RESUMO
We demonstrate that patients with primary Sjögren's syndrome (pSS) produce functional IgG autoantibodies that interact with the glandular M(3) muscarinic acetylcholine receptors (mAChRs). These autoantibodies act as a partial muscarinic agonist, increasing prostaglandin E(2) (PGE(2)) and cyclic AMP production through modifying Na(+)/K(+)-ATPase activity, but also interfere with the secretory effect of the parasympathetic neurotransmitter. The IgG from patients with pSS has two effects on the submandibular gland. On the one hand, it may act as an inducer of the proinflammatory molecule (PGE(2)) that, in turn, inhibits Na(+)/K(+)-ATPase activity. On the other hand, it plays a role in the pathogenesis of dry mouth, abolishing the Na(+)/K(+)-ATPase inhibition and the net K(+) efflux stimulation of the salivary gland in response to the authentic agonist pilocarpine, decreasing salivary fluid production.
Assuntos
Autoanticorpos/imunologia , AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Imunoglobulina G/imunologia , Agonistas Muscarínicos/imunologia , Receptor Muscarínico M3/imunologia , Síndrome de Sjogren/imunologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Glândula Submandibular/enzimologia , Adulto , Animais , Células Cultivadas , Feminino , Humanos , Fatores Imunológicos/imunologia , Mediadores da Inflamação/imunologia , Ceratoconjuntivite Seca/imunologia , Masculino , Pessoa de Meia-Idade , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Pilocarpina/farmacologia , Piperidinas/farmacologia , Pirenzepina/farmacologia , Potássio/metabolismo , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/metabolismo , Tropicamida/farmacologia , Xerostomia/imunologiaRESUMO
Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in many regions of the world, including Brazil, and has been associated to several immunological manifestations such as arthritis, uveitis, dermatitis and Sjögren's syndrome. This study was intended to evaluate the frequency of autoantibodies in patients infected with HTLV-1 and manifesting keratoconjunctivitis sicca (KCS). HTLV-1 patients with KCS, enrolled in a reference ambulatory of the city of Salvador, were tested for autoantibodies such as antinuclear antibodies, rheumatoid factor, anti-SSA/Ro and anti-SSB/La. Two comparison groups were also included: (a) HTLV-1 patients without KCS and (b) seronegative patients with KCS. Correlation of proviral load (PVL) in HTLV-1 patients with presence or absence of KCS was also assessed. No autoantibodies were detected in HTLV-1 patients with KCS. The PVL of HTLV-1 patients was higher in patients with KCS without other clinical manifestations customarily associated to HTLV-1. In conclusion, in this study, no changes were observed in humoral immunity concerning production of certain autoantibodies in HTLV-1-infected patients with KCS, which suggests that other mechanisms may be involved in the pathogenesis of this manifestation. Additionally, PVL may be a marker of KCS development in these patients.
Assuntos
Autoanticorpos/sangue , Infecções por HTLV-I/complicações , Ceratoconjuntivite Seca/imunologia , Ceratoconjuntivite Seca/virologia , Adulto , Idoso , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/sangue , Autoanticorpos/análise , Biomarcadores/análise , Biomarcadores/sangue , Brasil , Estudos de Coortes , Feminino , Humanos , Imunidade Humoral/fisiologia , Ceratoconjuntivite Seca/sangue , Masculino , Pessoa de Meia-Idade , Provírus/imunologia , Fator Reumatoide/análise , Fator Reumatoide/sangue , Ribonucleoproteínas/imunologia , Carga ViralRESUMO
PURPOSE: To verify the occurrence of keratoconjunctivitis sicca (KCS) and human T-cell lymphotropic virus type 1 (HTLV-1) associated uveitis (HAU) and to evaluate the immunologic status related to HTLV-1. DESIGN: Cross-sectional study. METHODS: Ophthalmic examination (both eyes) and immunophenotyping of peripheral blood lymphocytes were performed in 207 infected asymptomatic blood donors (AS), 55 controls (NI), and 55 patients with HTLV-1 associated myelopathy (HAM/TSP). Examiner was masked to patient's serologic status. RESULTS: KCS was more frequent in HAM/TSP (30/55, 54.5%) than in NI and AS (07/55, 12.7% and 42/207, 20.3%, respectively). Presence of lacrimal hyposecretion in KCS individuals was higher in the HAM/TSP group (P < .001) as compared with NI and AS. HAU was found in 1/55 (1.82%) of HAM/TSP patients and 4/207 (1.93%) of HTLV-1 seropositive donors. Higher levels of activated CD4(+) and CD8(+) T cells were observed in HAM/TSP. Patients with HAU displayed higher percentage of both CD4(+) HLA-DR(+) and CD8(+)HLA-DR(+) when compared with NI and AS without HAU. CONCLUSIONS: Patients with HAM/TSP manifested more ophthalmologic symptoms than asymptomatic HTLV-1-infected individuals, with significantly higher KCS and immunologic alterations. Levels of activated CD8+ T cells could be used as a prognosis marker of inflammatory disease manifestation to follow-up AS individuals.
Assuntos
Biomarcadores , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Ceratoconjuntivite Seca/etiologia , Paraparesia Espástica Tropical/complicações , Uveíte/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos Transversais , Feminino , Antígenos HLA-DR/imunologia , Humanos , Imunofenotipagem , Ceratoconjuntivite Seca/imunologia , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Uveíte/imunologiaRESUMO
The objective of this study is to describe the clinical and immunological aspects observed in patients with both "tropical spastic paraparesis/HTLV-I associated myelopathy" (TSP/HAM) and ocular dryness. In 10 such patients clinical and biological examinations completed with a biopsy of secondary salivary glands were performed to assess the etiology of the ocular dryness. According to the Chisholm's scale, 70% of the patients had a biopsy grade 3 or grade 4. Polyclonal hypergammaglobulinemia was found in 90% of patients and lymphocytic alveolitis in 80%. Three patients had past medical history of chronic uveltis. All the findings were compatible with Sjögren's syndrome, however no characteristic immunological disorders were found. Antinuclear antibodies and rheumatoid factor proved negative in all cases.