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1.
Echocardiography ; 41(3): e15777, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38526991

RESUMO

INTRODUCTION: Cardiac sarcoidosis (CS) is commonly diagnosed based on clinical criteria and abnormalities in noninvasive imaging reported in patients with biopsy-proven extracardiac sarcoidosis. Electrocardiogram and two-dimensional echocardiography have a low sensitivity for CS detection. Cardiovascular magnetic resonance imaging (CMR) and positron emission tomography (PET) have limitations in terms of cost and availability. OBJECTIVES: This study aimed to assess the usefulness of left ventricular longitudinal strain, measured using two-dimensional speckle tracking echocardiography (STE), for the prediction of late gadolinium enhancement (LGE) presence in CMR in patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: A total of 119 patients with biopsy-proven extracardiac sarcoidosis were divided, according to the clinical criteria proposed by the 2014 Heart Rhythm Society expert consensus statement (HRS 2014), into two groups: 43 individuals with "probable cardiac sarcoidosis", CS(+) and 76 individuals without cardiac sarcoidosis, CS (-). Data from echocardiography, CMR, 12-lead ECG and 24 h Holter monitoring were analyzed. RESULTS: Left ventricular global longitudinal strain (LV-GLS) was slightly reduced in the entire sarcoidosis group (-18.61± 2.96), no difference between the CS (+) and CS (-) subgroups was found (-18.0% ± 3.2% and -18.9% ± 2.8%, respectively; p = .223). No cut-off value for LV-GLS was identified that could predict the presence of LGE. Segmental longitudinal strain impairment partially correlated with the presence of LGE on CMR. CONCLUSIONS: In our cohort of sarcoidosis patients, segmental longitudinal strain proved more helpful in the diagnostic process than LV-GLS. The ultimate role of STE in the diagnosis of CS remains to be established.


Assuntos
Cardiomiopatias , Miocardite , Sarcoidose , Humanos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/patologia , Meios de Contraste , Gadolínio , Ecocardiografia/métodos , Sarcoidose/diagnóstico , Sarcoidose/diagnóstico por imagem , Biópsia , Imagem Cinética por Ressonância Magnética/métodos
2.
Int J Mol Sci ; 24(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36982159

RESUMO

Pathological similarities between sarcoidosis (SA) and tuberculosis (TB) suggest the role of mycobacterial antigens in the etiopathogenesis of SA. The Dubaniewicz group revealed that not whole mycobacteria, but Mtb-HSP70, Mtb-HSP 65, and Mtb-HSP16 were detected in the lymph nodes, sera, and precipitated immune complexes in patients with SA and TB. In SA, the Mtb-HSP16 concentration was higher than that of Mtb-HSP70 and that of Mtb-HSP65, whereas in TB, the Mtb-HSP16 level was increased vs. Mtb-HSP70. A high Mtb-HSP16 level, induced by low dose-dependent nitrate/nitrite (NOx), may develop a mycobacterial or propionibacterial genetic dormancy program in SA. In contrast to TB, increased peroxynitrite concentration in supernatants of peripheral blood mononuclear cell cultures treated with Mtb-HSP may explain the low level of NOx detected in SA. In contrast to TB, monocytes in SA were resistant to Mtb-HSP-induced apoptosis, and CD4+T cell apoptosis was increased. Mtb-HSP-induced apoptosis of CD8+T cells was reduced in all tested groups. In Mtb-HSP-stimulated T cells, lower CD8+γδ+IL-4+T cell frequency with increased TNF-α,IL-6,IL-10 and decreased INF-γ,IL-2,IL-4 production were present in SA, as opposed to an increased presence of CD4+γδ+TCR cells with increased TNF-α,IL-6 levels in TB, vs. controls. Mtb-HSP modulating the level of co-stimulatory molecules, regulatory cells, apoptosis, clonal deletion, epitope spread, polyclonal activation and molecular mimicry between human and microbial HSPs may also participate in the induction of autoimmunity, considered in SA. In conclusion, in different genetically predisposed hosts, the same antigens, e.g., Mtb-HSP, may induce the development of TB or SA, including an autoimmune response in sarcoidosis.


