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1.
Expert Rev Clin Immunol ; 16(5): 527-538, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32478627

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects almost every organ system and it is treated with immunomodulation and immunosuppression. SLE patients have an intrinsically dysfunctional immune system which is exacerbated by disease activity and leaves them vulnerable to infection. Treatment with immunosuppression increases susceptibility to infection, while hydroxychloroquine use decreases this risk. Infectious diseases are a leading cause of hospitalization and death. AREAS COVERED: This narrative review provides an overview of recent epidemiology and predictors of infections in SLE, delineates the risk of infection by therapeutic agent, and provides suggestions for risk mitigation. Articles were selected from Pubmed searches conducted between September 2019 and January 2020. EXPERT OPINION: Despite the large burden of infection, effective and safe preventative care such as universal hydroxychloroquine use and vaccination are underutilized. Future efforts should be directed to quality improvement, glucocorticoid reduction, and validation of risk indices that identify patients at the highest risk of infection.

2.
Arthritis Care Res (Hoboken) ; 72(12): 1800-1808, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31609532

RESUMO

OBJECTIVE: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. METHODS: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. RESULTS: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6-18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. CONCLUSION: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.

3.
Arthritis Care Res (Hoboken) ; 70(9): 1294-1302, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29193883

RESUMO

OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling. METHODS: Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. RESULTS: A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day). CONCLUSION: Patients with estimated GFR <30 ml/minute incurred 10-year costs 15-fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies.


Assuntos
Nefrite Lúpica/economia , Adulto , Estudos de Coortes , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Adulto Jovem
4.
Curr Opin Rheumatol ; 29(5): 480-485, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28520683

RESUMO

PURPOSE OF REVIEW: The present review addresses recent literature investigating the socioeconomic consequences of systemic lupus erythematosus (SLE). We highlight the latest updates on health disparities affecting the SLE population, the direct and indirect economic costs of the disease, and less quantifiable costs such as reduced health-related quality of life (HRQoL). RECENT FINDINGS: Health disparities continue to exist among socially disadvantaged populations, including African Americans, Hispanics, and patients with decreased educational attainment and in poverty. Direct and indirect costs are substantial. Recent work provides updated cost estimates for patients with SLE outside of North America, including those in developing countries. Previous research has largely focused on costs of the general SLE population and those with renal manifestations or active SLE, whereas recent research addresses special populations such as hospitalized and pregnant patients and glucocorticoid users. Patients with SLE and their caregivers experience a substantially reduced HRQoL. SUMMARY: SLE is a costly disease that disproportionately affects disadvantaged populations. Future economic studies should measure not only direct costs, but also incorporate indirect costs and the HRQoL of both patients with SLE and their caregivers. All these components are essential to provide a comprehensive assessment of the socioeconomic consequences of SLE and an appreciation of the potential impact of novel therapies.


Assuntos
Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Nível de Saúde , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/economia , Lúpus Eritematoso Sistêmico/epidemiologia , Morbidade/tendências , América do Norte/epidemiologia , Índice de Gravidade de Doença , Fatores Socioeconômicos
5.
Dev Comp Immunol ; 41(3): 377-88, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23624185

RESUMO

Birds have a smaller repertoire of immune genes than mammals. In our efforts to study antiviral responses to influenza in avian hosts, we have noted key genes that appear to be missing. As a result, we speculate that birds have impaired detection of viruses and intracellular pathogens. Birds are missing TLR8, a detector for single-stranded RNA. Chickens also lack RIG-I, the intracellular detector for single-stranded viral RNA. Riplet, an activator for RIG-I, is also missing in chickens. IRF3, the nuclear activator of interferon-beta in the RIG-I pathway is missing in birds. Downstream of interferon (IFN) signaling, some of the antiviral effectors are missing, including ISG15, and ISG54 and ISG56 (IFITs). Birds have only three antibody isotypes and IgD is missing. Ducks, but not chickens, make an unusual truncated IgY antibody that is missing the Fc fragment. Chickens have an expanded family of LILR leukocyte receptor genes, called CHIR genes, with hundreds of members, including several that encode IgY Fc receptors. Intriguingly, LILR homologues appear to be missing in ducks, including these IgY Fc receptors. The truncated IgY in ducks, and the duplicated IgY receptor genes in chickens may both have resulted from selective pressure by a pathogen on IgY FcR interactions. Birds have a minimal MHC, and the TAP transport and presentation of peptides on MHC class I is constrained, limiting function. Perhaps removing some constraint, ducks appear to lack tapasin, a chaperone involved in loading peptides on MHC class I. Finally, the absence of lymphotoxin-alpha and beta may account for the observed lack of lymph nodes in birds. As illustrated by these examples, the picture that emerges is some impairment of immune response to viruses in birds, either a cause or consequence of the host-pathogen arms race and long evolutionary relationship of birds and RNA viruses.


