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Article ; Online: Remodeling of the Immune Response With Aging

Lucas Leite Cunha / Sandro Felix Perazzio / Jamil Azzi / Paolo Cravedi / Leonardo Vidal Riella

Frontiers in Immunology, Vol

Immunosenescence and Its Potential Impact on COVID-19 Immune Response

2020 Volume 11

Abstract: Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in ... ...

Abstract	Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.
Keywords	immunosenescence ; inflammaging ; SARS-CoV-2 ; COVID-19 ; immunopathogenesis ; Immunologic diseases. Allergy ; RC581-607 ; covid19
Subject code	616 ; 610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Body Mass Index and Prognosis of COVID-19 Infection. A Systematic Review

Karina Colombera Peres / Rachel Riera / Ana Luiza Cabrera Martimbianco / Laura Sterian Ward / Lucas Leite Cunha

Frontiers in Endocrinology, Vol

2020 Volume 11

Abstract: A better understanding of the SARS-CoV-2 virus behavior and possible risk factors implicated in poor outcome has become an urgent need. We performed a systematic review in order to investigate a possible association between body weight and prognosis ... ...

Abstract	A better understanding of the SARS-CoV-2 virus behavior and possible risk factors implicated in poor outcome has become an urgent need. We performed a systematic review in order to investigate a possible association between body weight and prognosis among patients diagnosed with COVID-19. We searched in Cochrane Library, EMBASE, MEDLINE, WHO-Global Literature on Coronavirus Disease, OpenGrey, and Medrxiv. We used the ROBINS-I tool or Cross-Sectional/Prevalence Study Quality tool from AHRQ, to evaluate the methodological quality of included studies. Nine studies (two prospective cohorts, four retrospective cohorts and three cross-sectional) were included and assessed the relationship between obesity and COVID-19 prognosis. Risk of bias of the included studies ranged from moderate to critical. Clinical and methodological heterogeneity among them precluded meta-analyses. Most of the included studies showed some degree of association to: (a) higher BMI and worse clinical presentation and (b) obesity and need of hospitalization. The results were inconsistent about the impact of obesity on mortality. Based on limited methodological quality studies, obesity seems to predict poor clinical evolution in patients with COVID-19. Further studies with appropriate prospective design are needed to reduce the uncertainty on this evidence.
Keywords	obesity ; body mass index ; SARS-CoV-2 ; COVID-19 ; risk factor ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665 ; covid19
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Table_1_Body Mass Index and Prognosis of COVID-19 Infection. A Systematic Review.DOCX

Karina Colombera Peres / Rachel Riera / Ana Luiza Cabrera Martimbianco / Laura Sterian Ward / Lucas Leite Cunha

2020

Abstract	A better understanding of the SARS-CoV-2 virus behavior and possible risk factors implicated in poor outcome has become an urgent need. We performed a systematic review in order to investigate a possible association between body weight and prognosis among patients diagnosed with COVID-19. We searched in Cochrane Library, EMBASE, MEDLINE, WHO-Global Literature on Coronavirus Disease, OpenGrey, and Medrxiv. We used the ROBINS-I tool or Cross-Sectional/Prevalence Study Quality tool from AHRQ, to evaluate the methodological quality of included studies. Nine studies (two prospective cohorts, four retrospective cohorts and three cross-sectional) were included and assessed the relationship between obesity and COVID-19 prognosis. Risk of bias of the included studies ranged from moderate to critical. Clinical and methodological heterogeneity among them precluded meta-analyses. Most of the included studies showed some degree of association to: (a) higher BMI and worse clinical presentation and (b) obesity and need of hospitalization. The results were inconsistent about the impact of obesity on mortality. Based on limited methodological quality studies, obesity seems to predict poor clinical evolution in patients with COVID-19. Further studies with appropriate prospective design are needed to reduce the uncertainty on this evidence.
Keywords	Endocrinology ; Reproduction ; Cell Metabolism ; obesity ; body mass index ; SARS-CoV-2 ; COVID-19 ; risk factor ; covid19
Subject code	610
Publishing date	2020-08-14T12:21:53Z
Publishing country	uk
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

Guilherme Augusto Barcelos Domingues / Marina Malta Letro Kizys / Carolina Castro Porto Silva Janovsky / Rui Monteiro de Barros Maciel / Magnus Régios Dias-da-Silva / João Roberto Maciel Martins / Cleber Pinto Camacho / Lucas Leite Cunha

Archives of Endocrinology and Metabolism, Vol 66, Iss 1, Pp 112-

2022 Volume 117

Abstract: SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous ... ...

