http://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2012, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/cdi/2012/480429/Despite advances in conventional treatment modalities for malignant brain tumors—surgery, radiotherapy, and chemotherapy—the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages.Vidyalakshmi Chandramohan, John H. Sampson, Ira Pastan, and Darell D. BignerCopyright © 2012 Vidyalakshmi Chandramohan et al. All rights reserved.http://www.hindawi.com/journals/cdi/2012/931952/The recent demonstration that immunotherapeutic approaches may be clinically effective for cancer patients has renewed the interest for this strategy of intervention. In particular, clinical trials using adoptive T-cell therapies disclosed encouraging results, particularly in the context of Epstein-Barr-virus- (EBV-) related tumors. Nevertheless, the rate of complete clinical responses is still limited, thus stimulating the development of more effective therapeutic protocols. Considering the relevance of innate immunity in controlling both infections and cancers, innovative immunotherapeutic approaches should take into account also this compartment to improve clinical efficacy. Evidence accumulated so far indicates that innate immunity effectors, particularly NK cells, can be exploited with therapeutic purposes and new targets have been recently identified. We herein review the complex interactions between EBV and innate immunity and summarize the therapeutic strategies involving both adaptive and innate immune system, in the light of a fruitful integration between these immunotherapeutic modalities for a better control of EBV-driven tumors.Debora Martorelli, Elena Muraro, Anna Merlo, Riccardo Turrini, Damiana Antonia Faè, Antonio Rosato, and Riccardo DolcettiCopyright © 2012 Debora Martorelli et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/718708/S. aureus represents a critical cofactor in atopic dermatitis (AD). In this paper, the prevalence of S. aureus infection/colonization was evaluated in 117 children as well as in their cohabitants, in order to assess the value of S. aureus characterization in predicting disease onset and severity and in providing indications for prophylaxis. Results showed that children with AD as well as their cohabitants had a significantly greater incidence of S. aureus infection/colonization as compared to controls. The genetic characterization showed a virtual identity of the bacteria strains collected at different sites of the patients with those found in the cohabitants, suggesting both a direct transmission between the nasal reservoir and the lesions in the same atopic subject and a risk for reinfection within family cohabitants. These data stress the need of preliminary laboratory assessment and posttherapy control in both AD patients and their close contacts for effective S. aureus eradication.Chiara Pascolini, JoLinda Sinagra, Simone Pecetta, Valentina Bordignon, Alessandra De Santis, Laura Cilli, Viviana Cafiso, Grazia Prignano, Bruno Capitanio, Claudio Passariello, Stefania Stefani, Paola Cordiali-Fei, and Fabrizio EnsoliCopyright © 2011 Chiara Pascolini et al. All rights reserved.http://www.hindawi.com/journals/cdi/2012/785825/The human papillomavirus (HPV) directly infects cervical keratinocytes and interferes with TLR signalling. To shed light on the effect of HPV on upstream receptors, we evaluated TLRs 1–9 gene expression in HPV-negative normal and HPV-positive pre-malignant and malignant ex vivo cervical tissue. Quantitative real-time polymerase chain reaction was performed separately for epithelial and stromal tissue compartments. Differences in gene expression were analyzed by the Jonckheere-Terpstra trend test or the Student's t-test for pairwise comparison. Laser capture microdissection revealed an increase in TLR3 and a decrease in TLR1 mRNA levels in dysplastic and carcinoma epithelium, respectively. In the stroma, a trend of increasing TLR 1, 2, 5, 6, and 9 mRNA levels with disease severity was found. These findings implicate the involvement of TLR3 and TLR1 in early and late cervical carcinogenesis, respectively, suggesting that stromal upregulation of TLRs may play a role in cervical disease progression.Correne A. DeCarlo, Bruce Rosa, Robert Jackson, Sarah Niccoli, Nicholas G. Escott, and Ingeborg ZehbeCopyright © 2012 Correne A. DeCarlo