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1.
Contact Dermatitis ; 77(3): 159-162, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28421670

RESUMO

BACKGROUND: In 2016, dermatologists in Finland suspected contact allergy in several patients using moisturizers under the trade name Apobase®. Following a formulation change, Phenostat™, which is a mixture of phenoxyethanol, caprylhydroxamic acid, and methylpropanediol, was used as a preservative in Apobase® moisturizers in Finland. OBJECTIVES: To confirm the suspected contact allergy to Apobase® cream, oily cream, and/or lotion, and to identify the specific contact allergen and define its optimal patch test concentration. METHODS: Thirty-nine patients with suspected contact allergy to Apobase® creams or lotion were patch tested in four Finnish dermatological clinics. The patch tests included old and new Apobase® formulas and their preservative agents: phenoxyethanol, methylpropanediol, and dilution series of Phenostat™ and caprylhydroxamic acid or its potassium salt. RESULTS: The patch tests showed positive reactions to the new Apobase® formulas, Phenostat™, and caprylhydroxamic acid or its potassium salt, but not to the old Apobase® formulas, methylpropanediol, or phenoxyethanol. CONCLUSIONS: We found a new contact allergen, caprylhydroxyamic acid, which caused an epidemic of allergic contact dermatitis in patients using moisturizers containing this preservative. Whether the sensitizing capacity of caprylhydroxamic acid depends on the other chemicals used in Apobase® moisturizers needs further investigation.


Assuntos
Alérgenos/efeitos adversos , Caprilatos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Adulto , Feminino , Finlândia , Dermatoses da Mão/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/efeitos adversos , Conservantes Farmacêuticos
2.
Exp Dermatol ; 24(7): 510-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25827949

RESUMO

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10(-8) ): rs2187668 (PGWAS  = 1.4 × 10(-12) ), rs9267531 (PGWAS  = 4.7 × 10(-10) ), rs4410767 (PGWAS  = 1.0 × 10(-9) ) and rs3094084 (PGWAS  = 1.1 × 10(-9) ). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21).


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Cutâneo/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Transporte/genética , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 6/genética , Finlândia , Estudo de Associação Genômica Ampla , Alemanha , Cadeias alfa de HLA-DQ/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Lúpus Eritematoso Cutâneo/imunologia , Complexo Principal de Histocompatibilidade , Ribonuclease P/genética , Ubiquitina-Proteína Ligases
3.
Nephron Clin Pract ; 124(1-2): 17-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24029861

RESUMO

BACKGROUND/AIMS: Chronic kidney disease (CKD) patients on dialysis are prone to vitamin D insufficiency despite oral vitamin D supplementation. Here, we studied whether narrow-band ultraviolet B (NB-UVB) exposures improve vitamin D balance. METHODS: 14 haemodialysis patients and 15 healthy subjects receiving oral cholecalciferol 20 µg daily got nine NB-UVB exposures on the entire body. Serum 25-hydroxyvitamin D (25(OH)D) was measured by radioimmunoassay. Cutaneous mRNA expression levels of CYP27A1 and CYP27B1, two enzymes required for hydroxylation of vitamin D into its active metabolite, were also measured. RESULTS: The baseline serum 25(OH)D concentration was 57.6 ± 18.2 nmol/l in the CKD patients and 74.3 ± 14.8 nmol/l in the healthy subjects. The NB-UVB course increased serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0 nmol/l (CI 13.7-20.2), respectively. At baseline the CKD patients showed significantly increased CYP27B1 levels compared to the healthy subjects. CONCLUSIONS: A short NB-UVB course is an efficient way to improve vitamin D balance in CKD patients on dialysis who are receiving oral vitamin D supplementation. The increased cutaneous CYP27B1 levels in the CKD patients suggest that the loss of renal activity of this enzyme is at least partially compensated for by the skin.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Colestanotriol 26-Mono-Oxigenase/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Pele/metabolismo , Deficiência de Vitamina D/terapia , Vitamina D/administração & dosagem , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Administração Oral , Adolescente , Idoso , Colestanotriol 26-Mono-Oxigenase/genética , Terapia Combinada/métodos , Suplementos Nutricionais , Feminino , Humanos , Masculino , RNA Mensageiro/metabolismo , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Pele/efeitos da radiação , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Resultado do Tratamento , Terapia Ultravioleta/métodos , Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/metabolismo , Adulto Jovem
4.
Rheumatology (Oxford) ; 51(1): 87-92, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22039224

