Laboratory of Immunogenetics

Port-of-Spain, Trinidad and Tobago

Laboratory of Immunogenetics

Port-of-Spain, Trinidad and Tobago
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De Farias Santiago E.,Federal University of Pernambuco | De Farias Santiago E.,Laboratory of Immunopathology | De Oliveira S.A.,Laboratory of Immunopathology | De Oliveira Filho G.B.,Federal University of Pernambuco | And 13 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials. © 2014, American Society for Microbiology. All Rights Reserved.

Zinocker S.,University of Oslo | Zinocker S.,Laboratory of Immunogenetics | Vaage J.T.,University of Oslo
Frontiers in Immunology | Year: 2012

Mesenchymal stromal cells (MSC) have important immunomodulatory properties, they inhibit T lymphocyte allo-activation and have been used to treat graft-versus-host disease. How MSC exert their immunosuppressive functions is not completely understood but species specific mechanisms have been implicated. In this study we have investigated the mechanisms for rat MSC mediated inhibition ofT lymphocyte proliferation and secretion of inflammatory cytokines in response to allogeneic and mitogenic stimuli in vitro. MSC inhibited the proliferation of T cells in allogeneic mixed lymphocyte reactions and in response to mitogen with similar efficacy. The anti-proliferative effect was mediated by the induced expression of nitric oxide (NO) synthase and production of NO by MSC. This pathway was required and sufficient to fully suppress lymphocyte proliferation and depended on proximity of MSC and target cells. Expression of inducible NO synthase by MSC was induced through synergistic stimulation with tumor necrosis factor α and interferon γ secreted by activated lymphocytes. Conversely, MSC had a pronounced inhibitory effect on the secretion of these cytokines by T cells which did not depend on NO synthase activity or cell contact, but was partially reversed by addition of the cyclooxygenase (COX) inhibitor indomethacin. In conclusion, rat MSC use different mechanisms to inhibit proliferative and inflammatory responses of activated T cells. While proliferation is suppressed by production of NO, cytokine secretion appears to be impaired at least in part by COX-dependent production of prostaglandin E2. © 2012.

PubMed | Ospedale Generale, Laboratory of Immunogenetics and Rheumatology Unit
Type: Journal Article | Journal: Journal of medical case reports | Year: 2016

Silicone implants have been successfully used for breast augmentation and reconstruction in millions of women worldwide. The reaction to the silicone implant is highly variable; it can lead to local inflammatory symptoms, and sometimes to systemic symptoms and disease. Over 80 cases of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma have been reported in patients with silicone breast implants and have been accepted as a new clinical entity. To the best of our knowledge, an intravascular large B-cell lymphoma associated with a silicone breast implant has not been reported previously.A 48-year-old Caucasian woman who presented with high fever was found to have splenomegaly on physical examination. A laboratory diagnosis revealed pancytopenia, hypertriglyceridemia, and hyperferritinemia. She developed signs of altered sensorium, hemiparesis, aphasia, and cauda equina syndrome. On further evaluation, she fulfilled the necessary five out of eight criteria for diagnosis of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Dexamethasone administration was followed by prompt improvement; however, 3 days later she again manifested high fever, which persisted despite administration of immunoglobulin and cyclosporine A. Her silicone breast implant was considered a possible contributor to her macrophage activation syndrome and was therefore removed. A histological examination of the capsule tissue showed an extensive lymphohistiocytic/giant cell foreign body reaction suggestive of autoimmune/inflammatory syndrome induced by adjuvants. However, the histological examination unexpectedly also revealed an intravascular large B-cell lymphoma.The genetic background of our patient with silicone breast implants might have predisposed her to three rare and difficult to diagnose syndromes/diseases: macrophage activation syndrome/hemophagocytic lymphohistiocytosis, autoimmune/inflammatory syndrome induced by adjuvants, and intravascular large B-cell lymphoma. The simultaneous manifestation of all three syndromes suggests causal interrelationships. Human leukocyte antigen testing in all women who undergo silicon breast implantation could in the future enable us to better evaluate the risk of potential side effects.