et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/302739/Allergic rhinitis (AR) is a public health problem with high prevalence worldwide. We evaluated levels of specific IgE, IgA, and IgG4 antibodies to the Dermatophagoides pteronyssinus (Dpt) house dust mite and to its major allergens (Der p1 and Der p2) in serum and saliva samples from allergic and nonallergic children. A total of 86 children were analyzed, from which 72 had AR and 14 were nonallergic healthy children. Serum IgE and serum/salivary IgG4 levels to Dpt, Der p1, and Der p2 were higher in allergic children whereas serum/salivary IgA levels to all allergens were higher in nonallergic children. IgE levels positively correlated with IgG4 and IgA to all allergens in allergic children, while IgA levels negatively correlated with IgG4 to Dpt and Der p1 in nonallergic children. In conclusion, mite-specific IgA antibodies predominate in the serum and saliva of nonallergic children whereas mite-specific IgE and IgG4 are prevalent in allergic children. The presence of specific IgA appears to have a key role for the healthy immune response to mucosal allergens. Also, specific IgA measurements in serum and/or saliva may be useful for monitoring activation of tolerance-inducing mechanisms during allergen specific immunotherapeutic procedures, especially sublingual immunotherapy.Diego O. Miranda, Deise A. O. Silva, Jorge F. C. Fernandes, Meimei G. J. Queirós, Hamilton F. Chiba, Leandro H. Ynoue, Rafael O. Resende, Janethe D. O. Pena, Sun-Sang J. Sung, Gesmar R. S. Segundo, and Ernesto A. TaketomiCopyright © 2011 Diego O. Miranda et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/481948/Background. We have shown that approximately 30% of human peripheral blood B-cells express CD25. B cells expressing CD25 display a mature phenotype belonging to the memory B-cell population and have a better proliferative and antigen-presenting capacity. The aim of the present study was to characterize the CD25-expressing subset of B cells in human cord blood. Material and Methods. Mononuclear cell fraction from human cord blood (n=34) and peripheral adult blood (n=22) was sorted into CD20+CD25+ and CD20+CD25- B-cell populations. Phenotype and function of these B-cell populations were compared using flow cytometry, proliferation, cytokine production, and immunoglobulin secretion. Results. CD25-expressing B cells are a limited population of cord blood mononuclear cells representing 5% of the CD20+ B cells. They are characterised by high expression of CD5 in cord blood and CD27 in adult blood. CD25-expressing B cells express a functional IL-2 receptor and high levels of CC-chemokine receptors and spontaneously produce antibodies of IgG and IgM subclass. Conclusions. CD25 expression is a common denominator of a specific immunomodulatory B-cell subset ready to proliferate upon IL-2 stimulation, possibly ready to migrate and home into the peripheral tissue for further differentiation/action.Sylvie Amu and Mikael BrisslertCopyright © 2011 Sylvie Amu and Mikael Brisslert. All rights reserved.http://www.hindawi.com/journals/cdi/2011/807483/Studies showed that specific probiotics provide therapeutic benefits in inflammatory bowel disease. In vitro evidence suggested that Lactobacillus paracasei also called ST11 (CNCM I-2116) is a potent strain with immune modulation properties. However, little is known about its capacity to alleviate inflammatory symptoms in vivo In this context, the main objective of this study was to investigate the role of ST11 on intestinal inflammation using the adoptive transfer mouse model of experimental colitis. Rag2-/- recipient mice were fed with ST11 (109 CFU/day)a month prior toinduce colitis by adoptive transfer of naive T cells. One month later, in clear contrast to nonfed mice, weight loss was significantly reduced by 50% in ST11-fed mice. Further analysis of colon specimens revealed a significant reduction neutrophil infiltration and mucosal expression of IL1β, IL-6, and IL12 proinflammatory cytokines, whereas no consistent differences in expression of antibacterial peptides or tight junction proteins were observed between PBS and ST11-fed mice. All together, our results demonstrate that oral administration of ST11 was safe and had a significant preventive effect on colitis. We conclude that probiotics such as Lactobacillus paracasei