scholarly journals Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8

2021 ◽  
Vol 15 (9) ◽  
pp. e0009795
Author(s):  
Tirza Gabrielle Ramos de Mesquita ◽  
José do Espírito Santo Junior ◽  
Thais Carneiro de Lacerda ◽  
Krys Layane Guimarães Duarte Queiroz ◽  
Cláudio Marcello da Silveira Júnior ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Wide Spectrum ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Cellular Functions ◽  
Pcr Rflp ◽  
Plasma Cytokines ◽  
Polymerase Chain ◽  
Leishmania Guyanensis ◽  
Necrosis Factor

Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadjage/sex = 1.3 [95%CI 0.9–1.8]; Padjage/sex 0.14) compared to individuals with the genotype GG (ORadjage/sex = 0.77 [95%CI 0.56–1.0]; Padjage/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadjage/sex = 0.77 [95%CI 0.5–1.1]; Padjage/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (ORadjage = 1.3 [95% CI = 0.9–2.0]; Padjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0–1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadjage = 1.4 [1.1–1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadjage/sex = 2.0 [95%CI 0.83–5.0]; Padjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0–4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.

scholarly journals TREM1 rs2234237 (Thr25Ser) Polymorphism in Patients with Cutaneous Leishmaniasis Caused by Leishmania guyanensis: A Case-Control Study in the State of Amazonas, Brazil

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 498
Author(s):  
José do Espírito Santo Júnior ◽  
Tirza Gabrielle Ramos de Mesquita ◽  
Luan Diego Oliveira da Silva ◽  
Felipe Jules de Araújo ◽  
Josué Lacerda de Souza ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Fragment Length Polymorphism ◽  
P Value ◽  
Tnf Α ◽  
Plasma Cytokines ◽  
Polymerase Chain ◽  
Leishmania Guyanensis ◽  
Control Study ◽  
Leishmania Parasites ◽  
Modest Effect

Background: Leishmaniasis is an infectious disease caused by Leishmania parasites. A Th1 immune response is necessary in the acute phase to control the pathogen. The triggering receptor expressed on myeloid cells (TREM)-1 is a potent amplifier of inflammation. Our aim is to identify whether the TREM1 variant rs2234237 A/T (Thr25Ser) is associated with the disease development of cutaneous leishmaniasis (CL) in Leishmania guyanensis-infected individuals. The effects of the rs2234237 genotypes on plasma cytokines IL-1β, IL-6, IL-8, IL-10, MCP-1 and TNF-α are also investigated. Methods: 838 patients with CL and 818 healthy controls (HCs) living in the same endemic areas were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Plasma cytokines were assayed in 400 patients with CL and 400 HCs using the BioPlex assay. Results: The genotypes’ and alleles’ frequencies were similar in both patients with CL (AA = 618, 74%; AT = 202, 24%; TT = 18, 2%) and in HCs (AA = 580, 71%; AT = 220, 27%; TT = 18, 2%). Rs2234237 showed a modest effect on plasma IL-10 that disappeared when correction of the p-value was applied. Plasma IL-10 by rs2234237 genotypes were (mean ± SEM; AA = 2.91 pg/mL ± 0.14; AT = 2.35 pg/mL ± 0.12; TT = 3.14 pg/mL ± 0.56; p = 0.05). Conclusion: The TREM1 rs2234237 (Thr25Ser) seems to have no influence on the susceptibility or resistance to L. guyanensis infections.

scholarly journals Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade

2005 ◽  
Vol 201 (9) ◽  
pp. 1479-1486 ◽  
Author(s):  
Virginia Pascual ◽  
Florence Allantaz ◽  
Edsel Arce ◽  
Marilynn Punaro ◽  
Jacques Banchereau
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Joint Involvement ◽  
Peripheral Blood Mononuclear ◽  
Immunity Genes ◽  
Systemic Onset ◽  
Necrosis Factor

Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses ∼10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1β. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.

Molecular epidemiology and clinical manifestations of human cryptosporidiosis in Sweden

2012 ◽  
Vol 141 (5) ◽  
pp. 1009-1020 ◽  
Author(s):  
M. INSULANDER ◽  
C. SILVERLÅS ◽  
M. LEBBAD ◽  
L. KARLSSON ◽  
J. G. MATTSSON ◽  
...  
Keyword(s):  
Disease Onset ◽  
Clinical Manifestations ◽  
Rrna Genes ◽  
Oocyst Wall ◽  
Pcr Rflp ◽  
Infection Source ◽  
Polymerase Chain ◽  
18S Rrna Genes ◽  
Common Infection

