FF patients (81%): p=0.02; OR=3.96, 95% CI 1.10-17.68. These results suggest that FCGR3A-158F/V (rs396991) gene polymorphism play a role in the response to rituximab in autoimmune diseases. Validation of these findings in independent cohorts is warranted.

Objectives: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results: A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions: The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

Behcet disease (BD) is a multifactorial disorder with a highest prevalence among people with Mediterranean or Asian ancestry having association with HLA-B51 and other HLA and non-HLA loci.1–4 Very recently, one genome-wide association study (GWAS) identified the GIMAP locus, which encoded proteins involved in development of the T and B lymphocytes, as associated with the disease in the Asian populations.5 To investigate whether this association is replicated in Europeans, a total of 1086 (326 patients and 760 controls) Spanish individuals of European origin were genotyped after obtaining written informed consent and approval from the local ethical committees of all the institutions involved. Patients fulfilled the 1990 International Study Group classification criteria for Behcet’s disease,6 and the group was composed of 44.5% men with the following clinical features: 100% had oral ulcers, 63.6% genital ulcers, 58.7% uveitis, 48% arthritis, 20.2% vascular, 21.9% neurological and 19.2% gastrointestinal involvement. Regarding HLA association, in addition to B*51 (p

Background Behcet9s disease (BD) has been consistently associated with HLA class I molecules, specifically, with HLA-B51. However, the role of others HLA class I molecules remains controversial. The current methods of genotyping permit to deduce the HLA typing of a large number of individuals by imputation by using data obtained from high throughput platforms. This approach has improved the knowledge of the association of HLA with the susceptibility to immune-mediated diseases. Objectives Review of the association of HLA region with BD by comprehensive reanalysis with using a novel imputation method [1,2]. Methods The HLA typings of 1794 individuals (277 patients and 1517 healthy controls) were imputed from SNPs genotyping data obtained by Human Immuno DNA Analysis BeadChip Kit (Immunochip). The statistical analyses were performed with PLINK and R. Results The strongest association signals were observed in the HLA-B region, specifically, rs1050502 represented the highest peak (p=7.73 x 10 -24 , OR=4.029, 95%CI 3.123 to 5.198). According to the analysis performed, the amino-acid positions 97 in the HLA-B and 66 HLA-A molecules are the most relevant for the disease susceptibility. Conclusions HLA-B and HLA-A are associated with the susceptibility to BD References Raychauduri S, Sandor C, Stahl EA, et al. (2012) Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Gen 44,291-296 Jia X, Han B, Onengut-Gumuscu S, et al. (2013) Imputing amino acid polymorphisms in human leukocyte antigens. PloS one 8, e64683 Disclosure of Interest None declared

We decided to describe the demographic, clinical and laboratory characteristics of a series of patients with antiphospholipid syndrome (APS) (Harris criteria) and review other Spanish published series.We describe 112 patients with APS, 50 primary (PAPS) and 62 secondary (SAPS) -56 (90%) to systemic lupus erythematosus (SLE)-, monitorized in two referral centers in Malaga (Spain) from 1989 to 2000. All data were obtained from the medical records by means of a protocol.The age was similar in both groups (42.3 [14.7] years for the whole series). Patients with SAPS had an earlier onset of the disease (29.6 [12.6] years, vs 37.0 [13.9] years in PAPS) and they had a longer evolution of the disease (143.3 [115.5] months, vs 83.5 [73.5] months in PAPS). There was a female predominance (84% and 60% in SAPS and PAPS, respectively). The prevalences of arterial (43%) and venous thrombosis (39%), fetal loss (40%), premature births (9%), anticardiolipin antibodies (88%) and lupus anticoagulant (54%) were similar in both groups. The prevalence of ANA-IFI, thrombocytopenia and autoimmune anemia was higher in SAPS.Patients with PAPS and SAPS did not present any differences in the clinical manifestations and immunological disorders of the syndrome. Those patients with SAPS were younger at the beginning of the disease and there was a female predominance. Our patients were different from those included in other Spanish published series, which could be explained by selection and classification bias.

Objective The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis, pregnancy loss, and thrombocytopenia associated with the production of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to investigate TF expression and procoagulant activity on monocytes from patients with primary APS and its correlation with thrombotic events. Methods Three groups of patients were studied: group 1 comprised 23 primary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with thrombosis but without antiphospholipid antibodies. Twenty age- and sex-matched healthy blood donors were used as controls (group 4). Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard methodology. Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TF(Ag)) and soluble TF(Ag) plasma levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF) on intact cells and cell lysates by a chromogenic assay. Levels of the cytokines that influence TF production, i.e., tumor necrosis factor alpha (TNF alpha) and interleukin-1beta (IL-1beta), were determined by ELISA. Results Cell surface expression of TF was increased in group 1 (mean +/- SEM 50.2 +/- 4% positive cells) compared with group 2 (14.6 +/- 1.6%), group 3 (16.8 +/- 3.7%), and group 4 (14.1 +/- 1.6%). TF(Ag) levels were also elevated in group 1 (215.8 +/- 11.2 pg/10(6)) compared with group 2 (150.8 +/- 15.2), group 3 (101.4 +/- 14.8), and group 4 (80.32 +/- 5.5). PCA-TF on intact cells and cell lysates was significantly increased in group 1 (148.8 +/- 16.3 units/10(5) lysate cells, compared with 54.5 +/- 11.5, 38.6 +/- 9.7, and 22.5 +/- 3.1 in groups 2, 3, and 4, respectively). Among group 1 patients, there was a significant increase in the degree of TF expression in those positive for IgG aCL, but not in those positive for IgM aCL or LAC. TNF alpha and IL-1beta plasma levels did not differ significantly between any of the groups. Conclusion These results suggest that monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.

The efficacy of interferon therapy in Caucasian children with chronic hepatitis B is similar to that in adults. However, little information is available about factors predicting response to this therapy in children. We have performed a univariate analysis to assess the strength of association between basal variables and response, and a multivariate analysis to determine the combination of basal variables which give the best prediction of response in terms of sensitivity and specificity.The basal parameters were studied in 50 children included in three different trials of interferon alpha therapy (360-700 MU/square meter of body surface, 2 or 3 times weekly for 12 to 24 weeks).Of these, 18 (36%) were responders. In the univariate analysis, a higher histological activity (p0.05), a lower percentage of HBcAg-stained hepatocytes (p0.001), aspartate amino transferase and alanine aminotransferase levels (p0.05) and alanine aminotransferase peak prior to serum HBV-DNA clearance (p0.05), were associated to the response. In the multivariate analysis, the combinations of the percentage of HBcAg stained cells with alanine aminotransferase levels and with the histological activity index were the best variables for predicting response (sensitivity: 100% and specificity: 89% and 86%, respectively).Factors predictive of response in children with chronic hepatitis B are similar to those found in adults, and may help in identifying those children with a better chance of responding.