harbor worthwhile in vivo immunomodulatory properties to prevent intestinal inflammation by nutritional approaches.Manuel Oliveira, Nabil Bosco, Genevieve Perruisseau, Jeanne Nicolas, Iris Segura-Roggero, Stéphane Duboux, Muriel Briand, Stéphanie Blum, and Jalil BenyacoubCopyright © 2011 Manuel Oliveira et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/352686/Objectives. To evaluate lipid profile changes after anti-TNF therapy in patients with psoriatic arthritis (PsA). Methods. Fifteen PsA patients (eight polyarticular, four oligoarticular, two axial, and one mutilating) under infliximab were included. None had dyslipoproteinemia or previous statin use. Total cholesterol (TC) and its fractions, inflammatory markers, and prednisone use were evaluated. Results. The comparisons of lipid levels between baseline and after three months (3M) of anti-TNF therapy showed that there was a significant increase in mean triglycerides (117.8±49.7 versus 140.1±64.1 mg/dL, P=0.028) and VLDL-c (23.6±10.5 versus 28.4±13.7 mg/dL, P=0.019) levels. In contrast, there were no differences in the mean TC (P=0.28), LDL-c (P=0.42), and HDL-c (P=0.26) levels. Analysis of the frequencies of each lipid alteration at baseline and at 3M were alike (P>0.05). Positive correlations were found between VLDL-c and CRP (r=0.647, P=0.009) and between triglycerides and CRP (r=0.604, P=0.017) levels at 3M. ESR reduction was observed after 3M (P=0.04). Mean prednisone dose remained stable at beginning and at 3M (P=0.37). Conclusion. This study demonstrated that anti-TNF may increase TG and VLDL-c levels in PsA patients after three months.Karla R. Castro, Nádia E. Aikawa, Carla Gonçalves Saad, Júlio C. B. Moraes, Ana C. Medeiros, Licia Maria H. Mota, Clovis A. A. Silva, Eloísa Bonfá, and Jozélio F. CarvalhoCopyright © 2011 Karla R. Castro et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/730828/Glucocorticoid administration before cardiopulmonary bypass (CPB) can reduce the systemic inflammatory response and improve clinical outcome. Long pentraxin PTX3 is a novel inflammatory parameter that could play a protective cardiovascular role by regulating inflammation. Twenty-nine children undergoing open heart surgery were enrolled in the study. Fourteen received dexamethasone (1st dose 1.5 mg/Kg i.v. or i.m. the evening before surgery; 2nd dose 1.5 mg/kg i.v. before starting bypass) and fifteen children served as control. Blood PTX3, short pentraxin C-reactive protein (CRP), interleukin-1 receptor II (IL-1RII), fibrinogen and partial thromboplastin time (PTT) were assayed at different times. PTX3 levels significantly increased during CPB in dexamethasone-treated (+D) and dexamethasone-untreated (−D) subjects, but were significantly higher in +D than −D patients. CRP levels significantly increased both in +D and −D patients in the postoperative days, with values significantly higher in −D than +D patients. Fibrinogen and PTT values were significantly higher in −D than +D patients in the 1st postoperative day. IL-1RII plasma levels increased in the postoperative period in both groups. Dexamethasone prophylaxis in pediatric patients undergoing CPB for cardiac surgery is associated with a significant increase of blood PTX3 that could contribute to decreasing inflammatory parameters and improving patient clinical outcome.Franco Lerzo, Giuseppe Peri, Andrea Doni, Paola Bocca, Fabio Morandi, Angela Pistorio, Anna Maria Carleo, Alberto Mantovani, Vito Pistoia, and Ignazia PrigioneCopyright © 2011 Franco Lerzo et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/915864/Thymectomy is performed in infants during cardiothoracic surgery leaving many patients with reduced thympopoiesis. An association between immune disorders and regulatory T cells (Treg) after incidental thymectomy has not been investigated. Questionnaires soliciting symptoms of atopic or autoimmune disease and biomarkers were measured in children and adults with congenital heart disease and either reduced or preserved thymopoiesis. Tregs were examined. Atopic or autoimmune-like symptoms and elevated anti-dsDNA antibodies were common after surgery in individuals with low thymopoiesis. Total Treg number and function were maintained but with fewer naïve Treg. TCR spectratypes were similar to other memory T cells. These data suggest that thymectomy does not reduce total Treg number but