Verweij S.P.,Laboratory of Immunogenetics | Catsburg A.,VU University Amsterdam | Ouburg S.,Laboratory of Immunogenetics | Lombardi A.,University of Milan | And 5 more authors.
Clinical Microbiology and Infection | Year: 2011

The management of the ongoing lymphogranuloma venereum epidemic in industrialized Western countries caused by Chlamydia trachomatis variant L2b still needs improvements in diagnosis, therapy and prevention. We therefore developed the first rapid C. trachomatis variant L2b-specific polymerase chain reaction to circumvent laborious ompA gene sequencing. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Cecati M.,Marche Polytechnic University | Emanuelli M.,Marche Polytechnic University | Giannubilo S.R.,Marche Polytechnic University | Quarona V.,Laboratory of Immunogenetics | And 4 more authors.
Journal of Biological Regulators and Homeostatic Agents | Year: 2013

The interactions taking place between mother and embryo have been the focus of detailed studies in recent years, where pregnancy is considered as an in vivo transplant. The immune systems of the mother and the embryo together establish a condition of tolerance, which lasts throughout the pregnancy. Alongside immunogenetic components, a contribution is provided by the ectoenzyme network, a chain of surface molecules mainly operating in closed environments and potentially providing inhibitory or activator signals. One of the soluble products of the ectoenzyme network with immunosuppressory potential is adenosine, a purine nucleoside that plays multiple roles in almost all tissues and organs. The hypothesis behind the work was studied in patients with recurrent pregnancy loss (RPL), an event which remains unexplained in over 50% of cases. To this aim, we analyzed the expression of CD39 (ectonucleoside triphosphate diphosphohydrolase 1, ENTPD1) and CD73 (ecto-5′-nucleotidase, NT5E), the main pathway for adenosine generation, in samples obtained from women with RPL. The study included the evaluation of the expression of TNF-α (a pro-inflammatory cytokine) and of an alternative pathway of adenosine generation run by CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) and PC-1 (ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1). The results of this study highlight the existence of a network of surface enzymes expressed at the maternal/fetal interface and addressed to the production of adenosine. Perturbation of this network may induce a rescue pathway driven by CD38 and ENPP1. Ectoenzyme and inflammation may be considered now key elements in orchestrating the events leading to the interruption of pregnancy in the RPL sample analyzed and at the same potentially becoming therapeutic targets. Copyright © by BIOLIFE, s.a.s.

Joyce M.G.,University of Leicester | Joyce M.G.,Laboratory of Immunogenetics | Ekanem I.S.,University of Manchester | Roitel O.,University of Leicester | And 7 more authors.
FEBS Journal | Year: 2012

We report the crystal structure of the FAD/NADPH-binding domain (FAD domain) of the biotechnologically important Bacillus megaterium flavocytochrome P450 BM3, the last domain of the enzyme to be structurally resolved. The structure was solved in both the absence and presence of the ligand NADP +, identifying important protein interactions with the NADPH 2'-phosphate that helps to dictate specificity for NADPH over NADH, and involving residues Tyr974, Arg966, Lys972 and Ser965. The Trp1046 side chain shields the FAD isoalloxazine ring from NADPH, and motion of this residue is required to enable NADPH-dependent FAD reduction. Multiple binding interactions stabilize the FAD cofactor, including aromatic stacking with the adenine group from the side chains of Tyr860 and Trp854, and several interactions with FAD pyrophosphate oxygens, including bonding to tyrosines 828, 829 and 860. Mutagenesis of C773 and C999 to alanine was required for successful crystallization, with C773A predicted to disfavour intramolecular and intermolecular disulfide bonding. Multiangle laser light scattering analysis showed wild-type FAD domain to be near-exclusively dimeric, with dimer disruption achieved on treatment with the reducing agent dithiothreitol. By contrast, light scattering showed that the C773A/C999A FAD domain was monomeric. The C773A/C999A FAD domain structure confirms that Ala773 is surface exposed and in close proximity to Cys810, with this region of the enzyme's connecting domain (that links the FAD domain to the FMN-binding domain in P450 BM3) located at a crystal contact interface between FAD domains. The FAD domain crystal structure enables molecular modelling of its interactions with its cognate FMN (flavodoxin-like) domain within the BM3 reductase module. © 2012 FEBS.