Assuntos
Mycobacterium tuberculosis , Sarcoidose , Tuberculose , Humanos , Proteínas de Choque Térmico/metabolismo , Mycobacterium tuberculosis/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Leucócitos Mononucleares/metabolismo , Interleucina-6/metabolismo , Interleucina-4/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo
3.
Int J Mol Sci ; 24(11)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37298666

RESUMO

Sarcoidosis (SA) is a granulomatous disorder, which mostly affects the lungs. Its clinical characteristics resemble tuberculosis (TB), but its treatment is different. The etiology of SA is unknown; however, mycobacterial antigens were proposed as environmental factors in its development. Due to previously revealed immunocomplexemia with mycobacterial antigens in the blood of our SA but not TB patients, and in the search for biomarkers for differential diagnosis of the two disorders, we studied the phagocytic activity of monocytes from both patients' groups with flow cytometry. With the use of this method, we also analyzed the occurrence of receptors for IgG (FcγR) and complement components (CR) at the surface of these monocytes, responsible for phagocytosis of immunocomplexes. We revealed a higher phagocytic activity of monocytes in both disorders, but an increased frequency of monocytes with FcγRIII (CD16) and decreased with CR1 (CD35) receptor in the blood of SA vs. TB patients. With regard to our other genetic study on FcγRIII variants in SA and TB, this may account for the decreased clearance of immunocomplexes and different immune responses in the two diseases. Thus, the presented analysis not only sheds light on the pathomechanisms of SA and TB but may also support their differential diagnosis.


Assuntos
Sarcoidose Pulmonar , Sarcoidose , Tuberculose , Humanos , Monócitos , Receptores de IgG , Receptores de Complemento , Fagocitose
4.
Immunol Cell Biol ; 100(8): 591-604, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35771184

RESUMO

Fcγ receptors (FcγRs) bind the Fc fragment of immunoglobulin G (IgG), mostly after IgG opsonizes a bacterial or viral antigen or danger/damage-associated molecule. Consequently, classic FcγRs initiate phagocytosis of the IgG-antigen immune complex and stimulate an immune reaction against the threat. Signals from activating FcγRs (FcγRI, FcγRIIa/c, FcγRIIIa/b) are balanced by inhibitory FcγRIIb and likely also by two FcR-like proteins (FCRL4 and FCRL5). The neonatal Fc receptor (FcRn) recirculates IgG and increases its half-life. The last FcγR that has been identified in humans, tripartite motif-containing protein 21 (TRIM21), acts toward pathogen destruction via the proteasomal or autophagic pathway. The expression of FcγRs occurs almost exclusively in immune cells. However, podocytes, key cells in the glomerular filtration barrier, also possess several features of an immune cell and express receptors for IgG. The presence of FcγRs in glomeruli was analyzed in the Human Protein Atlas project. FcγR occurrence in whole glomeruli or in particular resident kidney cells was also showed in a few original articles. In human podocytes only FcRn has been studied extensively, and the presence and role of other FcγRs remain obscure. Research on the genetic background of kidney diseases revealed a connection between FcγRs and several nephropathies. Investigations of FcγR expression in podocytes appear to be of great clinical importance. The present review discusses the latest literature on FcγRs in kidney cells (especially podocytes), with an emphasis on their involvement in kidney health and disease.


Assuntos
Fragmentos Fc das Imunoglobulinas , Receptores de IgG , Complexo Antígeno-Anticorpo/metabolismo , Proteínas de Transporte/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G , Rim/metabolismo , Receptores de IgG/metabolismo
5.
Am J Respir Crit Care Med ; 197(2): 225-234, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28846439

RESUMO

RATIONALE: The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers. OBJECTIVES: We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination. METHODS: We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing. MEASUREMENTS AND MAIN RESULTS: In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons. CONCLUSIONS: Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives.


Assuntos
DNA Bacteriano/análise , Metagenoma/genética , Microbiota/genética , Sarcoidose/genética , Sarcoidose/microbiologia , Biópsia por Agulha , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Teste de Kveim , Masculino , Valores de Referência , Sarcoidose/patologia , Sensibilidade e Especificidade , Inclusão do Tecido
6.
Eur Respir J ; 51(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29371378

RESUMO

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.


