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2.
PLoS One ; 15(7): e0235295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687504

RESUMO

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.


Assuntos
Dermatite Atópica/genética , Inflamação/genética , Queratina-14/genética , Proteínas do Tecido Nervoso/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Animais , Apoptose/genética , Artrite/genética , Artrite/patologia , Dermatite Atópica/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Imunoglobulina E/genética , Inflamação/patologia , Integrases/genética , Interleucina-18/genética , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , NF-kappa B/genética , Fenótipo , Transdução de Sinais
3.
J UOEH ; 42(2): 167-173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32507840

RESUMO

The distinction between bacterial infectious and noninfectious arthritis is typically challenging in the early stages; however, it is critical for treatment decision making. Here, we investigated the diagnostic relevance of alpha- and beta-defensin levels in serum and synovial fluid as biomarkers of joint infection in patients presenting with fever and arthritis. The study included 12 patients who presented with fever (≥37°C) and arthritis (pain in the knee or hip joint). The diagnostic criteria for periprosthetic joint infection proposed by the Musculoskeletal Infection Society were used to detect joint infection and categorize the patients into infection and non-infection groups. Alpha-defensin-1 and beta-defensin-3 levels in serum and synovial fluid were measured using enzyme-linked immunosorbent assay. No significant between-group difference was observed with respect to serum alpha-defensin-1 levels; however, synovial fluid alpha-defensin-1 levels were significantly higher in the infection group (33.6 ± 26.2 ng/ml) than in the non-infection group (0.9 ± 0.4 ng/ml). No significant between-group differences were observed with respect to serum or synovial fluid beta-defensin-3 levels. Furthermore, synovial fluid alpha-defensin-1 levels were increased in patients without prosthesis in the infection group. In conclusion, in patients with fever and arthritis, synovial fluid alpha-defensin-1 levels were significantly higher in patients with infectious arthritis than in those with noninfectious arthritis. Therefore, synovial fluid alpha-defensin-1 levels is a useful diagnostic marker for joint infection.


Assuntos
Artrite/diagnóstico , Líquido Sinovial/química , alfa-Defensinas/análise , Biomarcadores/análise , Humanos
6.
Medicine (Baltimore) ; 99(19): e20077, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384476

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) for treatment of end-stage post-traumatic arthritis (PTA) has specific technical difficulties and complications. The aim of this study was to examine the outcome of TKA after PTA and to compare it with a cohort osteoarthritis (OA). METHODS: A retrospective review of patients undergoing primary TKA at a single university hospital from 2013 to 2016 was performed. A minimum follow-up of 4 years was required. Patients in the study group were matched 1:2 with patients in the cohort group based on the following criteria: age at time of TKA (±3 years), body mass index (±3 points), sex, and American Society of Anesthesiologists score (±1 point). Outcome measures included surgical time, intraoperative complications, Oxford Knee Score, range of motion, postoperative complications, and revision. RESULTS: This clinical trial is expected to determine whether PTA is associated with increased risks of complications and revision or reduced functional outcomes following TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5455).


Assuntos
Artrite/etiologia , Artrite/cirurgia , Artroplastia do Joelho , Traumatismos do Joelho/complicações , Osteoartrite do Joelho/cirurgia , Estudos de Coortes , Humanos , Estudos Retrospectivos , Resultado do Tratamento
9.
Isr Med Assoc J ; 22(5): 289-293, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32378820

RESUMO

BACKGROUND: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management. OBJECTIVES: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu. METHODS: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies. RESULTS: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2-6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed. CONCLUSIONS: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite/tratamento farmacológico , Síndrome de Behçet/tratamento farmacológico , Adalimumab/efeitos adversos , Adulto , Anti-Inflamatórios/efeitos adversos , Artrite/sangue , Artrite/etiologia , Síndrome de Behçet/sangue , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Citocinas/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
10.
BMJ ; 369: m1041, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457042

RESUMO

Lyme borreliosis is the most common vectorborne disease in the northern hemisphere. It usually begins with erythema migrans; early disseminated infection particularly causes multiple erythema migrans or neurologic disease, and late manifestations predominantly include arthritis in North America, and acrodermatitis chronica atrophicans (ACA) in Europe. Diagnosis of Lyme borreliosis is based on characteristic clinical signs and symptoms, complemented by serological confirmation of infection once an antibody response has been mounted. Manifestations usually respond to appropriate antibiotic regimens, but the disease can be followed by sequelae, such as immune arthritis or residual damage to affected tissues. A subset of individuals reports persistent symptoms, including fatigue, pain, arthralgia, and neurocognitive symptoms, which in some people are severe enough to fulfil the criteria for post-treatment Lyme disease syndrome. The reported prevalence of such persistent symptoms following antimicrobial treatment varies considerably, and its pathophysiology is unclear. Persistent active infection in humans has not been identified as a cause of this syndrome, and randomized treatment trials have invariably failed to show any benefit of prolonged antibiotic treatment. For prevention of Lyme borreliosis, post-exposure prophylaxis may be indicated in specific cases, and novel vaccine strategies are under development.