Abstract	SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.
Keywords	Medicine ; R ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Subject code	610 ; 616
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Brazilian Society of Endocrinology and Metabolism
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Homer's odyssey and Brazilian universities

Lucas Leite Cunha / Laura Sterian Ward

Clinics, Vol 67, Iss 11, Pp 1235-

2012 Volume 1235

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2012-11-01T00:00:00Z
Publisher	Faculdade de Medicina / USP
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RORγt may Influence the Microenvironment of Thyroid Cancer Predicting Favorable Prognosis

Lucas Leite Cunha / Elaine Cristina Morari / Suely Nonogaki / Natassia Elena Bufalo / Ligia Vera Montalli da Assumpção / Fernando Augusto Soares / José Vassallo / Laura Sterian Ward

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract We aimed to investigate the role of RORγt (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). ...

Abstract	Abstract We aimed to investigate the role of RORγt (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). Immunohistochemical expression of RORγt was compared to other immune markers previously investigated by our group, clinical and pathological information. All patients presented cytoplasmic expression of RORγt in thyroid tumor cells. Seven (12.5%) patients presented no nuclear expression of RORγt. Positivity was few (up to 10%) in 14 patients; 10 to 50% in 5 patients (8.9%); and more than 50% in 30 patients (53.6%). Nuclear RORγt positivity was associated with absence of distant metastasis at diagnosis (p = 0.013) and the need of less cumulative doses of radioactive iodine (p = 0.039). Patients whose tumors were positive for nuclear RORγt presented higher 10-years relapse-free survival rate than those patients who were negative for RORγt (p = 0.023). We classified the patients according to the clustering of immunological immunohistochemical markers. We were able to distinguish a subset (A) of 38 patients who presented high expression of nuclear RORγt and tended to be scarce in proinflammatory immune markers. Other 16 patients integrated a second subset (B) whose tumor microenvironment accumulated proinflammatory markers and presented low expression of nuclear nuclear RORγt. Distant metastasis at diagnosis were more frequent among patients from cluster B than from cluster A (p = 0.008). Our results reinforce that the expression of RORγt together with other immune markers might help predict the prognosis of patients with thyroid cancer and help individualize clinical management.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

Lucas Leite Cunha / Elaine Cristina Morari / Suely Nonogaki / Fernando Augusto Soares / José Vassallo / Laura Sterian Ward

Clinics, Vol 67, Iss 5, Pp 483-

2012 Volume 488

Abstract: OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in ...

Abstract	OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.
Keywords	FoxP3 ; Regulatory T Lymphocytes ; Differentiated Thyroid Carcinoma ; Medicine (General) ; R5-920
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Elsevier España
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

Lucas Leite Cunha / Alfio Jose Tincani / Ligia Vera Montalli da Assumpção / Fernando Augusto Soares / José Vassallo / Laura Sterian Ward

Clinics, Vol 66, Iss 7, Pp 1203-

2011 Volume 1208

Abstract: OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent ... ...

Abstract	OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.
Keywords	Tumor immunity ; Interleukin-10 ; Interleukin-18 ; Chronic lymphocytic thyroiditis ; Immunogenetics ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Elsevier España
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

Marjory Alana Marcello / Elaine Cristina Morari / Lucas Leite Cunha / Aline Carolina De Nadai Silva / Dirce Maria Carraro / André Lopes Carvalho / Fernando Augusto Soares / José Vassallo / Laura Sterian Ward

Clinical and Developmental Immunology, Vol

2013 Volume 2013

Abstract: Background. Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers ... ...

Abstract	Background. Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC). Methods. ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also, TP53 was sequenced in 78 out of 164 patients with papillary thyroid carcinoma. Results. P53 expression was observed more frequently in malignant than in benign lesions (P<0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller (P=0.0015), unique tumors (P=0.0286), with thyroiditis (P=0.0486) and without metastasis at diagnosis (P=0.0201). TAM was more frequent in P53 negative tumors (P=0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC (P<0.001). Conclusions. We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.
Keywords	Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Immunologic diseases. Allergy ; RC581-607
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer

Marjory Alana Marcello / Antonio Ramos Calixto / Jacqueline Fatima Martins de Almeida / Mariana Bonjiorno Martins / Lucas Leite Cunha / Camila Ayume Amano Cavalari / Elba C. S. Etchebehere / Ligia Vera Montalli da Assumpção / Bruno Geloneze / Andre Lopes Carvalho / Laura Sterian Ward

International Journal of Endocrinology, Vol

2015 Volume 2015

Keywords	Diseases of the endocrine glands. Clinical endocrinology ; RC648-665 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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