IMMUNOSENESCENCE AND ITS IMPACT ON MEDICAL PRACTICE. A NEW LOOK AT AN OLD PROBLEM.

Introdução:O envelhecimento é um processo complexo que influencia todos os sistemas do corpo humano e seu impacto no sistema imune é chamado Imunosenescência. Essa condição é resultado de várias modulações imunológicas causadas por interações entre fatores genéticos e ambientais e é responsável por importantes condições clínicas em indivíduos idosos como alta prevalência de doenças infecciosas e autoimunes, neoplasias e menor eficácia de vacinas. Objetivo: Nesta revisão serão discutidos os problemas clínicos mais comuns na população idosa relacionados a Imunosenescência, e os novos achados da ciência básica relevantes a este tópico. Conclusão: A melhor compreensão da Imunosenescência é importante para prevenção de doenças comuns relacionadas à idade e para a promoção de um envelhecimento saudável.Background: Ageing is a very complex process that modulates all the organ systems of the human body, and its impact on the immune system is called Immunosenescence. This condition is the result of several immune modulations due to genetic and environmental interactions and is responsible for important clinical conditions in elderly subjects, such as a higher incidence of infectious and autoimmune diseases, neoplasias and decreased vaccine efficacy. Objective: In this current review we will discuss the most common clinical problems in the elderly population related to Immunosenescence and new findings in basic science relevant to this topic. Conclusion: A better understanding of Imunosenescence is important to prevention of common age related diseases and for the promotion of healthy ageing

Custos diretos e indiretos do tratamento de pacientes com espondilite anquilosante pelo sistema público de saúde brasileiro

ResumoIntroduçãoOs pacientes com espondilite anquilosante (EA) exigem uma abordagem de equipe com vários profissionais e várias modalidades de tratamento, continuamente; além disso, a doença pode levar à perda da capacidade de trabalho em uma população jovem, de modo que é necessário medir o seu impacto socioeconômico.ObjetivosDescrever o uso de recursos públicos para o tratamento da EA em um hospital terciário após o uso dos fármacos biológicos ter sido aprovado para o tratamento das espondiloartrites pelo Sistema Público de Saúde e estabelecer valores aproximados para os custos diretos e indiretos do tratamento dessa doença no Brasil.Material e métodosForam estimados os custos de tratamento diretos e indiretos de 93 pacientes com EA do ambulatório de espondiloartrite do Hospital de Clínicas da Universidade Federal do Paraná, entre setembro de 2011 e setembro 2012.ResultadosDos pacientes, 70 (75,28%) eram do sexo masculino e 23 (24,72%) do feminino. A idade média foi de 43,95 anos. A duração da doença foi calculada com base na idade do diagnóstico e a média foi de 8,92 anos (desvio padrão: 7,32); 63,44% dos indivíduos usavam fármacos anti‐TNF. Na comparação dos pacientes dos sexos masculino e feminino, a média no Bath Ankylosing Spondylitis Disease Activity Index (Basdai) foi de 4,64 e 5,49, enquanto a média no Bath Ankylosing Spondylitis Functional Index (Basfi) foi de 5,03 e 6,35, respectivamente.ConclusõesOs gastos do sistema público de saúde brasileiro relacionados com a espondilite anquilosante aumentaram nos últimos anos. Uma parte importante desses custos deve‐se à introdução das novas tecnologias de saúde, mais dispendiosas, como no caso da ressonância nuclear magnética e, principalmente, da incorporação da terapia anti‐TNF ao arsenal terapêutico. O custo médio anual direto e indireto do sistema público de saúde brasileiro para tratar de um paciente com espondilite anquilosante, de acordo com os resultados deste estudo, é de US$23.183,56.AbstractIntroductionPatients with Ankylosing Spondylitis (AS) require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio‐economic impact.ObjectivesTo describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil.Material and methods93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation.Results70 patients (75.28$ 23,183.56

Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system

ABSTRACT Introduction: Patients with Ankylosing Spondylitis (AS) require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. Objectives: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. Material and methods: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. Results: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-TNF drugs. Comparing male and female patients the mean BASDAI was 4.64 and 5.49 while the mean BASFI was 5.03 and 6.35 respectively. Conclusions: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-TNF therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56

Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors

Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age >= 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-alpha were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-alpha(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cellsmay differentially impact the development of ANAs and RFs in the elderly. (C) 2015 Elsevier Inc. All rights reserved