Assuntos
Antibacterianos/uso terapêutico , Doença de Lyme/tratamento farmacológico , Doença de Lyme/patologia , Acrodermatite/etiologia , Acrodermatite/patologia , Antibacterianos/administração & dosagem , Artrite/diagnóstico , Artrite/etiologia , Artrite/microbiologia , Grupo Borrelia Burgdorferi/genética , Eritema Migrans Crônico/etiologia , Eritema Migrans Crônico/microbiologia , Eritema Migrans Crônico/patologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Doença de Lyme/sangue , Doença de Lyme/epidemiologia , Masculino , América do Norte/epidemiologia , Síndrome Pós-Lyme/epidemiologia , Prevalência
15.
Nature ; 580(7801): 130-135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238926

RESUMO

Caspase-dependent apoptosis accounts for approximately 90% of homeostatic cell turnover in the body1, and regulates inflammation, cell proliferation, and tissue regeneration2-4. How apoptotic cells mediate such diverse effects is not fully understood. Here we profiled the apoptotic metabolite secretome and determined its effects on the tissue neighbourhood. We show that apoptotic lymphocytes and macrophages release specific metabolites, while retaining their membrane integrity. A subset of these metabolites is also shared across different primary cells and cell lines after the induction of apoptosis by different stimuli. Mechanistically, the apoptotic metabolite secretome is not simply due to passive emptying of cellular contents and instead is a regulated process. Caspase-mediated opening of pannexin 1 channels at the plasma membrane facilitated the release of a select subset of metabolites. In addition, certain metabolic pathways continued to remain active during apoptosis, with the release of only select metabolites from a given pathway. Functionally, the apoptotic metabolite secretome induced specific gene programs in healthy neighbouring cells, including suppression of inflammation, cell proliferation, and wound healing. Furthermore, a cocktail of apoptotic metabolites reduced disease severity in mouse models of inflammatory arthritis and lung-graft rejection. These data advance the concept that apoptotic cells are not inert cells waiting for removal, but instead release metabolites as 'good-bye' signals to actively modulate outcomes in tissues.


Assuntos
Apoptose/fisiologia , Microambiente Celular , Sistemas do Segundo Mensageiro/fisiologia , Animais , Artrite , Caspases/metabolismo , Linhagem Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Conexinas/metabolismo , Modelos Animais de Doenças , Rejeição de Enxerto , Humanos , Inflamação/genética , Transplante de Pulmão , Linfócitos/enzimologia , Linfócitos/metabolismo , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Fagócitos/metabolismo , Cicatrização/genética
16.
Z Rheumatol ; 79(5): 470-474, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32333101

RESUMO

This article describes the case of a 48-year-old female traveller returning from Bangladesh who presented with persisting pain and joint swelling due to chikungunya virus infection, which had persisted for months. Typical symptoms are a high fever and musculoskeletal disorders, which can last for months up to years. The chronic inflammatory form is treated similarly to those recommended for other chronic inflammatory joint diseases. Due to the increasing prevalence of the virus and its vectors as well as the unbroken travel activity, an increase in imported cases in Europe and establishment of the pathogen in southern Europe are to be expected.


Assuntos
Artrite/virologia , Febre de Chikungunya , Artrite/diagnóstico , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Vírus Chikungunya , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Viagem
20.
Nat Commun ; 11(1): 1658, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245954

RESUMO

The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the amplitude of intrinsic oscillators within macrophages and neutrophils is limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory regulatory T (Treg) cells within the joints show diurnal variation, with numbers peaking during the nadir of inflammation. Furthermore, the anti-inflammatory action of Treg cells on innate immune cells contributes to the night-time repression of inflammation. Treg cells do not seem to have intrinsic circadian oscillators, suggesting that rhythmic function might be a consequence of external signals. These data support a model in which non-rhythmic Treg cells are driven to rhythmic activity by systemic signals to confer a circadian signature to chronic arthritis.


Assuntos
Artrite/imunologia , Ritmo Circadiano/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Inflamação , Camundongos
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