RESUMO
Pemphigus vulgaris is a severe, socially significant autoimmune disease associated with autoantibodies to the desmoglein 3 antigen. The disease affects all age groups, beginning at 18 years of age; the mortality rate of pemphigus can reach as high as 50%, depending on a patient's age and a number of other factors. There is no highly selective or personalized therapy for pemphigus vulgaris at the moment. One of the well-known therapeutic approaches to the disease is to use rituximab, an anti-CD20 antibody that can help achieve B cell depletion in peripheral blood. To solve the problem of nonspecific elimination of B cells in patients with pemphigus vulgaris, it is reasonable to use specific immunoligands, their choice being based on an assessment of the level of autoantibodies specific to each of the fragments of desmoglein. In this work, the proportion of autoreactive B cells in patients diagnosed with pemphigus vulgaris is found to be 0.09-0.16%; a positive correlation was revealed between the antibody level and the number of autoreactive B cells to various fragments of desmoglein.
RESUMO
A method for the analysis of the epitope specificity of auto-reactive antibodies to desmoglein 3 (Dsg3) using competitive ELISA has been developed. It is based on a two-stage solid-phase ELISA with initial "depletion" of auto-reactive antibodies against the studied epitope and subsequent quantitative assessment of antibodies against full-length extracellular domain Dsg3. The proposed approach for assessing the specificity of the autoimmune response in patients with pemphigus vulgaris can provide in the future the possibility to personalize the therapy using plasmapheresis by preliminary selection of the antigenic composition of the extracorporeal immunosorbent.
Assuntos
Autoanticorpos/imunologia , Desmogleína 3/imunologia , Pênfigo/imunologia , Animais , Especificidade de Anticorpos , Autoanticorpos/sangue , Autoanticorpos/metabolismo , Células CHO , Cricetulus , Desmogleína 3/química , Desmogleína 3/metabolismo , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Espaço Extracelular , Humanos , Pênfigo/sangue , Pênfigo/patologia , Fragmentos de Peptídeos/imunologia , Domínios Proteicos/imunologiaRESUMO
Using the recombinant second fragment of the extracellular domain (EC2) of human desmoglein type 3 (Dsg3) as an affinity ligand, an immunosorbent was obtained that selectively binds autoreactive antibodies to this domain from the immune sera of patients with pemphigus. The EC2 protein was obtained in the form of a fusion protein with the Fc-fragment of human IgG1. The production was carried out in CHO cells using the method of transient expression.
Assuntos
Autoanticorpos/imunologia , Desmogleína 3/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Pênfigo/imunologia , Proteínas Recombinantes de Fusão/imunologia , Autoanticorpos/sangue , Matriz Extracelular/imunologia , Humanos , Pênfigo/sangue , Pênfigo/patologiaRESUMO
A hemispheric interaction during verbal creative thinking was studied by the analysis of EEG coherence in the band of 4-30 Hz. 18 males and 21 females (right-handed university students) participaited in the experiments. Independently of gender, the performance of Remote Associates Task was accompanied by an increase in coherence in the theta1 and beta2 frequency bands as compared to the states of rest and the letter-fluency and simple associate's tasks. Successful search for original word associates as compared to generation of standard words was accompanied by a local increase in the interhemispheric coherence of the beta2 rhythm mostly in the parietotemporal cortex. In creative men, the increase in the hemispheric interaction efficient for a search for original words was focused in the frontal and temporal loci of the right hemisphere and in the left occipital locus, whereas in creative women the increase in coherence was observed in the left frontal and temporal regions. Creative men differed from non-creative ones by higher inter- and intrahemispheric coherence and were similar to women in the level of hemispheric interaction. The cortical distribution of foci of interhemispheric coherence reactivity indicates that the cortical organization of verbal functions depends on both sex and creativity of men and women.
Assuntos
Córtex Cerebral/fisiologia , Criatividade , Eletroencefalografia , Adolescente , Adulto , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Fatores Sexuais , Aprendizagem VerbalRESUMO
The routine methods X-ray study and computed tomography (CT) were compared in a group of patients engaged in fireproof industry. CT yields valuable additional data in early silicotuberculosis, which makes it possible to follow the extent of a silicotuberculous process more completely, to make a better diagnosis of nodal and focal shadows, to identify small decay cavities in the foci and infiltrates. CT is the method of choice in following up patients with silicotuberculosis.