Assuntos
Fenótipo , Sarcoidose/diagnóstico , Sarcoidose/fisiopatologia , Abdome , Doença Aguda , Adulto , Idoso , Europa (Continente) , Olho/fisiopatologia , Oftalmopatias/fisiopatologia , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Artropatias/fisiopatologia , Pulmão/fisiopatologia , Pneumopatias/fisiopatologia , Linfonodos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pele/fisiopatologia , Dermatopatias/fisiopatologia , Atenção Terciária à Saúde , População Branca
7.
Pol Merkur Lekarski ; 44(261): 97-100, 2018 Mar 27.
Artigo em Polonês | MEDLINE | ID: mdl-29601556

RESUMO

In the light of modified the Matzinger's model of immune response, human heat shock proteins (hsp) as main "danger signals" tissue damage-associated molecular patterns (DAMPs) or/and microbial hsp as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through genetically changed PRR and persisting in genetically altered host phagocytes, generate increased release of both human and microbial hsp with their molecular and functional homology. High chronic spread of human and microbial hsp altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human hsp may be released at high levels during chronic low-grade exposure to misfolding amyloid precursor protein in stressed cells, phagocyted metal fumes, pigments with/ without aluminum in tattoos, and due to heat shock in firefighters. Therefore, human hsp as DAMPs and/or microbial hsp as PAMPs produced as a result of non-infectious and infectious factors may induce different models of sarcoidosis, depending on the genetic background of the host.


Assuntos
Autoimunidade , Doenças Transmissíveis/complicações , Sarcoidose/etiologia , Sarcoidose/imunologia , Humanos , Sarcoidose/microbiologia , Transdução de Sinais
8.
Pol Merkur Lekarski ; 44(261): 91-96, 2018 Mar 27.
Artigo em Polonês | MEDLINE | ID: mdl-29601555

RESUMO

In the light of modified the Matzinger's model of immune response, human heat shock proteins (hsp) as main 'danger signals' (tissue damage-associated molecular patterns-DAMPs) or/and microbial hsp as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host.


Assuntos
Predisposição Genética para Doença , Polimorfismo Genético , Sarcoidose/etiologia , Sarcoidose/genética , Doenças Transmissíveis/complicações , Humanos , Sarcoidose/metabolismo , Sarcoidose/microbiologia , Transdução de Sinais
9.
Pol Merkur Lekarski ; 44(261): 101-109, 2018 Mar 27.
Artigo em Polonês | MEDLINE | ID: mdl-29601557

RESUMO

Sarcoidosis (SA) is a granulomatous multisystem disease of unknown ethiology. Pulmonary, lymphadenopathy, liver, spleen, skin, and bone sarcoidosis are more frequent but also SA of the heart, central nervous system, eye, and hypercalcemia with following kidney failure also occur. Sarcoidosis may co-exist with extrapulmonary forms, which may overtake or precede each other. SA may occur as acute or chronic with the possibility of complete remission in the early stages of disease. Due to frequent occurrence of asymptomatic SA in threatening vital organs a diagnostic algorithm of practice in pulmonary and extrapulmonary sarcoidosis has been proposed by the author of the article. Diagnosis of SA is based on a correlation of clinical, radiological and histopathological pictures with the presence of non-caseating granuloma in material from the biopsy from at least one organ and having excluded tuberculosis. In all forms of SA, USG abdomen, ECG, ECHO heart, blood tests (blood count, calcium, creatinine, transaminases), level of calcium in a 24-hour urine samples, ophtalmoscopic examinations and lung function tests in pulmonary sarcoidosis should be undertaken to avoid overlooking any form of SA, especially in threatened vital organs. For this purpose, the multidisciplinary team providing an adequate care to the patient with SA has been created by the author of the article has been created by the author of the article in the University Clinical Center in Gdansk providing comprehensive care to patients with sarcoidosis.


Assuntos
Sarcoidose/diagnóstico , Algoritmos , Biópsia , Diagnóstico Diferencial , Humanos , Sarcoidose/etiologia , Sarcoidose/metabolismo , Sarcoidose/patologia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/etiologia , Sarcoidose Pulmonar/metabolismo , Sarcoidose Pulmonar/patologia
10.
Pol Merkur Lekarski ; 44(261): 130-134, 2018 Mar 27.
Artigo em Polonês | MEDLINE | ID: mdl-29601562

RESUMO

Sarcoidosis (SA) is a granulomatous, multisystem disease of unknown etiology. Most often the disease affects lungs and mediastinal lymph nodes, but it may occur in other organs. Neurosarcoidosis (NS) more commonly occurs with other sarcoidosis forms, in 1% of cases it involves only nervous system. Symptomatic NS occurs but on autopsy study up to 25% of cases are confirmed. NS can affect central nervous system: the brain, spinal cord and peripheral nerves, and muscles. The diagnosis of neurosarcoidosis facilitates diagnostic criteria: histopathological, imaging and cerebrospinal fluid examination, and clinical symptoms. At present, there are no set standards for treatment of patients suffering from NS. Early therapy of symptomatic patients is recommended. Corticosteroids still are the first line of treatment for NS patients. In cases of steroids resistance, lack of their effectiveness or existence of contraindication to their use, immunosuppressant treatment is recommended. The latest NS algorithm with immunosuppressive treatment is discussed.


Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Sarcoidose/diagnóstico , Corticosteroides/uso terapêutico , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/patologia , Humanos , Imunossupressores/uso terapêutico , Guias de Prática Clínica como Assunto , Sarcoidose/líquido cefalorraquidiano , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia
11.
Pol Merkur Lekarski ; 44(261): 142-146, 2018 Mar 27.
Artigo em Polonês | MEDLINE | ID: mdl-29601565

RESUMO

Skin manifestation occurs in approximately 25% of patients with sarcoidosis and is often the first symptom of the disease. The availability of skin biopsy material is helpful in establishing the early diagnosis. Cutaneous sarcoidosis is characterized by clinical polymorphism and therefore its diagnosis may cause dilemma. The systemic sarcoidosis should be excluded in every patient with cutaneous sarcoidosis, because systemic involvement has a significant impact on course, treatment and prognosis of the disease.


Assuntos
Sarcoidose/diagnóstico , Dermatopatias/diagnóstico , Biópsia , Humanos , Guias de Prática Clínica como Assunto , Sarcoidose/patologia , Pele/patologia , Dermatopatias/patologia
12.
Cells ; 12(9)2023 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-37174624

RESUMO

The clinical outcome of sarcoidosis (SA) is very similar to tuberculosis (TB); however, they are treated differently and should not be confused. In search for their biomarkers, we have previously revealed changes in the phagocytic activity of monocytes in sarcoidosis and tuberculosis. On these monocytes we found a higher expression of receptors for the Fc fragment of immunoglobulin G (FcγR) in SA and TB patients vs. healthy controls. FcγRs are responsible for the binding of immune complexes (ICs) to initiate an (auto)immune response and for ICs clearance. Surprisingly, our SA patients had a high blood level of ICs, despite the abundant presence of FcγRs. It pointed to FcγR disfunction, presumably caused by the polymorphism of their (FCGR) genes. Therefore, we present here an analysis of the occurrence of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B variants in Caucasian SA and TB patients, and healthy individuals with the use of polymerase chain reaction (PCR) and real-time PCR. The presented data point to a possibility of supporting the differential diagnosis of SA and TB by analyzing FCGR2C, FCGR3A and FCGR3B polymorphism, while for severe stages of SA also by studying FCGR2A variants. Additionally, the genotyping of FCGR2A and FCGR3B might serve as a marker of SA progression.


Assuntos
Receptores de IgG , Sarcoidose Pulmonar , Tuberculose , Humanos , Polimorfismo de Nucleotídeo Único , Receptores de IgG/genética , Sarcoidose Pulmonar/genética , Tuberculose/genética
13.
Gene ; 878: 147577, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37336276

RESUMO

Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Löfgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 × 10-3), non-LS (OR = 0.66, p = 2.71 × 10-4) and CXR stages 2-4 (OR = 0.62, p = 7.48 × 10-5) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 × 10-8), TNFA rs1800629 (OR = 1.56, p = 6.65 × 10-4), ATF6B rs3130288 (OR = 2.75, p = 1.06 × 10-9) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 × 10-4) with sarcoidosis compared to controls. For sub-phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 × 10-12), TNFA rs1800629 (OR = 2.66, p = 5.94 × 10-7), ATF6B rs3130288 (OR = 5.24, p = 5.21 × 10-13), LRRC16A rs9295661 (OR = 2.97, p = 4.29 × 10-4), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 × 10-6) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 × 10-13) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 × 10-4) and ATF6B rs3130288 (OR = 2.15, p = 3.36 × 10-5) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 × 10-11), TNFA rs1800629 (OR = 1.84, p = 1.32 × 10-4), ATF6B rs3129927 (OR = 3.63, p = 1.82 × 10-11), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 × 10-5) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 × 10-10) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 × 10-4), ATF6B rs3129927 (OR = 2.23, p = 3.52 × 10-5) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 × 10-3) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.


Assuntos
Estudo de Associação Genômica Ampla , Sarcoidose , Humanos , Cadeias alfa de HLA-DR/genética , Sarcoidose/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Gerenciamento Clínico , Predisposição Genética para Doença
14.
Front Med (Lausanne) ; 10: 1218106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621457

RESUMO

Introduction: Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures. Methods: After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations. Results: In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement. Discussion: The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.

