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1.
Exp Dermatol ; 31(5): 753-763, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34890074

RESUMO

TNFα-inhibitor-induced psoriasis is mediated by the type-I interferon pathway, of which IFNα, LL37 and IL-36γ are major players. A subset of patients treated with TNFα inhibitors develop small plaque psoriatic lesions. Small plaque psoriasis is similarly observed in patients on immune checkpoint inhibitors (ICI), and with concurrent systemic lupus erythematosus (SLE) or positive antinuclear antibody (ANA). Small plaque psoriasis is also the predominant phenotype in Asian populations. The association between small plaque psoriasis morphology in various clinical scenarios and the type-I interferon pathway has not been previously studied. A cross-sectional study was conducted of patients who developed small plaque psoriasis and had a biopsy for diagnostic clarification between 2009 and 2017. We obtained skin specimens from 14 adults with small plaque psoriasis: four patients taking anti-TNFα treatment, four patients with antecedent SLE, three patients with concurrent ANA positivity and three patients taking ICI. Controls included three patients with chronic plaque psoriasis. Histology confirmed psoriasiform epidermal hyperplasia with focal lichenoid and spongiotic features. Immunohistochemical analysis revealed higher expression of IFNα-induced MXA, LL37 and IL-36γ in all clinical scenarios of small plaque psoriasis compared to chronic plaque psoriasis. There was decreased CD8 T-cell migration to the epidermis and variability in the number of LAMP3+ cytoplasmic dendritic cells in the dermis of small plaque psoriasis. The findings suggest that small plaque psoriasis is a unique type of psoriasis with a distinct morphology and immune-phenotype, primarily mediated by the type-I interferon pathway. Associating morphology and disease pathogenesis may help identify therapeutic targets for better disease control.


Assuntos
Interferon Tipo I , Lúpus Eritematoso Sistêmico , Psoríase , Estudos Transversais , Humanos , Psoríase/metabolismo , Fator de Necrose Tumoral alfa
2.
J Immunol ; 203(9): 2443-2450, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578270

RESUMO

Skin tissue resident memory T cells (TRM) provide superior protection to a second infection. In this study, we evaluated the use of topical CpG oligodeoxynucleotide (ODN) as adjuvant to generate skin TRM in mice. Topical or s.c. CpG ODN adjuvant administration at the time of a s.c. Ag injection led to an accumulation of CD103- CD8 T cells in the epidermis. However, only mice with CpG ODN administered topically had significant numbers of CD103+ Ag-specific CD8 T cells persisting in the local epidermal skin, enhanced circulating memory cells in the blood, and showed protection from intradermal challenge with melanoma cells. Generation of Ag-specific CD8 T cells was dependent on TLR9 expression on hematopoietic cells and partially dependent on receptor expression on stromal cells. Topical challenge of immunized mice at a distal site led to significant expansion of Ag-specific T cells in the blood and accumulation in the challenged skin. We demonstrate that local and systemic T cell memory can be generated with topical CpG ODN at the time of s.c. immunization, suggesting a new method of enhancing current vaccine formulations to generate tissue TRM.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Memória Imunológica , Oligodesoxirribonucleotídeos/administração & dosagem , Pele/imunologia , Linfócitos T/fisiologia , Vacinação , Animais , Linhagem Celular Tumoral , Imunidade Inata , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Receptor Toll-Like 9/fisiologia
3.
Pediatr Dermatol ; 37(4): 742-744, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32202653

RESUMO

Cutaneous manifestations are common in monogenic immune disorders, including both infectious and non-infectious etiologies. We report follow-up of a case initially published in Pediatric Dermatology in 2001 of a 13-year-old boy with a history of inflammatory skin lesions and neutropenia who developed neutrophilic dermatoses precipitated by G-CSF. Whole exome sequencing performed at 36 years of age revealed a gain-of-function mutation in the WAS gene, leading to a diagnosis of X-linked neutropenia. This case report provides closure on a decades-long diagnostic odyssey and underscores the importance of genetic sequencing in patients who present with unusual dermatologic findings.