SUMMARYThis study describes the epidemiology and symptoms in 271 cryptosporidiosis patients in Stockholm County, Sweden. Species/genotypes were determined by polymerase chain reaction–restriction fragment-length polymorphism (PCR–RFLP) of theCryptosporidiumoocyst wall protein (COWP) and 18S rRNA genes. Species wereC. parvum(n=111),C. hominis(n=65),C. meleagridis(n=11),C. felis(n=2),Cryptosporidiumchipmunk genotype 1 (n=2), and a recently described species,C. viatorum(n=2). Analysis of the Gp60 gene revealed fiveC. hominisallele families (Ia, Ib, Id, Ie, If), and fourC. parvumallele families (IIa, IIc, IId, IIe). MostC. parvumcases (51%) were infected in Sweden, as opposed toC. hominiscases (26%). Clinical manifestations differed slightly by species. Diarrhoea lasted longer inC. parvumcases compared toC. hominisandC. meleagridiscases. At follow-up 25–36 months after disease onset, 15% of the patients still reported intermittent diarrhoea. In four outbreaks and 13 family clusters, a single subtype was identified, indicating a common infection source, which emphasizes the value of genotyping for epidemiological investigations.

scholarly journals 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ferdinando Nicoletti ◽  
Ingrid Philippens ◽  
Paolo Fagone ◽  
Clarence N. Ahlem ◽  
Christopher L. Reading ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Motor Impairment ◽  
Concurrent Administration ◽  
Polymerase Chain ◽  
Oxide Synthase ◽  
The Brain ◽  
Necrosis Factor

17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2 sec versus 90.9 sec,P<0.0001), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%,P=0.002; tumor necrosis factorα, 40%,P=0.038, and interleukin-1β, 33%,P=0.02) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle (P=0.003), and decreased the numbers of damaged neurons by 38% relative to vehicle (P=0.029). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation.

scholarly journals MOLECULAR IDENTIFICATION OF Bartonella henselae IN A SERONEGATIVE CAT SCRATCH DISEASE PATIENT WITH AIDS IN RIO DE JANEIRO, BRAZIL

2014 ◽  
Vol 56 (4) ◽  
pp. 363-365 ◽  
Author(s):  
Alexsandra R.m. Favacho ◽  
Isabelle Roger ◽  
Amanda K. Akemi ◽  
Adonai A. Pessoa JR. ◽  
Andrea G. Varon ◽  
...  
Keyword(s):  
Rio De Janeiro ◽  
Wide Spectrum ◽  
Bartonella Henselae ◽  
Disease Patient ◽  
Clinical Manifestations ◽  
Lymph Node Biopsy ◽  
Cat Scratch Disease ◽  
Chain Reaction ◽  
Node Biopsy ◽  
Polymerase Chain

Bartonella henselae is associated with a wide spectrum of clinical manifestations, including cat scratch disease, endocarditis and meningoencephalitis, in immunocompetent and immunocompromised patients. We report the first molecularly confirmed case of B. henselae infection in an AIDS patient in state of Rio de Janeiro, Brazil. Although DNA sequence of B. henselae has been detected by polymerase chain reaction in a lymph node biopsy, acute and convalescent sera were nonreactive.

scholarly journals Public Knowledge about and Detection of Canine Visceral Leishmaniasis in Urban Divinópolis, Brazil

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Carina Margonari ◽  
Júlia Alves Menezes ◽  
Marcele Neves Rocha ◽  
Kamila Nunes Maia ◽  
Michael Éder de Oliveira ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Disease Outbreak ◽  
Social Conditions ◽  
Public Knowledge ◽  
Canine Visceral Leishmaniasis ◽  
The Past ◽  
Pcr Rflp ◽  
Minas Gerais State

Background. Leishmaniases are diseases with a wide spectrum of clinical manifestations including cutaneous (CL) and visceral (VL) forms. Many factors may affect their occurrence and expansion including environmental, geographic, and social conditions. In the past two decades, Divinópolis, Minas Gerais State, Brazil, has exhibited the potential for a disease outbreak, with the appearance of CL, and VL cases (human and canine). Hence, this study was initiated to monitor public knowledge of the disease. Questionnaires were administered in four neighborhoods (Jardim Belvedere, Esplanada, Danilo Passos I and II) where most of the human and canine cases have been reported. The analyses demonstrated that public knowledge of the disease is sparse and fragmented. A strong perception of the dog as the main reservoir was observed. Five veterinary clinics were evaluated for the presence of canine VL using serological (RIFI and ELISA) and molecular (PCR-RFLP) techniques. This is the first study demonstrating the occurrence ofLeishmania infantumin Divinópolis, suggesting a possible urbanization of VL.

scholarly journals Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Alexsandro S Lago ◽  
Filipe R Lima ◽  
Augusto M Carvalho ◽  
Camilla Sampaio ◽  
Neuza Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Interferon Γ ◽  
Cure Rate ◽  
Cutaneous Lesions ◽  
Inflammatory Cytokine Production ◽  
Polymerase Chain ◽  
And Gender ◽  
Histopathologic Findings