RESUMO

OBJECTIVE: A large number of genes, including several not previously implicated in SLE susceptibility, have recently been identified or confirmed by genome-wide association studies (GWAS). In this study, we sought to replicate some of these results in Finnish SLE patients (n = 275) and control individuals (n = 356). METHODS: We genotyped 32 single nucleotide polymorphisms (SNPs) in 12 of the best-supported GWAS-identified SLE genes and loci. We further investigated gene-gene interactions between the loci included in the study. RESULTS: The strongest evidence of association was found at the IRF5-TNPO3 locus, with the most significant P-value being 2.0 × 10(-7) and an odds ratio of 1.95 (95% CI 1.51, 2.50). Association between SLE and TNFAIP3, FAM167A-BLK, BANK1 and KIAA1542 was also confirmed, although at a lower significance level and contribution to individual risk. No significant association was found with 1q25.1, PXK, ATG5, ICA1, XKR6, LYN and SCUBE1. Furthermore, no significant gene-gene interactions were detected. CONCLUSION: Replication of previous GWAS findings across diverse populations is of importance to validate these associations and to get a better understanding of potential genetic heterogeneity between populations in SLE susceptibility. Our results attest the importance of B-cell receptor pathway and IFN signalling in SLE pathogenesis.


Assuntos
Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Receptores de Antígenos de Linfócitos B/fisiologia , Estudos de Casos e Controles , Epistasia Genética/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/imunologia , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética
5.
Nephrol Dial Transplant ; 27(6): 2435-40, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22180542

RESUMO

BACKGROUND: Chronic kidney disease (CKD) patients are especially prone to vitamin D insufficiency. Narrow-band ultraviolet B (NB-UVB) treatment increases serum 25-hydroxyvitamin D [25(OH)D] in dermatological patients, and we studied whether it also improves vitamin D balance in CKD patients on haemodialysis. METHODS: Fifteen dialysis patients (mean age 48.3 years) and 12 healthy subjects (mean age 43.6 years) received nine NB-UVB exposures on the upper body. Serum 25(OH)D and 1,25(OH)(2)D were measured before and after the exposures. From skin biopsy specimen messenger RNA (mRNA) expression levels of CYP24A1 and CYP27B1, two enzymes needed for hydroxylation of vitamin D into its active metabolites, and of antimicrobial peptide cathelicidin, were examined. RESULTS: Before NB-UVB, mean serum 25(OH)D was 32.5 ± 10.2 nmol/L in the dialysis patients and 60.2 ± 18.0 nmol/L in the healthy subjects (P < 0.001). After eight NB-UVB exposures, serum 25(OH)D increased by 13.8 nmol/L (43%; P < 0.001) and serum 1,25(OH)(2)D by 3.3 pmol/L (27%; P = 0.002) in the dialysis patients. After NB-UVB exposures, CYP27B1 mRNA was increased (P = 0.04), whereas cathelicidin mRNA was decreased (P < 0.0001) compared to non-treated healthy subjects. One and 2 months after NB-UVB exposure, serum 25(OH)D was still 10% higher than initially in the dialysis patients. CONCLUSIONS: The present study shows that a short course of NB-UVB exposure increases significantly serum 25(OH)D and 1,25(OH)(2)D in dialysis patients. The effect is, however, short lasting suggesting that the patients need cyclic NB-UVB exposure to maintain their improved vitamin D concentration.