Assuntos
Neutropenia , Dermatopatias , Abscesso/diagnóstico , Abscesso/genética , Adolescente , Criança , Humanos , Masculino , Neutropenia/diagnóstico , Neutropenia/genética , Sequenciamento do Exoma
4.
J Cutan Med Surg ; 23(6): 595-601, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31378082

RESUMO

BACKGROUND AND OBJECTIVE: East Asians exposed to the urate-lowering drug allopurinol have a predilection for severe cutaneous drug reactions such as drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Screening is recommended in patients of East Asian descent for the presence of HLA-B*58:01 prior to allopurinol initiation to avoid these complications. Utilization rates of the HLA-B*58:01 predictive screening test within the Greater Vancouver area, which has a population composed of 40.1% people of East Asian descent, are unknown. MEASURES: We identified cases of DRESS or SJS/TEN due to allopurinol using the Vancouver General Hospital dermatology consult service database. We next compared the frequency in which the HLA-B*58:01 screening test was ordered since 2012 to the estimated frequency of new prescriptions for allopurinol prescribed for the management of gout among the East Asians. RESULTS: We report 5 cases of East Asian patients exposed to allopurinol for management of gout between 2012 and 2016, who developed DRESS (4 patients) or SJS/TEN (1 patient). All were of HLA-B*58:01 genotype, representing preventable cases. The HLA-B*58:01 test was ordered 6 times in 2012, whereas the estimated number of new cases of allopurinol-prescribed gout among patients of East Asian descent during that time period was 13. For 2012, testing was ordered for only 46% of at-risk patients. CONCLUSION: We continue to observe cases of severe cutaneous drug reactions among high-risk individuals due to allopurinol exposure. The HLA-B*58:01 screening test for allopurinol hypersensitivity is underutilized in our geographic area.


Assuntos
Alopurinol/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson , Idoso de 80 Anos ou mais , Alopurinol/uso terapêutico , Povo Asiático/genética , Colúmbia Britânica , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/genética , Síndrome de Hipersensibilidade a Medicamentos/prevenção & controle , Feminino , Genótipo , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Supressores da Gota/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/prevenção & controle
7.
Eur J Haematol ; 98(4): 378-387, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28005278

RESUMO

OBJECTIVE: To compare the clinical and laboratory features of IgG4-related disease (IgG4-RD) and lymphocyte-variant hypereosinophilic syndrome (L-HES), two rare diseases that often present with lymphadenopathy, gastrointestinal symptoms, eosinophilia, and elevated immunoglobulins/IgE. METHOD: Comparative case series of 31 patients with IgG4-RD and 13 patients with L-HES. RESULTS: Peripheral blood eosinophilia was present in eight of 31 patients with IgG4-RD compared to 13 of 13 patients with L-HES (median eosinophils 0.4 vs 7.0 giga/L, P=.001) and 12 of 20 patients with IgG4-RD had increased serum IgE compared to eight of 13 patients with L-HES, P=.930. Twenty-seven of 30 patients with IgG4-RD had elevated serum IgG4 compared to five of 12 patients with L-HES (median IgG4 9.6 g/L vs 0.80 g/L, P=.002). Flow cytometry demonstrated an aberrant T-cell phenotype in 7 of 23 patients with IgG4-RD and 13 of 13 patients with L-HES (P<.001). T-cell clonality by PCR was positive in 12 of 23 patients with IgG4-RD vs 10 of 13 patients with L-HES (P=.143). Patients in both groups received corticosteroids as first-line therapy. For refractory disease in IgG4-RD, rituximab was the most common steroid-sparing agent, whereas in L-HES, it was pegylated interferon-α-2a. CONCLUSION: The overlapping features of these two diseases with divergent treatment options demonstrate the importance of familiarity with both entities to optimize diagnosis and treatment.