Aging disturbs the balance between effector and regulatory CD4+T cells

Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance between effector T (Teff) cells and regulatory T (Treg) cells. Here, we determined if and how aging affects the ratio between Treg and Teff cells. Percentages of both naive Treg (nTreg; CD45RA+CD25(int)FOXP3(low)) and memory Treg (memTreg; CD45RA-CD25(high)FOXP3(high)) cells were determined by flow cytometry in peripheral blood samples of healthy individuals of various ages (20-84 years). Circulating Th1, Th2 and Th17 effector cells were identified by intracellular staining for IFN-γ, IL-4 and IL-17, respectively, upon in vitro stimulation with PMA and calcium ionophore. Whereas proportions of nTreg cells declined with age, memTreg cells increased. Both Th1 and Th2 cells were largely maintained in the circulation of aged humans, whereas Th17 cells were decreased. Similar to memTreg cells, the 3 Teff subsets resided primarily in the memory CD4+ T cell compartment. Overall, Treg/Teff ratios were increased in the memory CD4+ T cell compartment of aged individuals when compared to that of young individuals. Finally, the relative increase of memTreg cells in elderly individuals was associated with poor responses to influenza vaccination. Taken together, our findings imply that aging disturbs the balance between Treg cells and Teff cells

Reduced levels of cytosolic DNA sensor AIM2 are associated with impaired cytokine responses in healthy elderly

Objective: Human aging is associated with remodeling of the immune system. While most studies on immunosenescence have focused on adaptive immunity, the effects of aging on innate immunity are not well understood. Here, we investigated whether aging affects cytokine responses to a wide range of well-defined pattern recognition receptor (PRR) ligands, such as ligands for Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), retinoic-acid-inducible gene-I like receptors (RLRs) and the cytosolic DNA sensor absent in melanoma 2 (AIM2). Method: Blood was collected from 16 young (20-39 years) and 18 elderly (60-84 years) healthy participants. Pro-inflammatory cytokine (TNF-alpha, IL-1 beta, IL-6, and IL-8) production in a whole blood assay (WBA) after stimulation with TLR ligands (Pam3csk4, poly(I:C), LPS, CpG), CLR ligand (beta-glucan), NLR ligand (MDP), RLR ligands (5'ppp-dsDNA and poly(I:C)/lyovec) and the AIM2 ligand (poly(dA:dT) was assessed by ELISA. TLR2 and TLR4 expression by leukocytes and monocytes was determined by flow-cytometry. Expression of AIM2 by peripheral blood mononuclear cells (PBMC) was assessed by qRT-PCR and Western blot. Result: Cytokine responses to Pam3csk4, poly(I: C) and CpG, beta-glucan, MDP, 5'ppp-dsDNA and poly(I: C)/lyovec were comparable between young and old participants. We observed a higher IL-8 response following stimulation of elderly blood samples with the TLR4 ligand LPS, which was associated with higher proportions of TLR4 expressing monocytes. Interestingly, stimulation of whole blood cells with the AIM2 ligand poly(dA: dT) resulted in significantly lower cytokine responses in old participants. Moreover, these lower cytokine responses were associated with lower AIM2 protein expression and activation in PBMC of old participants. Conclusion: Our findings reveal an age-dependent reduction of AIM2 expression and activation which may explain reduced cytokine responses to the cytosolic DNA mimic poly(dA:dT) in healthy elderly individuals. Reduced AIM2-mediated sensing with age may contribute to increased vulnerability to bacterial or viral infections in the elderly. (C) 2016 Elsevier Inc. All rights reserved

Quantifying Distribution of Flow Cytometric TCR-Vβ Usage with Economic Statistics

Measuring changes of the T cell receptor (TCR) repertoire is important to many fields of medicine. Flow cytometry is a popular technique to study the TCR repertoire, as it quickly provides insight into the TCR-Vβ usage among well-defined populations of T cells. However, the interpretation of the flow cytometric data remains difficult, and subtle TCR repertoire changes may go undetected. Here, we introduce a novel means for analyzing the flow cytometric data on TCR-Vβ usage. By applying economic statistics, we calculated the Gini-TCR skewing index from the flow cytometric TCR-Vβ analysis. The Gini-TCR skewing index, which is a direct measure of TCR-Vβ distribution among T cells, allowed us to track subtle changes of the TCR repertoire among distinct populations of T cells. Application of the Gini-TCR skewing index to the flow cytometric TCR-Vβ analysis will greatly help to gain better understanding of the TCR repertoire in health and disease

Monoclonal antibodies.

<p>Overview of fluorochrome-conjugated monoclonal antibodies applied in the study.</p><p>Monoclonal antibodies.</p

Schematic overview showing the relation between T cell receptor (TCR) Vβ diversity, distribution and percentages.

<p>(A) Schematic drawing illustrating broad versus contracted TCR-Vβ diversity. (B) Schematic drawing illustrating distribution and proportional usage of TCR Vβ families when TCR-Vβ diversity is broad or contracted. (C) Schematic drawing illustrating distribution of income among people.</p