Assuntos
Diálise Renal/efeitos adversos , Pele/efeitos da radiação , Raios Ultravioleta , Terapia Ultravioleta , Deficiência de Vitamina D/prevenção & controle , Vitamina D/análogos & derivados , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adolescente , Adulto , Idoso , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Vitamina D3 24-Hidroxilase , Adulto Jovem , Catelicidinas
6.
Contact Dermatitis ; 64(1): 49-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21166817

RESUMO

BACKGROUND: Antimicrobials constitute the second most common cause of contact allergy to cosmetics. Methylisothiazolinone (MI), previously always used together with methylchloroisothiazolinone (MCI), has recently been approved in the EU for use on its own in cosmetics and also various industrial products. MCI has been classified as an extreme-strong and MI as a strong-moderate sensitizer. OBJECTIVES: To study the frequency of positive patch test reactions to MI, and its relevance and relation to MCI/MI sensitivity, in Finland. METHODS: Over a period of 3 years (2006-2008), MI 0.1% (1000 ppm) and 0.03% (300 ppm) were patch tested in 10,821 patients at eight Finnish dermatological clinics. During 2008, patients with positive reactions to MI were asked to take part in a repeated open application test (ROAT). RESULTS: Of the patients tested, 1.4% and 0.6% showed positive patch test reactions to 0.1% and 0.03% MI, respectively. Sixty-six per cent of those who were MI-positive were also positive to 100 ppm MCI/MI. Thirty-three agreed to undergo the use test, and 10 of these gave positive results (30%). CONCLUSIONS: Our data show that MI used alone also potentially induces contact allergy. Careful monitoring is needed to determine whether or not this antimicrobial is safe to use in cosmetics.


Assuntos
Cosméticos/química , Dermatite Alérgica de Contato/etiologia , Conservantes Farmacêuticos/efeitos adversos , Tiazóis/efeitos adversos , Finlândia , Humanos , Testes do Emplastro
7.
Exp Dermatol ; 19(2): 123-31, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19758313

RESUMO

Lupus erythematosus (LE) is a heterogeneous disease ranging from skin-restricted manifestations to a progressive multisystem disease. The specific skin lesions include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both genetic and environmental factors are involved in the development of LE. However, reports on the genetic background of cutaneous lupus erythematosus (CLE) forms, namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are sparse. We investigated whether the known systemic LE (SLE) susceptibility genes also predispose to CLE. Altogether, 219 Finnish patients with DLE or SCLE and 356 healthy controls were recruited. Single nucleotide polymorphisms tagging reported risk genes were genotyped. Tyrosine kinase 2 (TYK2) rs2304256 was associated with increased risk of DLE (P = 0.012, OR = 1.47, 95% CI = 1.01-1.98). Expression of TYK2 was demonstrated by immunohistochemistry in macrophage-like cells and neutrophils and interferon regulatory factor 5 (IRF5) in macrophage- and fibroblast-like cells of DLE, SCLE and SLE skin. IRF5 rs10954213 showed association with DLE (P = 0.017, OR = 1.40, 95% CI = 1.06-1.86) and SCLE (P = 0.022, OR = 1.87, 95% CI = 1.09-3.21). A haplotype of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) showed association with DLE (P = 0.0065, OR = 2.51, 95% CI = 1.25-5.04). Our results show that the TYK2, IRF5 and CTLA4 genes previously associated with SLE also confer risk for DLE and SCLE, suggesting that different LE subphenotypes may share pathogenetic pathways.


Assuntos
Antígenos CD/genética , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Discoide/genética , TYK2 Quinase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CTLA-4 , Estudos de Casos e Controles , Feminino , Finlândia , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regulação para Cima , Adulto Jovem
8.
Contact Dermatitis ; 63(1): 37-41, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20597932

RESUMO

BACKGROUND: Thiourea derivatives in rubber products may induce contact sensitization and allergic contact dermatitis. Sensitization is most often from neoprene rubber, but the multitude of possible sensitizing products has remained poorly characterized. OBJECTIVE: The aim of this study was to collect information on the occurrence of thiourea-related contact allergy and to show novel sources of sensitization. PATIENTS AND METHODS: A mixture of dibutyl-, diethyl-, and diphenylthiourea was included in patch test baseline series in five Finnish dermatology clinics during 2002-2007. In addition, an extended series of rubber chemicals was tested in patients with suspected rubber allergy. Sources of sensitization to thioureas were analysed in sensitized patients. RESULTS: Thiourea mix yielded positive patch test reactions in 59 of 15,100 patients (0.39%); 33/59 patients were also tested with individual rubber chemicals. Diethylthiourea was positive in 24/33, diphenylthiourea in 5, and dibutylthiourea in 1 patient. The most common sources of sensitization included various neoprene-containing orthopaedic braces, sports equipment, and foot wear. CONCLUSIONS: The sources of sensitization to thiourea chemicals were detected in most cases. These sources comprise a heterogenous group of products extending from orthopaedic materials to sports equipment.