15.
Pneumonol Alergol Pol ; 83(4): 339-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26378287

Assuntos
Sarcoidose , Humanos , Polônia
16.
Sarcoidosis Vasc Diffuse Lung Dis ; 35(2): 160-164, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32476897

RESUMO

Background: Fatigue is one of the most common and disabling symptoms of sarcoidosis. The cause of fatigue remains unclear and is usually multifactorial. The majority of previous studies evaluated clinical parameters with only few of them including assessment of psychological factors as contributing to the severity of the symptoms. Objective: The aim of this study was to evaluate the relationship of emotional distress, physical concerns, and dyspnea in explaining fatigue in patients with sarcoidosis. Methods: Fifty-seven patients with sarcoidosis were enrolled to the study and filled out measures of fatigue (FAS), dyspnea (MRC), anxiety sensitivity (ASI-3), and anxiety and depression (HADS). Results: Linear regression revealed that distress and physical concerns subscale of ASI are significant predictors of fatigue explaining jointly 53.5% of fatigue variance. Conclusions: The results of the study emphasize the importance of including emotional distress and physical concerns into the diagnostic procedures and management of fatigue in sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 160-164).

17.
Respir Med ; 101(10): 2213-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17662590

RESUMO

BACKGROUND: Sarcoidosis (SA) is a multisystem granulomatous disorder of unknown etiology. It seems likely that in genetically different predisposed hosts, the same antigen(s) may cause the development of sarcoid Th1 response. The interaction of the T-cell receptor with the human leukocyte antigen-DQA1*03011 peptide-complex can affect T lymphocytes activation in a dose-response manner. OBJECTIVES/METHODS: To test occurrence of DQA1*03011 allele in SA, we compared the distribution of DQA1 alleles in 32 SA patients, 37 TB patients and in 58 healthy volunteers, using a PCR-SSP "high-resolution" method. RESULTS: Our results revealed that after Bonferroni correction DQA1*03011 were less common in SA patients than in the controls (OR 0.16, 95%CI 0.03-0.75). In TB, DQA1*0303 were significantly more frequent and DQA1*0505 less present as compared to the controls (OR 11.03, 95% CI 1.20-95.80, OR 0.29, 95% CI 0.01-0.88). Comparing DQA1 alleles in both patient groups, DQA1*0501, DQA1*0505 alleles were more common and DQA1*03011, DQA1*0302, DQA1*0303 were less common after Bonferroni correction in SA than in TB. CONCLUSION: We revealed that DQA1*03011 allele was less common in SA than in the controls and TB. It seems possible that a low frequency of DQA1*03011 occurrence may be also involved in the etiopathogenesis of SA.


Assuntos
Frequência do Gene/imunologia , Antígenos HLA/genética , Polimorfismo Genético/imunologia , Sarcoidose Pulmonar/genética , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Sarcoidose Pulmonar/imunologia
18.
Pneumonol Alergol Pol ; 75(1): 13-21, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-17541908

RESUMO

INTRODUCTION: Sarcoidosis is a multisystem disorder of unknown etiolgy. Pathologic similarities between SA and tuberculosis (TB) suggest M. tuberculosis antigen(s) as causative agents. It seems likely that in the genetically different predisposed hosts, the same antigen(s) may cause the development of sarcoid or tuberculous immune response. AIM: The aim of this study was to compare the frequency of occurrence of HLA class II alleles in SA, TB and in the healthy individuals. MATERIAL AND METHODS: To test a difference in haplotypes associated with both diseases, we compared the distribution of DQA1 and DQB1 alleles in 45 SA patients, 62 TB patients and in 143 healthy volunteers, using a PCR-SSP "low (DRB1, DQB1) and high (DQA1) resolution" method. RESULTS: Our results revealed that DRB1*03, DRB1*11, DQB1*02 i DQA1*0501 in Stage I of SA with Löfgrens syndrom (Ls) and DRB1*15, DQA1*0102, DQA1*0103 in Stage II of SA were more common, whereas DRB1*16, DRB1*04, DRB1*08, DQB1*02, DQB1*03, DQB1*05, DQA1*0102, DQA1*0301 in Ls and DQB1*02, DQB1*03, DQB1*05, DQA1*0102, DQA1*0301 in Stage II were less common than in the controls but after Bonferroni correction occurrence of DRB1*04, DQB1*02, DQB1*03, DQB1*05 and DQA1*0102, DQA1*0301, DQA1*0501 was significantly differ. In TB group, DRB1*16, DRB1*14, DQB1*05 i DQA1*0303 were more frequent and DRB1*11, DQB1*02, DQA1*0201, DQA1*0505 less frequently present as compared to the controls, but after correction DRB1*16, DQB1*02, DQB1*05, DQA1*0303, DQA1*0505 were significantly different. In SA, DRB1*11, DQB1*02 i DQA1*0201, DQA1*0501, DQA1*0505 in Ls and DRB1*15, DRB1*11, DQA1*0102 in Stage II were more common and DRB1*16, DRB1*04, DRB1*14, DQB1*03, DQB1*05, DQB1*06, DQA1*0301, DQA1*0302, DQA1*0303 in Ls and Stage II were less frequent than in the TB group. DQB1*02, DQA1*0501 (Ls) and DRB1*15 (Stage II) were more frequently present in SA than in TB, even after Bonferroni correction. CONCLUSIONS: In summary, we identified associations of HLA class II alleles in SA and TB with expression pattern specific and different for each group. In most cases, in SA patients frequency of HLA class II alleles occurrence is opposite to the frequency in TB patients.