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by 1 or multiple well-limited ulcerated lesions. Diabetes mellitus (DM) impairs neutrophil and monocyte function, and there is a report of vegetative lesions in a patient with both diseases in Morocco. Here we evaluate the influence of DM on clinical manifestations, immune response, and in the treatment of CL. Methods The participants were 36 DM patients with CL and 36 patients with CL without DM, matched by age and gender. The diagnosis of CL was performed by documentation of DNA of L. braziliensis by polymerase chain reaction in the lesion biopsy and histopathologic findings. All patients were treated with Glucantime (Sanofi-Aventis) 20 mg/kg of weight per day for 20 days. Results There was no difference in the majority of the clinical variables between the groups, and the cure rate in patients with CL and DM (67%) was similar to that observed in CL patients (56%; P ˃ .05). The most important finding was the documentation that 36% of the patients with DM and CL had atypical cutaneous lesions characterized by large superficial ulcers without defined borders. High levels of interferon-γ, tumor necrosis facor, and interleukin-1β were detected in the supernatants of mononuclear cells stimulated with Leishmania antigen in patients with DM and atypical CL. Moreover, while cure was observed in only 33% of the patients with DM and atypical CL lesions, it was observed in 85% of patients with typical lesions (P &lt; .05). Conclusions DM modifies the clinical presentation of CL, enhances pro-inflammatory cytokine production, and impairs response to antimony therapy.

scholarly journals Correlation of tumor necrosis factor-α -308G>A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study

2019 ◽  
Author(s):  
Maria Carmela Padula ◽  
Pietro Leccese ◽  
Nancy Lascaro ◽  
Rosa Paola Radice ◽  
Antonina Rita Limongi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Disease Severity ◽  
Tumor Necrosis ◽  
Wide Spectrum ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Genotype Distribution ◽  
Behçet Syndrome ◽  
Behcet Syndrome ◽  
Necrosis Factor

Abstract Background The tumor necrosis factor (TNF)α is a multifunctional proinflammatory cytokine, implicated in a variety of diseases, including Behçet syndrome (BS), a rare vasculitis with a wide spectrum of clinical manifestations. The aim of the present study was to investigate the association between a functional drug-response TNFα gene polymorphism (at the positions of -308; rs1800629) and both disease susceptibility and clinical manifestations in a cohort of Italian BS patients compared with healthy controls (HC).Methods We recruited 130 Italian patients with BS consecutively seen at Rheumatology Institute of Lucania (Italy) and 100 ethnically, age and gender matched HC. Demographic and clinical features were retrieved by medical records. Specific primer pairs were designed for TNFα coverage. Genomic DNA isolation, primer-specific PCR amplification and direct sequencing were performed for genotyping our group of patients and controls. In silico analysis was downstream performed using Mutation Surveyor software (SoftGenetics, USA) and NCBI-BlastN on line tool for the query-subject similarity analysis.Results The genotype distribution of BS patients and HC underlined a higher percentage of wild-type GG genotype in BS patients group vs HC (106/130 patients, 81.5% vs 91/100 HC, 91%; p<0.05), while the heterozygous genotype (GA) was identified in 24/130 patients (18.5%) vs 9/100 HC (9%) (p<0.05). GA genotype was significantly associated with the disease (OR=2.29, 95% CI 1.01-5.18). No significant association was recognized between the SNP and the BS clinical manifestations, as well as with disease severity (Krause's index).Conclusions We found statistically significant higher frequency of TNFα rs1800629 GA genotype in patients than in controls. No significant association was recognized between the polymorphism and the clinical parameters, as well as between the SNP and the disease severity. Our data need to be confirmed in larger cohort of patients and matched controls.

scholarly journals Population Structure ofLeishmania tropicaCausing Anthroponotic Cutaneous Leishmaniasis in Southern Iran by PCR-RFLP of Kinetoplastid DNA

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Amin Ghatee ◽  
Hossein Mirhendi ◽  
Masoud Marashifard ◽  
Zahra Kanannejad ◽  
Walter R. Taylor ◽  
...  
Keyword(s):  
Population Structure ◽  
Cutaneous Leishmaniasis ◽  
Fragment Length Polymorphism ◽  
Restriction Enzymes ◽  
Group Method ◽  
Kinetoplast Dna ◽  
Banding Patterns ◽  
Pair Group ◽  
Pcr Rflp ◽  
Polymerase Chain

Iran is one of the six countries with the most cutaneous leishmaniasis (CL) patients. Understanding better the genotypes of the parasite population in relation to geography and climate is critical to achieving better CL control. We aimed to characterise the population structure ofLeishmania tropica, the cause of anthroponotic cutaneous leishmaniasis (ACL), from important foci in southeast (Bam and Kerman) and southwest (Shiraz) Iran. A total of 39L. tropicaisolates from ACL patients from southeast (Bam 14, Kerman 12) and southwest (Shiraz 13) Iran were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) of the kinetoplast DNA (kDNA) using restriction enzymesMspI (HpaII) andClaI. 37 genotypes were identified among south IranL. tropicaisolates. The unweighted pair group method with arithmetic mean (UPGMA) tree obtained from the banding patterns ofClaI digested kDNA RFLP distinguished southeast from and southwestL. tropicaisolates with some subclustering but theMspI derived tree showed greater discrimination with greater subclustering and divergence of the two foci of southeast region but with some overlapping. Although a monophyletic structure has been defined for southeastL. tropica, isolates from two foci of southeast Iran were partly discriminated in the current study.

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