Assuntos
Proteínas Aviárias/deficiência , Galinhas/imunologia , Imunidade Inata , Imunoglobulina D/deficiência , Fatores Reguladores de Interferon/deficiência , Receptores Imunológicos/deficiência , Ubiquitina-Proteína Ligases/deficiência , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/imunologia , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Evolução Biológica , Galinhas/microbiologia , Galinhas/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Imunoglobulina D/genética , Imunoglobulina D/imunologia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Mamíferos/imunologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia
6.
Mol Immunol ; 54(1): 89-97, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23220072

RESUMO

Ducks can survive infection with highly pathogenic avian influenza viruses that are lethal to chickens. We showed that the influenza detector, RIG-I can initiate antiviral responses in ducks, but this gene is absent in chickens. We can reconstitute this pathway by transfecting chicken DF-1 embryonic fibroblast cells with duck RIG-I, which augments their antiviral response to influenza and decreases viral titer. However, the genes downstream of duck RIG-I that mediate this antiviral response to influenza are not known. Using microarrays, we compared the transcriptional profile of chicken embryonic fibroblasts transfected with duck RIG-I or empty vector, and infected with low or highly pathogenic avian influenza viruses. Transfected duck RIG-I expressed in chicken cells was associated with the marked induction of many antiviral innate immune genes upon infection with both viruses. We used real-time PCR to confirm upregulation of a subset of these antiviral genes including MX1, PKR, IFIT5, OASL, IFNB, and downregulation of the influenza matrix gene. These results provide some insight into the genes induced by duck RIG-I upon influenza infection, and provide evidence that duck RIG-I can function to elicit an interferon-driven, antiviral response against influenza in chicken embryonic fibroblasts.


Assuntos
Aves/genética , Aves/imunologia , RNA Helicases DEAD-box/fisiologia , Imunidade Inata/genética , Influenza Aviária/genética , Influenza Aviária/imunologia , Animais , Células Cultivadas , Embrião de Galinha , Galinhas/genética , Galinhas/imunologia , Análise por Conglomerados , Patos/genética , Patos/imunologia , Perfilação da Expressão Gênica , Imunidade Inata/imunologia , Análise em Microsséries
8.
Mol Immunol ; 48(15-16): 1950-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21704378

RESUMO

Ducks are the natural host and reservoir of influenza viruses. We are interested in their immune responses to these viruses, to understand host-pathogen interactions and to develop effective agricultural vaccines. We identified duck homologues of the chemokines CCL19 and CCL21 and cloned their cognate receptor, CCR7. Conservation of key features, and expression in lymphoid tissues suggests that these chemokines are the direct orthologues of their mammalian counterparts. Mammalian CCL19 and CCL21 are responsible for the homing of dendritic cells and naïve lymphocytes to secondary lymphoid tissues. The contribution of local tertiary lymphoid tissues may be important during influenza infection in ducks. Consistent with leukocyte recruitment, CCL19 and CCL21 transcripts are abundant in lung tissues at 1 day post-infection with highly pathogenic avian influenza A/Vietnam/1203/04 (H5N1) (VN1203). In contrast, expression in lung or intestine tissues infected with low pathogenic A/mallard/BC/500/05 (H5N2) (BC500) is not significant. Recruitment and aggregation of leukocytes is visible in the vicinity of major airways 3 days after infection with VN1203. Chemokine gene expression may serve as a useful marker to evaluate duck immune responses to natural infections and vaccine strains.


Assuntos
Quimiocina CCL19/imunologia , Quimiocina CCL21/imunologia , Patos/imunologia , Influenza Aviária/imunologia , Receptores CCR7/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Quimiocina CCL19/genética , Quimiocina CCL21/genética , Patos/genética , Virus da Influenza A Subtipo H5N1 , Tecido Linfoide/imunologia , Dados de Sequência Molecular , Filogenia , Receptores CCR7/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
Proc Natl Acad Sci U S A ; 107(13): 5913-8, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20308570

RESUMO

Ducks and wild waterfowl perpetuate all strains of influenza viruses in nature. In their natural host, influenza viruses typically cause asymptomatic infection and little pathology. Ducks are often resistant to influenza viruses capable of killing chickens. Here, we show that the influenza virus sensor, RIG-I, is present in ducks and plays a role in clearing an influenza infection. We show evidence suggesting that RIG-I may be absent in chickens, providing a plausible explanation for their increased susceptibility to influenza viruses compared with ducks. RIG-I detects RNA ligands derived from uncapped viral transcripts and initiates the IFN response. In this study, we show that the chicken embryonic fibroblast cell line, DF-1, cannot respond to a RIG-I ligand. However, transfection of duck RIG-I into DF-1 cells rescues the detection of ligand and induces IFN-beta promoter activity. Additionally, DF-1 cells expressing duck RIG-I have an augmented IFN response resulting in decreased influenza replication after challenge with either low or highly pathogenic avian influenza virus. Implicating RIG-I in the antiviral response to an infection in vivo, we found that RIG-I expression is induced 200 fold, early in an innate immune response in ducks challenged with the H5N1 virus A/Vietnam/1203/04. Finding this natural disease resistance gene in ducks opens the possibility of increasing influenza resistance through creation of a transgenic chicken.


Assuntos
Proteínas Aviárias/genética , Proteínas Aviárias/imunologia , Patos/genética , Patos/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Galinhas/genética , Galinhas/imunologia , Primers do DNA/genética , Virus da Influenza A Subtipo H5N1/genética , Influenza Aviária/genética , Influenza Aviária/imunologia , Influenza Aviária/virologia , Interferon beta/genética , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Interferência de RNA , RNA Viral/genética , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Transfecção
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