Assuntos
Dermatite Alérgica de Contato/etiologia , Hipersensibilidade ao Látex/etiologia , Borracha/química , Tioureia/análogos & derivados , Adolescente , Adulto , Idoso , Braquetes , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Feminino , Finlândia/epidemiologia , Humanos , Hipersensibilidade ao Látex/diagnóstico , Hipersensibilidade ao Látex/epidemiologia , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Borracha/efeitos adversos , Sapatos , Equipamentos Esportivos , Tioureia/efeitos adversos , Adulto Jovem
9.
Contact Dermatitis ; 62(2): 88-96, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20136891

RESUMO

BACKGROUND: Chairs and sofas imported from China to Europe were shown to contain dimethyl fumarate (DMF), a sensitizing, volatile chemical. Many of the sensitized patients also had positive patch test reactions to acrylates. OBJECTIVES: To analyse the occurrence and strength of DMF sensitization and the appearance of concomitant reactions. METHODS: Patch testing with DMF in concentrations of 0.1-0.00001% was carried out in 37 patients. Diethyl fumarate (DEF), diethyl maleate (DEM), dimethyl maleate (DMM), ethyl acrylate (EA), methyl acrylate (MA), and methyl methacrylate (MMA) were also tested with a dilution series at equimolar concentrations. RESULTS: The lowest concentration of DMF eliciting a reaction varied between 0.0001% and 0.1% and all but four patients reacted concurrently to DEF. DEM elicited positive patch test reactions in 21/37 patients and DMM reactions were seen in all 9 patients tested. EA elicited positive reactions in 13/37 patients and a positive MA reaction was seen in 7/37 patients, 2 of whom also reacted to MMA. CONCLUSIONS: The strength of the sensitization to DMF showed variation and concurrent reactions were common. Concurrent reactions to (meth)acrylates were seen in patients, who reacted to lower (0.001% or less) DMF concentration probably elicited by cross-reactivity.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Fumaratos/toxicidade , Testes do Emplastro , Acrilatos/química , Acrilatos/toxicidade , Adulto , China , Dermatite Alérgica de Contato/epidemiologia , Fumarato de Dimetilo , Feminino , Finlândia/epidemiologia , Fumaratos/química , Humanos , Decoração de Interiores e Mobiliário , Masculino , Maleatos/química , Maleatos/toxicidade , Metilmetacrilato/química , Metilmetacrilato/toxicidade , Pessoa de Meia-Idade , Reino Unido/epidemiologia
10.
Duodecim ; 126(12): 1393-9, 2010.
Artigo em Fi | MEDLINE | ID: mdl-20617744

RESUMO

Lupin, a legume with good nutritional value, is used in food production today, most often in bakery products. In Finland, lupin is a labelled ingredient in very few products. Clinically relevant lupin allergy, even anaphylaxis, often occurs in patients without atopic background or other food allergies, whereas lupin sensitization without clinical relevancy most commonly seems to represent cross reactivity to other legumes. Lupin allergy should be suspected and studied in patients with adverse reactions to food, and patients with allergy to other legumes should be advised about possible lupin allergy, as well.


Assuntos
Hipersensibilidade Alimentar/imunologia , Lupinus/imunologia , Humanos
14.
16.
PLoS One ; 5(12): e14212, 2010 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-21151989

RESUMO

BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. PRINCIPAL FINDINGS: To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value  = 4.73×10(-11), OR  = 3.20, 95% CI  = 2.23-4.57). Significant association was also detected to SLE patients (P-value  = 8.29×10(-6), OR  = 2.14, 95% CI  = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value  = 3.59×10(-8), OR  = 3.76, 95% CI  = 2.29-6.18). SIGNIFICANCE: We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.