Assuntos
Corticosteroides/administração & dosagem , Síndrome Hipereosinofílica , Imunoglobulina G/sangue , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Rituximab/administração & dosagem , Linfócitos T , Adulto , Idoso , Feminino , Humanos , Síndrome Hipereosinofílica/sangue , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem
9.
J Cutan Med Surg ; 21(6): 564-567, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28658971

RESUMO

Eruptive vellus hair cysts (EVHCs) often occur on the trunk and limbs. Facial involvement is uncommon. Autosomal dominant inheritance has been described, but associated extracutaneous anomalies have not. We describe a 4-patient kindred presenting with multiple facial EVHCs and an association of preauricular pits, lipomas, joint hypermobility, and cardiac defects. Histopathologic examination confirmed the diagnosis of EVHCs in 3 affected individuals. We propose that facial EVHCs may indicate the presence of an inherited autosomal dominant disorder with extracutaneous manifestations. Extracutaneous manifestations noted in the kindred have been sporadically described in association with steatocystoma multiplex (SM), a condition occasionally noted in the presence of EVHCs, further supporting an association between these disorders.


Assuntos
Cistos/complicações , Dermatoses Faciais/complicações , Doenças do Cabelo/complicações , Lipoma/complicações , Pré-Escolar , Anormalidades Craniofaciais/complicações , Anormalidades Craniofaciais/genética , Cistos/genética , Cistos/patologia , Dermatoses Faciais/genética , Dermatoses Faciais/patologia , Feminino , Doenças do Cabelo/genética , Doenças do Cabelo/patologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/genética , Humanos , Instabilidade Articular/complicações , Instabilidade Articular/genética , Lipoma/genética , Masculino , Linhagem
12.
Clin Immunol ; 154(1): 84-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24947953

RESUMO

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing pancreatic beta cells. There is now mounting evidence that pro-inflammatory pathways, which are mediated by T cells that secrete IL-17 and IFN-γ, play a critical role in the loss of beta cells. These data suggest that blockade of T cells that secrete IL-17 and IFN-γ may halt or reverse disease in subjects with recent-onset T1D. Agents to facilitate this approach are currently in clinical use. Ustekinumab, a humanized monoclonal antibody that targets the shared p40 subunit of IL-12 and IL-23, has been used for the treatment of psoriasis, an indication for which it has proven to be safe and effective. In this review, we summarize the evidence that supports a combined pathogenic role of IL-17 and IFN-γ in the development of T1D, with the aim of providing a rationale for testing agents such as ustekinumab for the treatment of T1D.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Sistemas de Liberação de Medicamentos , Interferon gama/imunologia , Interleucina-17/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Diabetes Mellitus Tipo 1/fisiopatologia , Humanos , Linfócitos T/imunologia , Ustekinumab
13.
J Am Acad Dermatol ; 71(5): 941-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25087214

RESUMO

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous reactions, typically to medications, that are associated with a high patient mortality. Controversy exists over which systemic treatments decrease mortality associated with SJS/TEN. OBJECTIVE: In this study we sought to determine whether intravenous immunoglobulin (IVIg) or cyclosporine use for SJS/TEN results in better patient outcomes. METHODS: We undertook a retrospective chart review of 71 patients admitted between 2001 and 2011 for SJS/TEN at a tertiary care center of which 64 cases were included in the data analysis. Predicted severity-of-illness score for TEN mortality was compared with actual mortality for patients treated with either cyclosporine or IVIg. RESULTS: Our cohort demonstrated a relative mortality benefit to the use of cyclosporine in the treatment of SJS/TEN with a standardized mortality ratio of 0.43, over the use of IVIg with a standardized mortality ratio of 1.43. LIMITATIONS: This is single-center retrospective study. CONCLUSIONS: The use of cyclosporine over IVIg may offer a greater mortality benefit in the treatment of SJS/TEN.


Assuntos
Ciclosporina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Adulto , Idoso , Ciclosporina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
14.
Adv Skin Wound Care ; 27(11): 518-24; quiz 525-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25325229

RESUMO

PURPOSE: The purpose of this learning activity is to provide information about the etiology and treatment of atrophie blanche. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Discuss the pathophysiology of atrophie blanche.2. Explore treatment options for livedoid vasculopathy. ABSTRACT: Atrophie blanche (AB) is a porcelain-white scar that may be seen at the base of a healed ulcer or in association with livedoid vasculopathy (LV). The term AB originally had been used synonymously with LV, whereas LV is a noninflammatory thrombotic condition presenting as either a primary or secondary event (often associated with coagulation).