homeostasis is affected with reduced naïve Treg. Prevalence of autoimmune or atopic symptoms after surgery is not associated with total number or proportion of Tregs but appears to be due to otherwise unknown factors that may include altered Treg homeostasis.Nancy J. Halnon, Paige Cooper, Diana Yu Hui Chen, M. Ines Boechat, and Christel H. UittenbogaartCopyright © 2011 Nancy J. Halnon et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/291085/To determine the diagnostic utility of serum calprotectin, a mediator of innate immune response against infections, we performed a multicenter study involving newborns with a birth weight <1500 g and a postnatal age >72 hours of life. The diagnostic accuracy of serum calprotectin was compared with that of the most commonly used markers of neonatal sepsis (white blood cell count, immature-to-total-neutrophil ratio, platelet count, and C-reactive protein). We found that the serum calprotectin concentration was significantly higher (P<.001) in 62 newborns with confirmed sepsis (3.1±1.0  μg/mL) than in either 29 noninfected subjects (1.1±0.3 μg/ml) or 110 healthy controls (0.91±0.58 μg/ml). The diagnostic accuracy of serum calprotectin was greater (sensitivity 89%, specificity 96%) than that of the traditional markers of sepsis. In conclusion, serum calprotectin is an accurate marker of sepsis in very low birth weight newborns.Gianluca Terrin, Annalisa Passariello, Francesco Manguso, Gennaro Salvia, Luciano Rapacciuolo, Francesco Messina, Francesco Raimondi, and Roberto Berni CananiCopyright © 2011 Gianluca Terrin et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/428703/Common variable immunodeficiency (CVID) is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE) was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR) criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40 mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.A. A. Jesus, C. M. A. Jacob, C. A. Silva, M. Dorna, A. C. Pastorino, and M. Carneiro-SampaioCopyright © 2011 A. A. Jesus et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/917015/Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2 (PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production.Esther López, María Paz Zafra, Beatriz Sastre, Cristina Gámez, Mar Fernández-Nieto, Joaquín Sastre, Carlos Lahoz, Santiago Quirce, and Victoria Del PozoCopyright © 2011 Esther López et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/143517/Autoantibodies targeting the β1-adrenergic receptor (AAB-β1) display agonist-like effects, which may have a pathogenic role in the progression of heart failure. Here, we used the electrophysiological recordings to explore the effects of AAB-β1-positive serum from Chinese patients with heart failure on the activity of the peak transient outward potassium current (Ito) and the end 50 ms steady-state potassium current (Iss) in mouse cardiac myocytes. We found that the AAB-β1-positive serum had no effect on the activity of Ito, but it produced a decrease in the currents of Iss. A low concentration of positive serum (1/100) had a small inhibitory effect on Iss. However, positive serum at 1 : 10, 1 : 20, and 1 : 50 significantly decreased Iss. The concentration-dependence analysis showed that the EC50 of AAB-β1-positive serum was 1/60.24 and its nH was 2.86. It indicated that the AAB-β1 could inhibit Iss in mouse cardiomyocyte in a concentration-dependent manner.Yuan-yuan Wang, Zhi-Yong Ma, Xiao-Dong Li, Jian-chun Wang, Wei Zhang, Li Li, and Yun ZhangCopyright © 2011 Yuan-yuan Wang et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/579650/The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively (Helicobacter pylori infection, Salmonella infection, and inflammatory bowel disease). Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases.Georgina L. Hold, Indrani Mukhopadhya, and Tom P. MonieCopyright © 2011 Georgina L. Hold et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/920146/Cell division is closely related to telomerase activity (hTERT mRNA). Lower expression of lymphocitic hTERT mRNA may easily cause cell aging, which is not beneficial to maintaining a durable lymphocyte division. To date, there is no study to investigate IFNα therapy on hTERT mRNA expression in PBMCs of patients with chronic hepatitis B (CHB). We quantitatively detected hTERT mRNA from study subjects and made each hTERT mRNA normalized (NhTERT mRNA). Mean NhTERT mRNA level was lower in either CHB group, but it significantly increased in IFNα-treated group compared with CHB control group, and a longer duration of IFNα therapy could increase the level. Moreover, the mean NhTERT mRNA in subgroup with HBeAg loss was significantly higher than that in subgroup without. NhTERT mRNA was markedly correlated with CD3+ T lymphocyte count and CD4+/CD8+ ratio. The results showed that IFNα therapy could upregulate the expression of hTERT mRNA in PBMCs.Chuan-wu Zhu, Ming Chen, Xiang-rong Luo, Hai-yan Wang, Li-hua Wang, Jian-hong Wu, Ming Li, Xue-hua Zhang, Wei Zhu, Jian-zhong Ye, and Feng QianCopyright © 2011 Chuan-wu Zhu et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/283896/Laura Ridolfi, Massimiliano Petrini, Laura Fiammenghi, Anna Maria Granato, Valentina Ancarani, Elena Pancisi, Emanuela Scarpi, Massimo Guidoboni, Giuseppe Migliori, Stefano Sanna, Francesca Tauceri, Giorgio Maria Verdecchia, Angela Riccobon, Linda Valmorri, and Ruggero RidolfiCopyright © 2011 Laura Ridolfi et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/564062/Objective. Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model. Methods. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3−/− mice. Results. Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3+ cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8+ cells, whereas the expression of CXCR3 on CD3+ and CD8+ splenocytes decreased in PBC model. Compared with WT mice, CXCR3−/− mice developed delayed and milder progression of cellular inflammation. Conculsions. CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.Wen Zhang, Yunyun Fei, Jinming Gao, Bin Liu, and Fengchun ZhangCopyright © 2011 Wen Zhang et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/405310/Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a major health problem, with 10 million new cases diagnosed each year. Innate immunity plays an important role in the host defense against M. tuberculosis, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of M. tuberculosis, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Among the TLR family, TLR2, TLR4, and TLR9 and their adaptor molecule MyD88 play the most prominent roles in the initiation of the immune response against tuberculosis. In addition to TLRs, other PRRs such as NOD2, Dectin-1, Mannose receptor, and DC-SIGN are also involved in the recognition of M. tuberculosis. Human epidemiological studies revealed that genetic variation in genes encoding for PRRs and downstream signaling products influence disease susceptibility, severity, and outcome. More insight into PRRs and the recognition of mycobacteria, combined with immunogenetic studies in TB patients, does not only lead to a better understanding of the pathogenesis of tuberculosis but also may contribute to the design of novel immunotherapeutic strategies.Johanneke Kleinnijenhuis, Marije Oosting, Leo A. B. Joosten, Mihai G. Netea, and Reinout Van CrevelCopyright © 2011 Johanneke Kleinnijenhuis et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/248243/The relationship between prolactin (PRL) and the immune system has been demonstrated in the last two decades and has opened new windows in the field of immunoendocrinology. However, there are scarce reports about PRL in primary antiphospholipid syndrome (pAPS). The objective of this study was to evaluate PRL levels in patients with pAPS compared to healthy controls and to investigate their possible clinical associations. Fifty-five pAPS patients according to Sapporo criteria were age- and sex-matched with 41 healthy subjects. Individuals with secondary causes of hyperprolactinemia (HPRL) were excluded; demographic, biometric, and clinical data, PRL levels, antiphospholipid antibodies, inflammatory markers, and other routine laboratory findings were analyzed. PRL levels were similar between pAPS and healthy controls (8.94±7.02 versus 8.71±6.73 ng/mL, P=.876). Nine percent of the pAPS patients and 12.1% of the control subjects presented HPRL (P=.740). Comparison between the pAPS patients with hyper- and normoprolactinemia revealed no significant differences related to anthropometrics, clinical manifestations, medications, smoking, and antiphospholipid antibodies (P>.05). This study showed that HPRL does not seem to play a role in clinical manifestations of the pAPS, differently from other autoimmune rheumatic diseases.Manoel Tavares Neves Junior, Carlos Ewerton Maia Rodrigues, and Jozelio Freire de CarvalhoCopyright © 2011 Manoel Tavares Neves Junior et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/843763/Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF) patients. Sensitization to A. fumigatus is common in both atopic asthmatic and CF patients, yet only 1-2% of asthmatic and 7–9% of CF patients develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response is characterized by Th2 responses to Aspergillus allergens, increased serum IgE and eosinophilia. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA) polymorphisms, IL-10-1082GA promoter polymorphisms, surfactant protein A2 (SP-A2) polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. The studies indicate that ABPA patients are genetically at risk to develop skewed and heightened Th2 responses to A. fumigatus antigens. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4 and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA.Alan P. Knutsen and Raymond G. SlavinCopyright © 2011 Alan P. Knutsen and Raymond G. Slavin. All rights reserved.http://www.hindawi.com/journals/cdi/2011/516219/We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.Narcís Saubi, Eung-Jun Im, Raquel Fernández-Lloris, Olga Gil, Pere-Joan Cardona, Josep Maria Gatell, Tomáš Hanke, and Joan JosephCopyright © 2011 Narcís Saubi et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/404929/Objective. Our aim was to investigate the effects of IL-6 blockade on the progression of Mycobacterium tuberculosis (TB) and compare them with those of TNF-α blockade in mice. Methods. Mice were intravenously infected with TB and injected with antibodies. Survival was monitored and histological and immunological studies were carried out. Results. All anti-IL-6R Ab-treated mice and 8 of 10 control mice survived until sacrificed 224 days after TB challenge, whereas anti-TNF-α Ab-treated mice all died between 120 and 181 days. Anti-IL-6R Ab-treated mice exhibited no significant differences in TB CFU in organs, including the lungs, and no deterioration in histopathology compared to control mice at 4 weeks. In contrast, anti-TNF-α Ab-treated mice exhibited increased TB CFU and greater progression of histopathological findings in organs than control mice. Spleen cells from anti-TNF-α Ab-treated mice had decreased antigen-specific response in IFN-γ release and proliferation assays. The results in anti-IL-6R Ab-treated mice suggest that spleen cell responses were decreased to a lesser degree. Similar results were obtained in IL-6 knockout (KO) mice, compared with TNF receptor 1 (TNFR1) KO and TNFR1/IL-6 double KO (DKO) mice. Conclusion. IL-6R blockade promotes the progression of TB infection in mice far less than TNF-α blockade.Masaji Okada, Yoko Kita, Noriko Kanamaru, Satomi Hashimoto, Yasushi Uchiyama, Masahiko Mihara, Yoshikazu Inoue, Yoshiyuki Ohsugi, Tadamitsu Kishimoto, and Mitsunori SakataniCopyright © 2011 Masaji Okada et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/370872/Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.J. E. Z. Castro, I. Vado-Solis, C. Perez-Osorio, and T. M. FredekingCopyright © 2011 J. E. Z. Castro et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/316314/Altered natural killer (NK) cell function is a component of the global immune dysregulation that occurs in advanced malignancies. Another condition associated with altered NK homeostasis is normal pregnancy, where robust infiltration with CD16− CD9+ NK cells can be identified in decidual tissues, along with a concomitant expansion of CD16− NK cells in the maternal peripheral blood. In metastatic melanoma, we identified a similar expansion of peripheral blood CD16− NK cells (median 7.4% in 41 patients with melanoma compared with 3.0% in 29 controls, P<.001). A subset of NK cells in melanoma patients also expresses CD9, which is characteristically expressed only on NK cells within the female reproductive tract. Expansion of CD16− NK cells was associated with elevated plasma transforming growth factor-beta (TGF-β levels (median 20 ng/ml, Spearman's ρ=0.81,P=.015)). These findings suggest the possibility of exploring anti-TGF-β therapy to restore NK function in melanoma.Shernan G. Holtan, Douglas J. Creedon, Michael