Assuntos
Antígeno CD11b/genética , Lúpus Eritematoso Discoide/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Finlândia , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco , Suécia
17.
Ann Allergy Asthma Immunol ; 103(3): 233-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19788021

RESUMO

BACKGROUND: Lupin, a legume with good nutritional value, is used in food production today, most often in bakery products. Lupin sensitization is often seen among patients with reactions to legumes, but the number of reports describing lupin anaphylaxis is also increasing. OBJECTIVE: To investigate the occurrence of lupin sensitization, cross-reactivity, and lupin allergy among patients with suspected food allergy in Finland, where lupin is a labeled ingredient in few products. METHODS: The occurrence of positive skin prick test (SPT) reactions to lupin seed flour was studied among 1522 patients with suspected food allergy from November 1, 2005, through December 31, 2007. Clinical histories and diagnostic SPT results were analyzed among patients with positive SPT results to lupin. For 1 patient, ImmunoSpot and lupin radioallergosorbent test inhibition methods were used. RESULTS: Lupin sensitization was shown in 25 of 1522 patients (1.6%), and probable lupin allergy was diagnosed in 7 of 25 patients, in whom the clinical symptoms varied from anaphylaxis and respiratory symptoms to contact urticaria and itchy mouth. Cross-reactions or concurrent reactions to other legumes were seen in 18 of 25 patients. CONCLUSIONS: Clinically relevant lupin allergy often occurs in patients without atopic background or other food allergies, although lupin sensitization most commonly seems to represent cross-reactivity to other legumes. The occurrence of lupin allergy in a country where lupin has not been traditionally used is surprisingly common, suggesting that short-term use of modest amounts of lupin can cause serious allergic reactions.


Assuntos
Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Respiratória/diagnóstico , Adolescente , Adulto , Angioedema , Antígenos de Plantas/imunologia , Criança , Reações Cruzadas , Dispneia , Feminino , Finlândia , Farinha/efeitos adversos , Farinha/análise , Contaminação de Alimentos/análise , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/fisiopatologia , Humanos , Imunização , Imunoglobulina E/sangue , Incidência , Lupinus/efeitos adversos , Lupinus/química , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/fisiopatologia , Testes Cutâneos
18.
J Rheumatol ; 36(8): 1631-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19567624

RESUMO

OBJECTIVE: Several candidate genes have been implicated in susceptibility for systemic lupus erythematosus (SLE), a complex autoimmune disease. The proposed genes include members of the type I interferon (IFN) pathway and genes involved in immunological defense functions. Our aim was to systematically replicate 6 such genes, TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2. METHODS: Single-nucleotide polymorphisms in TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2 were genotyped in 277 SLE patients and 356 healthy controls from Finland, giving a power of 42%-70% for different genes at published allele frequencies. RESULTS: Significant association was seen for rs2304256 (p = 0.0001) and rs12720270 (p = 0.0031) in TYK2 and rs10954213 (p = 0.0043) in IRF5 in our samples, but not for the other genes. We found evidence for genetic interaction (p = 0.014) between rs2304256 in TYK2 and rs10954213 in IRF5, both members of the type I IFN pathway, strengthening the role of the type I IFN pathway in the pathogenesis of SLE. CONCLUSION: The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for SLE, but our lack of replication does not exclude effects of the other genes studied.


Assuntos
Epistasia Genética/imunologia , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , TYK2 Quinase/genética , Adolescente , Adulto , Idoso , Antígenos CD/genética , Proteínas Reguladoras de Apoptose/genética , Antígeno CTLA-4 , Criança , Feminino , Finlândia/epidemiologia , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Interferon Tipo I/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1 , Receptores de IgG/genética , Fatores de Risco , Adulto Jovem
19.
PLoS One ; 4(12): e8037, 2009 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-19997561

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families. PRINCIPAL FINDINGS: Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P -value = 0.001, Odds Ratio (OR) = 1.292, 95% CI 1.103-1.513) and rs2297926 (P -value = 0.003, OR = 1.349, 95% CI 1.109-1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans. SIGNIFICANCE: Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Moléculas de Adesão de Célula Nervosa/genética , Linhagem Celular , Cromossomos Humanos Par 14/genética , Citocinas/genética , Citocinas/metabolismo , Proteínas Ligadas por GPI , Regulação da Expressão Gênica , Ligação Genética , Loci Gênicos/genética , Humanos , Lúpus Eritematoso Sistêmico/patologia , Monócitos/metabolismo , Moléculas de Adesão de Célula Nervosa/química , Razão de Chances , Filogenia , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos
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