Assuntos
Alelos , Frequência do Gene , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Mycobacterium tuberculosis/genética , Sarcoidose/genética , Tuberculose/genética , Adolescente , Adulto , Idoso , Animais , Feminino , Predisposição Genética para Doença/epidemiologia , Genética Populacional , Antígenos HLA-DQ/classificação , Antígenos HLA-DR/classificação , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Polimorfismo Genético , Valores de Referência , Sarcoidose/epidemiologia , Tuberculose/epidemiologia
19.
Gen Hosp Psychiatry ; 47: 43-47, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28807137

RESUMO

OBJECTIVE: The purpose of the study was to evaluate the relationship of an objective functional lung parameter (FVC) and a subjective psychological factor (physical symptom concerns) with dyspnea in sarcoidosis. Dyspnea constitutes one of the most common and burdensome symptoms in sarcoidosis, yet little is known about its mechanisms and, in particular, psychological. METHOD: A total of 107 hospitalized sarcoidosis patients (Female=50, Mage=45.3years) volunteered to take part in the correlational research study. Participants underwent spirometry and completed the MRC Dyspnea Scale and the Anxiety Sensitivity Index-3 (ASI) questionnaire. Linear hierarchical regression analysis was used to determine the relationship between the studied predictors and dyspnea severity. RESULTS: The best fitting model predicted 18% of variance in dyspnea severity. Physical symptom concerns subscale of ASI (ß=0.24) and FVC (ß=-0.23) were significantly related to dyspnea MRC severity, but only physical concerns remained significantly related to dyspnea when both predictors were in the model. CONCLUSIONS: The current results suggest that both psychological and physiological factors should be taken into account when explaining subjective dyspnea severity in sarcoidosis. More specifically, these findings call for including cognitive vulnerability factors related to anxiety (physical symptom concerns) into the diagnostic procedures and management of dyspnea in sarcoidosis.


Assuntos
Ansiedade/psicologia , Dispneia/fisiopatologia , Sarcoidose Pulmonar/psicologia , Capacidade Vital/fisiologia , Adulto , Dispneia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/complicações , Índice de Gravidade de Doença , Espirometria
20.
PLoS One ; 12(5): e0177194, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28472129

RESUMO

We have previously revealed that, in contrast to polymorphism of FCGR2B and FCGR3B, polymorphism of FCGR2A, FCGR2C and FCGR3A genes, encoding receptors for Fc fragment of immunoglobulin G (Fcγ receptors), play a role in increased level of circulating immune complexes with occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis. However, this immunocomplexemia might also be caused by decreased clearance by immune cells due to a changed copy number of FCGR genes. Thus, the next step of our study was to evaluate copy number variation of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B in this disease. The analysis was carried out by real-time quantitative PCR on 104 patients and 110 healthy volunteers. Despite previously detected variation in allele/genotype frequencies of FCGR in sarcoidosis and its particular stages, there was no copy number variation of the tested genes between sarcoidosis or its stages and healthy control, as well as between stages themselves. A relevant increase in copy number of FCGR2C and FCGR3B in Stage IV of sarcoidosis vs. other stages and controls was detected, but this observation was based on a limited number of Stage IV patients. Hence, polymorphism of FCGR genes seems to be more important than their copy number variation in etiopathogenesis of sarcoidosis in patients from the Polish population.


Assuntos
Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Receptores de IgG/genética , Sarcoidose/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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