RESUMO
The MHC class I protein HLA-B27 is strongly associated with susceptibility to spondyloarthropathies and can cause arthritis when expressed in rats and mice, implying a direct role in disease pathogenesis. A prominent hypothesis to explain this role suggests that the unique peptide binding specificity of HLA-B27 confers an ability to present arthritogenic peptides. The B pocket, a region of the peptide binding groove that is an important determinant of allele-specific peptide binding, is thought to be critical for arthritogenicity. However, this hypothesis remains unproven. We show that in addition to its role in peptide selection, the B pocket causes a portion of the pool of assembling HLA-B27 heavy chains in the endoplasmic reticulum to misfold, resulting in their degradation in the cytosol. The misfolding phenotype is corrected by replacing the HLA-B27 B pocket with one from HLA-A2. Our results suggest an alternative to the arthritogenic peptide hypothesis. Misfolding and its consequences, rather than allele-specific peptide presentation, may underlie the strong link between the HLA-B27 B pocket and susceptibility to spondyloarthropathies.
Assuntos
Artrite/imunologia , Antígeno HLA-B27/metabolismo , Fragmentos de Peptídeos/metabolismo , Dobramento de Proteína , Espondilite/imunologia , Substituição de Aminoácidos , Apresentação de Antígeno , Artrite/etiologia , Artrite/metabolismo , Citosol/imunologia , Citosol/metabolismo , Suscetibilidade a Doenças , Antígeno HLA-B27/química , Antígeno HLA-B27/fisiologia , Humanos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/fisiologia , Ligação Proteica/imunologia , Espondilite/etiologia , Espondilite/metabolismoAssuntos
Artrite/imunologia , Antígeno HLA-B27/imunologia , Espondilite/imunologia , Antígenos de Bactérias/imunologia , Artrite/microbiologia , Artrite Reativa/imunologia , Artrite Reativa/microbiologia , Bactérias/imunologia , Antígeno HLA-B27/classificação , Antígeno HLA-B27/genética , Humanos , Espondilite/microbiologia , Subpopulações de Linfócitos T/imunologiaRESUMO
A conception of the adaptive functional dominant of the CNS is proposed for the description of general regularities of the course of patho- and sanogenesis in neurotramatologic patients. It was shown that the forming adaptive dominant is responsible for the development of adaptive processes in the posttraumatic period. The interaction of the functional dominant and adaptive potential of sanogenesis leads to the course of the disease with the natural outcome as recovery, complication or lethal outcome.
Assuntos
Adaptação Fisiológica , Lesões Encefálicas/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Atividade Nervosa Superior , Reflexo , Lesões Encefálicas/imunologia , Sistema Nervoso Central/imunologia , Humanos , Osteocondrite/imunologia , Osteocondrite/fisiopatologia , Psiconeuroimunologia , Espondilite/imunologia , Espondilite/fisiopatologia , Fatores de TempoRESUMO
Bath therapy was assigned to 300 patients with primary hypothyroidism, chronic venous insufficiency of the legs, neurologic symptoms of lumbar osteochondrosis. Fresh, siliceous, siliceous carbon-dioxide and carbon-dioxide waters were tested comparatively. It is reported that siliceous baths with threshold silicon compounds concentration 50 mg/l had the effect similar to that of fresh-water baths. Indications have been specified for introduction of carbon dioxide and siliceous carbon dioxide baths in the diseases studied.
Assuntos
Banhos/métodos , Silício/uso terapêutico , Dióxido de Carbono/uso terapêutico , Doença Crônica , Estudos de Avaliação como Assunto , Água Doce , Humanos , Hipotireoidismo/imunologia , Hipotireoidismo/fisiopatologia , Hipotireoidismo/reabilitação , Vértebras Lombares , Osteocondrite/imunologia , Osteocondrite/fisiopatologia , Osteocondrite/reabilitação , Espondilite/imunologia , Espondilite/fisiopatologia , Espondilite/reabilitação , Insuficiência Venosa/imunologia , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/reabilitaçãoRESUMO
The IgA and IgG antibody response to plasmid-encoded outer membrane proteins was studied in 59 patients with yersinia-associated spondylarthropathy during 15 months of follow-up. Initially, all patients had specific IgA and IgG antibodies to the 36 and 46 kDa and 30% also to the 26 and 58 kDa released proteins, which correlated with the finding of virulent Yersinia bacilli in intestinal biopsies. IgA disappeared in 69% of untreated patients after nine months and persisted in 31% after one year. IgA disappeared within three to six months in 81% of the patients treated with antibiotics for four to six weeks and persisted in 6% after one year (p less than 0.002). IgG antibodies to the 36 and 46 kDa outer membrane proteins persisted in 80% of all patients. Disappearance of IgA was coupled with disappearance of yersinia from intestinal biopsies.