Jalel A.,Research Unit on the Antioxidant Compounds | Ridha A.,Research Unit on the Antioxidant Compounds | Laurent D.,Hospital Foschi | Philippe M.,Laboratory of Immunogenetics | Hamdaoui M.,Research Unit on the Antioxidant Compounds
Indian Journal of Dermatology | Year: 2010

Background: The human leukocyte antigen (HLA) system in the skin coordinates the pigmentation and immune response and could be implicated in the pathogenesis of vitiligo. Human leukocyte antigen HLA-G is a nonclassic, major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface. It is known to protect the fetus from maternal cellular immunity. Analogically, it could be implicated in the pathogenesis of autoimmune diseases such as vitiligo. Aims: To compare the expression of HLA-G between vitiligo patients and healthy controls. Materials and Methods: In the present study, 22 vitiligo patients and 24 healthy controls were investigated to look for a possible correlation between HLA-G expression and this pathology. Expression of HLA-G in cutaneous biopsy specimens was investigated by immunohistochemical analysis. Results: HLA-G was detected in the biopsy specimens of 3 (13%) out of 22 patients. This number was significantly higher in healthy controls 18 (75%) out of 24 as compared to vitiligo patients ( P < 0.001). Conclusion: There is significant negative correlation between HLA-G expression and vitiligo. In our mind, upregulation of HLA-G expression in lesional skin could be local (superficial expression) or systemic (soluble HLA-G isoforms) compensation to restore normal pigmentation in lesions.

Murakami Y.,Laboratory of Immunogenetics
Clinical calcium | Year: 2010

Cytokines have an essential role for cell-cell communication. They can regulate cell proliferation, differentiation, survival, and function. Interaction of cell surface receptor with cytokines is necessary for control of physiological responses. Activation of cytokine receptors transduces specific signal in the receptor-expressing cells, resulting that cytokines can regulate specific cell population. Thus, cytokines contribute directly or indirectly to morphogenesis, host defense and immune response, play critical roles for homeostasis and development.

Andreani M.,Laboratory of Immunogenetics | Testi M.,Laboratory of Immunogenetics | Battarra M.,Laboratory of Immunogenetics | Lucarelli G.,University of Rome Tor Vergata
Chimerism | Year: 2011

Previous studies have shown that a stable presence of both donor and recipient haematopoietic derived cells after allogeneic haematopoietic stem cell transplantation (HSCT) occurs in approximately ten percent of the patients affected by b-Thalassemia. Once achieved this condition, defined as persistent mixed chimerism (PMC), the patients do not require additional red blood cells (RBCs) support and, regardless of the presence in some cases of an extremely low percentage of donor-derived nucleated cells, they are clinically cured by an incomplete, but functional graft. Most of the published papers have, however, investigated the impact of donor engraftment in the nucleated cells rather than in the mature erythrocytes. We have recently published a paper showing that in four long-term transplanted patients affected by hemoglobinopathies, characterized by the presence of few donor engrafted nucleated cells-both in the peripheral blood and in the bone marrow-the majority of the erythrocytes were of donor origin. Moreover we showed that the proportion of donor-derived erythroid precursors, determined by analyzing singularly picked-up burst-forming unit erythroid colonies, was equivalent to that observed in the mature nucleated cells rather than in the red blood cells. These results suggest that in patients characterized by the presence of PMC after HSCT a selective advantage of the donor erythroid precursors maturation might successfully contrast the problems bound to the recipient ineffective erythropoiesis. When genetically modified HSCT will be a possible option for treating Thalassemia Major, the co-existence of the repaired cells with those still expressing the genetic defect will be an expected scenario, not in an allogeneic, but in an autologous environment. © 2011 Landes Bioscience.

Oliveira A.C.,Masters Program in Health science | Mattos L.C.,Laboratory of Immunogenetics | Cavasini C.E.,Center for Investigation of Microorganisms
Journal of Venomous Animals and Toxins Including Tropical Diseases | Year: 2011

Dufy gene (FY) codifes the transmembrane glycoprotein Dufy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Dufy histo-blood system which were designated receptors for chemokines and denominated DARC (Dufy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing infammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an infammatory disease, in which infltrated infammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profle of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this infammatory disease.

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