RESUMO
The coexistence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in the same family is a rare event. We report a familial case originating from Sardinia of two siblings: one with NMOSD and one with MS. Human leukocyte antigen (HLA) typing showed that the two affected siblings were HLA-identical, sharing risk-increasing alleles, while a younger unaffected sister was haploidentical to her siblings but she also carried protective alleles. Our findings confirm the role of HLA in raising the risk to develop CNS inflammatory diseases and provide further knowledge on the relationship between NMOSD and MS.
Assuntos
Saúde da Família , Esclerose Múltipla , Neuromielite Óptica , Adulto , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Potenciais Evocados Visuais/genética , Feminino , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Itália/epidemiologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/genética , Esclerose Múltipla/fisiopatologia , Mutação/genética , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/genética , Neuromielite Óptica/fisiopatologia , Medula Espinal/diagnóstico por imagemRESUMO
Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco de Sangue Periférico , Sirolimo/uso terapêutico , Linfócitos T Reguladores/imunologia , Administração Oral , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Plaquetas/citologia , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Criança , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Neutrófilos/citologia , Estudos Prospectivos , Rituximab , Linfócitos T/imunologia , Doadores de Tecidos , Condicionamento Pré-Transplante , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto JovemRESUMO
The Island of Martin Garcia is located in the Upper Río de la Plata, to the south of mouth the Uruguay River. The aim of the present study was to analyse the biodiversity of the island freshwater mollusks and their relationships to environmental variables. Twelve sampling sites were selected, five were along the littoral section of the island and seven were Inland ponds. Seven major environmental variables were measured: water and air temperature, percentage of oxygen saturation, dissolved oxygen, electrical conductivity, total dissolved solids and pH. Twenty-seven mollusk species were found, Antillorbis nordestensis, Biomphalaria tenagophila tenagophila , B. t. guaibensis, B. straminea, B. peregrina, Drepanotrema kermatoides, D. cimex, D. depressissimum, Chilina fluminea, C. rushii, C. megastoma, Uncancylus concentricus, Hebetancylus moricandi, Stenophysa marmorata, Heleobia piscium, H. parchappii, Potamolithus agapetus, P. buschii, P. lapidum, Pomacea canaliculata, P. megastoma, Asolene platae, Corbicula fluminea, Eupera platensis, Pisidium sterkianum, P. taraguyense and Limnoperna fortunei. UPGMA clustering of species based on their occurrence in different ecological conditions revealed two main species groups. The Canonical Correspondence Analysis suggests that the species distribution is related to the physico-chemical condition of water. Axis two of the ordination diagram displayed the approximately 95.6% of the correlation between species and environmental variables. Dissolved oxygen, conductivity, water temperature and pH showed the highest fluctuations during the sampling period. The species richness (S) showed relationships mainly with water temperature and conductivity. The biodiversity of the gastropods and bivalves from Martín García Island amounts to up to 26 species. Among the Gastropoda, the Planorbidae family made the most sizeable contribution. The Lithogliphidae P. agapetus (26.28%) and P. buschii (9.50%) showed the highest relative frequencies of occurrence within the littoral environments, while the Planorbidae D. cimex (23.83%) and D. kermatoides (11.59%) likewise did so in the inland ponds.
Assuntos
Bivalves/classificação , Ecossistema , Gastrópodes/classificação , Rios/química , Animais , Argentina , Biodiversidade , Densidade Demográfica , TemperaturaRESUMO
Variations of the main immunoglobulin fractions in CSF were studied in 79 children with various inflammatory processes of CNS (purulent and viral meningitis, post-infectious meningoencephalitis, polyradiculoneuritis, etc). This study was extended to a group of non-inflammatory neurological diseases. Increased values of CSF immunoglobulins (especially IgG and IgA) were found in the group of purulent meningitis and in the group of post-infectious meningoencephalitis. IgM was detected in very few cases. Generally, a correlation was observed between highest concentrations of CSF immunoglobulins and degree of meningeal inflammatory response, even if this was a component of other neurological diseases. It is suggested that the rise of CSF IgG and IgA may depend upon the CSF-blood barrier damage, as it occurs in most inflammatory diseases studied. On the contrary, a production "in situ" of CNS could explain the presence of cerebrospinal IgM.