A. Thompson, Wendy K. Nevala, and Svetomir N. MarkovicCopyright © 2011 Shernan G. Holtan et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/305656/Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.Mie Oki, Norihiko Watanabe, Takayoshi Owada, Yoshihiro Oya, Kei Ikeda, Yasushi Saito, Ryutaro Matsumura, Yohei Seto, Itsuo Iwamoto, and Hiroshi NakajimaCopyright © 2011 Mie Oki et al. All rights reserved.http://www.hindawi.com/journals/cdi/2010/327417/Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may modulate progression of the disease and expression of bone proresorptive cytokines. IL-12 is a potent inducer of IFN-γ production, which stimulates Th1 effector cells. Many evidences have shown a positive correlation between the bone resorptive cytokine IL-1β and the production of IL-12 and IFN-γ. Furthermore, IL-12 may have a potential role in the release of bone resorptive mediators and blockade of Th2 cytokines, affecting the progression of periapical bone loss. Nevertheless, IL-12 and IFN-γ have also been described as suppressors of osteoclast differentiation and activation, favoring bone maintenance. This paper focuses on the controversial roles of IL-12 in periapical lesions.Celso Martins Queiroz-Junior, Marcelo José Barbosa Silva, Jôice Dias Corrêa, Mila Fernandes Moreira Madeira, Thiago Pompermaier Garlet, Gustavo Pompermaier Garlet, Fernando Queiroz Cunha, Mauro Martins Teixeira, and Tarcília Aparecida da SilvaCopyright © 2010 Celso Martins Queiroz-Junior et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/390726/Background. Given that clinical evaluation may underestimate the joint damage and that early treatment can slow down psoriatic arthritis (PsA) progression, screening psoriasis patients with imaging tools that can depict early PsA changes would entail clear benefits. Objective. To compare the ability of X-ray and ultrasound (US) examination in detecting morphological abnormalities consistent with early PsA in patients with psoriasis, using rheumatological evaluation as the gold standard for diagnosis. Methods. Patients with chronic plaque psoriasis and no previous PsA diagnosis attending our outpatient dermatology clinic and reporting finger/toe joint and/or tendon pain underwent X-ray and US evaluation; they were subsequently referred to a rheumatologist for clinical examination and review of imaging findings. Results. Abnormal US and/or X-ray findings involving at least one finger and/or toe (joints and/or tendons) were seen in 36/52 patients: 11 had one or more X-ray abnormalities, including erosion, joint space narrowing, new bone formation, periarticular soft tissue swelling, and periarticular osteoporosis; 36 had suspicious changes on US. Conclusion. US proved valuable in detecting joint and/or tendon abnormalities in the fingers and toes of patients with suspicious changes. The dermatologist should consider US to obtain an accurate assessment of suspicious findings.Clara De simone, Giacomo Caldarola, Magda D'Agostino, Angelo Carbone, Cristina Guerriero, Lorenzo Bonomo, Pierluigi Amerio, and Nicola MagarelliCopyright © 2011 Clara De simone et al. All rights reserved.http://www.hindawi.com/journals/cdi/2011/470803/Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.Mototsugu Tanaka, George Seki, Tomonosuke Someya, Michio Nagata, and Toshiro FujitaCopyright © 2011 Mototsugu Tanaka et al. All rights reserved.http://www.hindawi.com/journals/cdi/2010/567571/There is increasing interest in understanding the mechanisms underlying the interactions that occur between Mycobacterium tuberculosis and host innate immune cells. These cells express pattern recognition receptors (PRRs) which recognise mycobacterial pathogen-associated molecular patterns (PAMPs) and which can influence the host immune response to the infection. Although many of the PRRs appear to be redundant in the control of M. tuberculosis infection in vivo, recent discoveries have revealed a key, nonredundant, role of the Syk/CARD9 signalling pathway in antimycobacterial immunity. Here we review these discoveries, as well as recent data investigating the role of the Syk/CARD9-coupled PRRs that have been implicated in mycobacterial recognition, including Dectin-1 and Mincle.Mohlopheni Jackson Marakalala, Lisa M. Graham, and Gordon D. BrownCopyright © 2010 Mohlopheni Jackson Marakalala et al. All rights reserved.