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1.
Cell Host Microbe ; 26(1): 100-113.e8, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31227334

RESUMO

Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen ß2-glycoprotein I (ß2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-ß2GPI IgG autoantibodies. R. int immunization of mice induced ß2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human ß2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Autoimunidade , Linfócitos B/imunologia , Clostridiales/imunologia , Reações Cruzadas , Linfócitos T/imunologia , Adulto , Idoso , Animais , Síndrome Antifosfolipídica/patologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Imunoglobulina G/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Adulto Jovem , beta 2-Glicoproteína I/imunologia
2.
Foot Ankle Int ; 37(7): 776-81, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27026727

RESUMO

BACKGROUND: The purpose of this study was to assess the effect of insurance type (Medicaid, Medicare, and private insurance) on access to foot and ankle surgeons for total ankle arthroplasty. METHODS: We called 240 foot and ankle surgeons who performed total ankle arthroplasty in 8 representative states (California, Massachusetts, Ohio, New York, Florida, Georgia, Texas, and North Carolina). The caller requested an appointment for a fictitious patient to be evaluated for a total ankle arthroplasty. Each office was called 3 times to assess the responses for Medicaid, Medicare, and BlueCross. From each call, we recorded appointment success or failure and any barriers to an appointment, such as need for a referral. RESULTS: Patients with Medicaid were less likely to receive an appointment compared to patients with Medicare (19.8% vs 92.0%, P < .0001) or BlueCross (19.8% vs 90.4%, P < .0001) and experienced more requests for referrals compared to patients with Medicare (41.9% vs 1.6%, P < .0001) or BlueCross (41.9% vs 4%, P < .0001). Waiting periods were longer for patients with Medicaid compared to those with Medicare (22.6 days vs 11.7 days, P = .004) or BlueCross (22.6 days vs 10.7 days, P = .001). Reimbursement rates did not correlate with appointment success rate or waiting period. CONCLUSION: Despite the passage of the PPACA, patients with Medicaid continue to have difficulty finding a surgeon who will provide care, increased need for a primary care referral, and longer waiting periods for appointments. LEVEL OF EVIDENCE: Level II, prognostic study.


Assuntos
Articulação do Tornozelo/cirurgia , Artroplastia/métodos , Acessibilidade aos Serviços de Saúde/economia , Cobertura do Seguro/economia , Patient Protection and Affordable Care Act/economia , Articulação do Tornozelo/fisiopatologia , Artroplastia/economia , Medicaid , Medicare , Estados Unidos
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