RESUMO
Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both articular and extra-articular tissues. Galectins have been reported to play central roles in RA and its experimental animal models. In this perspective article we present new data highlighting the regulated expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in sera from RA patients under disease-modifying anti-rheumatic drugs (DMARDs) and/or corticoid treatment in the context of a more comprehensive discussion that summarizes the roles of galectins in joint inflammation. We found that Gal-1 levels markedly increase in sera from RA patients and positively correlate with erythrocyte sedimentation rate (ERS) and disease activity score 28 (DAS-28) parameters. On the other hand, Gal-3 is downregulated in RA patients, but positively correlates with health assessment questionnaire parameter (HAQ). Finally, by generating receiver-operator characteristic (ROC) curves, we found that Gal-1 and Gal-3 serum levels constitute good parameters to discriminate patients with RA from healthy individuals. Our findings uncover a differential regulation of Gal-1 and Gal-3 which might contribute to the anti-inflammatory effects elicited by DMARDs and corticoid treatment in RA patients.
Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/etiologia , Biomarcadores , Galectina 1/sangue , Galectina 3/sangue , Animais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.
Assuntos
Artrite Reumatoide/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 1/genética , Antígenos HLA/genética , Feminino , Genótipo , Humanos , Indígenas Sul-Americanos , América Latina , Masculino , Análise de Sequência com Séries de OligonucleotídeosAssuntos
Infecções Comunitárias Adquiridas/complicações , Unidades de Terapia Intensiva , Doenças Reumáticas/diagnóstico , APACHE , Adulto , Argentina , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The purpose of the following study was to analyze maternal and fetal outcomes in pregnant patients with systemic lupus erythematosus (SLE) and the influence of SLE exacerbations on those pregnancies. Seventy-two pregnancies in 61 SLE patients treated between January 1986 and February 2004 in Hospital de Clínicas "José de San Martin" were reviewed retrospectively. Patient age was 28.1 +/- 6.2 years (mean+/-standard deviation [SD]). Mean SLE duration was 4.5 +/- 3.2 years (range 6 months-10 years). No patient acquired the disorder during gestation. Four (5.5%) patients had signs of active disease at the beginning of her pregnancy. Sixteen patients, accounting for 20 pregnancies, had a history of lupus nephritis. Nine patients met secondary antiphospholipid syndrome criteria and had 13 pregnancies. There were 14 exacerbations of the disease during pregnancy (19.4%), with most flares being mild. The most common obstetric complications were gestational hypertension in 15 pregnancies (20.8%) and preeclampsia in 8 pregnancies (11%). Forty-six percent of pregnancies ended in preterm deliveries. There were 62 live births (1 twin birth; 85%), 6 stillbirths (8%), and 5 spontaneous abortions (7%). Thirty-nine percent of newborns had low birth weight. Adequate pregnancy follow-up and delivery care by an interdisciplinary team in Argentine SLE patients with no pre-gestational preparation resulted in maternal and fetal outcomes similar to those seen in world reference centers.
Assuntos
Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Lúpus Eritematoso Sistêmico/fisiopatologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Adulto , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Argentina/epidemiologia , Comorbidade , Feminino , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Prednisona/uso terapêutico , Gravidez , Estudos RetrospectivosAssuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/etiologia , Adulto , Síndrome Antifosfolipídica/tratamento farmacológico , Audiometria , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Medição de Risco , Resultado do TratamentoRESUMO
Pachydermoperiostosis or primary hypertrophic osteoarthropathy is a rare disease characterized by cutaneous and osteoarthicular involvement. We describe two patients with finger clubbing, watch crystal nails, bones thickenings, arthritis and different grades of skin affection, without other clinical manifestations. Both did not know of having relatives with the same alterations. Radiological studies of the affected areas showed periostosis. Because of normal laboratory results and chest radiography plus the absence of other underlying causes, diagnosis of primary hypertrophic osteoarthropathy was made.
Assuntos
Osteoartropatia Hipertrófica Primária/patologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Osteoartropatia Hipertrófica Primária/diagnóstico por imagem , Osteoartropatia Hipertrófica Primária/terapia , RadiografiaRESUMO
La paquidermoperiostosis u osteoartropatía hipertrófica primaria es una rara enfermedadcaracterizada por compromiso cutáneo y osteoarticular. Comunicamos dos casos que presentabanhipocratismo digital, uñas en vidrio de reloj, agrandamiento óseo, tumefacción articular y diferentes grados deafectación cutánea, sin otros hallazgos clínicos relevantes. Ambos desconocían antecedentes familiares similares.El estudio radiográfico de las zonas comprometidas mostró periostosis. Con resultados de laboratorio yradiografía de tórax normales, y ausencia de evidencia clínica de otra enfermedad subyacente, se realizó diagnósticode osteoartropatía hipertrófica primaria.
Pachydermoperiostosis orprimary hypertrophic osteoarthropathy is a rare disease characterized by cutaneous and osteoarthicularinvolvement. We describe two patients with finger clubbing, watch crystal nails, bones thickenings,arthritis and different grades of skin affection, without other clinical manifestations. Both did not know of havingrelatives with the same alterations. Radiological studies of the affected areas showed periostosis. Because ofnormal laboratory results and chest radiography plus the absence of other underlying causes, diagnosis of primaryhypertrophic osteoarthropathy was made.