Assuntos
Úlcera da Perna/etiologia , Úlcera da Perna/terapia , Livedo Reticular/etiologia , Livedo Reticular/terapia , Vasculite/complicações , Insuficiência Venosa/complicações , Cicatriz/patologia , Diagnóstico Diferencial , Educação Médica Continuada , Educação Continuada em Enfermagem , Feminino , Humanos , Úlcera da Perna/patologia , Livedo Reticular/patologia , Pessoa de Meia-Idade
15.
J Am Acad Dermatol ; 69(6): 1033-1042.e1, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24028907

RESUMO

Livedoid vasculopathy (LV) is a noninflammatory thrombotic condition presenting in a primary idiopathic or secondary subtype associated with abnormal coagulation factors. Different from atrophie blanche (AB), which is a clinical manifestation of certain scars, LV may have AB in combination with recurrent livedo reticularis with chronic and painful skin ulcers particularly around the ankle region, and at the back of the feet. Histology is characterized by segmental hyalinizing changes at the subintimal region of small dermal vessels with thrombotic occlusions. LV skin ulcers resolve with stellate, porcelain-white scars that need to be distinguished from similar changes seen with venous insufficiency. "Atrophie blanche" was originally used synonymously with "livedoid vasculopathy." AB describes spontaneously occurring porcelain-white skin areas with red dots that typically occur in the context of skin changes attributed to chronic venous insufficiency. The 2 forms of AB--(1) the LV-AB complex and (2) AB in the context of chronic venous insufficiency--are unrelated and require separate diagnostic and therapeutic approaches. Using a modified Delphi method, we have developed an international consensus document on the diagnosis and management of LV. Individual sections of this document provide advice on diagnosis and management of LV.


Assuntos
Livedo Reticular , Técnica Delphi , Humanos , Livedo Reticular/diagnóstico , Livedo Reticular/etiologia , Livedo Reticular/terapia , Guias de Prática Clínica como Assunto
16.
BMJ Open ; 13(11): e062306, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940157

RESUMO

OBJECTIVES: Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA). DESIGN: A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores. DATA SOURCES: Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials. ELIGIBILITY CRITERIA: Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes. DATA EXTRACTION AND SYNTHESIS: Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist. RESULTS: In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy. CONCLUSIONS: While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.


Assuntos
Antirreumáticos , Artrite Psoriásica , Humanos , Artrite Psoriásica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Metanálise em Rede , Antirreumáticos/uso terapêutico , Medidas de Resultados Relatados pelo Paciente
17.
Dermatol Ther (Heidelb) ; 13(4): 867-889, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36929121

RESUMO

BACKGROUND: Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. OBJECTIVES: We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?" METHODS: We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. RESULTS: We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. CONCLUSIONS: Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.


Patients with previously treated cancer have a higher chance of cancer recurrence compared with the general population. With cancer incidence rising worldwide, doctors across medical specialities will need to treat other medical conditions, including inflammatory diseases such as psoriasis, in these patients. Effective systemic therapies for psoriasis reduce immune cell activity. Accordingly, there are concerns that treatments for psoriasis could worsen cancer recurrence/progression and infectious complications. There is not enough quality evidence to make broad recommendations for treating other inflammatory conditions in patients with a history of cancer. To guide patient and doctor discussions, we asked: what are effective and safe treatments when patients with treated solid tumours need systemic therapy (pills or injections) for their psoriasis? We focused on patients with solid tumours and excluded blood and skin cancers. Our panel of experts, including 12 dermatologists and 3 medical oncologists, reviewed direct and indirect evidence to answer this question. Considering the totality of evidence reviewed, the expert panel drafted and rated their level of support for opinion statements on important considerations in treating patients with psoriasis who have a history of solid tumours. By making inferences on systemic psoriasis therapies in this heterogeneous population, we take the onus off individual physicians to review the indirect data. This process may help answer questions in other disease populations where direct evidence is scarce or absent. To support treatment decisions, doctors should have a guided conversation with the patient and their family on a case-by-case basis about the risks and benefits of treatment.

18.
Biol Blood Marrow Transplant ; 18(4): 546-56, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22178962

RESUMO

Cathepsin (Cathepsin) S, L, and B proteases mediate antigen presentation on major histocompatibility complex (MHC) class II by degrading the invariant chain Ii, which blocks peptide loading. The ability of the Cathepsin S inhibitor LHVS (morpholinurea-leucine-homophenylalanine-vinylsulfone phenyl) to impede antigen presentation has led its development as a therapy for autoimmune diseases. There is substantial evidence that donor T cell recognition of host minor histocompatibility antigens (miHA) and subsequent destruction of host tissue mediates graft-versus-host disease (GVHD). We hypothesized that enzymes involved in antigen presentation may play a role in the development of GVHD. Using the C57BL/6 → BALB.B minor mismatch acute GVHD (aGVHD) model, we found that the cathepsin S activity of spleens from allogenetically transplanted mice were significantly increased 1 week after transplantation compared with syngeneic mice. Although LHVS decreased T cell priming responses against both single OVA antigen and miHA in vitro, LHVS did not reduce the severity of aGVHD. In fact, LHVS exacerbated a CD4(+)-T cell-dependent model of GVHD similar to chronic GVHD. This suggests that cytokines rather than T cells may mediate much of the damage in the aGVHD model and that therapeutics based on inhibition of antigen presentation for GVHD must be approached with caution.


Assuntos
Apresentação de Antígeno/efeitos dos fármacos , Transplante de Medula Óssea , Linfócitos T CD4-Positivos/efeitos dos fármacos , Catepsinas/antagonistas & inibidores , Dipeptídeos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Sulfonas/administração & dosagem , Animais , Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/imunologia , Catepsinas/imunologia , Inibidores Enzimáticos/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Injeções Intraperitoneais , Complexo Principal de Histocompatibilidade/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor/imunologia , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Transplante Homólogo
19.
Am J Physiol Gastrointest Liver Physiol ; 303(12): G1299-311, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23019194

RESUMO

Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)(2)D(3) to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)(2)D(3) treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)(2)D(3)-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)(2)D(3)-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)(2)D(3) suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.


Assuntos
Calcitriol/efeitos adversos , Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/induzido quimicamente , Infecções por Enterobacteriaceae/imunologia , Hospedeiro Imunocomprometido/imunologia , Mucosa Intestinal/imunologia , Células Th17/imunologia , Animais , Citrobacter rodentium/efeitos dos fármacos , Suscetibilidade a Doenças/induzido quimicamente , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/patologia , Infecções por Enterobacteriaceae/patologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Rheumatology (Oxford) ; 51(3): 552-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22120603

RESUMO

OBJECTIVES: To compare obesity among individuals with PsA, psoriasis (PsO), RA and the general population (n), and identify correlates of obesity among individuals with PsO and PsA. METHODS: We compared the BMI of patients with PsA (n = 644), PsO (n = 448), RA (n = 350) and the general population using age- and sex-adjusted linear and logistic regression analyses. We conducted multivariate analyses limited to PsO and PsA to determine correlates of BMI and obesity. RESULTS: The mean BMI (kilogram per square metre) for individuals with PsA, PsO, RA and the general population were 29.6, 27.9, 27.3 and 26.1, respectively. The proportion with obesity was 37, 29, 27 and 18% for individuals with PsA, PsO, RA and the general population, respectively. The differences in BMI were significant between all categories (P < 0.05) except between PsO and RA. Age- and sex-adjusted linear and logistic regression confirmed that these differences were significant. In multivariate logistic regression analyses adjusted for age, sex, smoking, PsO duration, psoriasis area severity index score, use of DMARDs, glucocorticoids and biologics, the odds of obesity were 61% higher for PsA patients than PsO patients (95% CI 1.10, 2.37). When we additionally adjusted for the physical component summary of the short form-36, the association was attenuated and became insignificant. CONCLUSIONS: Individuals with PsA have a higher mean BMI than those with PsO, RA or the general population. The BMI difference between PsA and PsO correlates with physical health.


Assuntos
Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/fisiopatologia , Índice de Massa Corporal , Obesidade/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Psoríase/fisiopatologia , Fatores de Risco
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