p53 Autoantibodies in Patients with Autoimmune Diseases: A Quantitative Approach

Kuhn, Hella-Monika; Kromminga, Arno; Flammann, H.T.; Frey, Markus; Layer, Peter; Arndt, R.

doi:10.3109/08916939908994068

Cited by 25 publications

(15 citation statements)

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“…Thus, the immunogen that actually drives the autoimmune reaction to DNA is probably not DNA itself. Recent reports have shown the existence of anti-p53 antibodies in SLE patients [28]. The p53 molecule features a DNA-binding domain that allows it to recognize damaged DNA.…”

Section: Discussionmentioning

confidence: 99%

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

et al. 2003

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Introduction: Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective: To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-α, TNF-α), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods: p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-α were studied by enzyme-linked immunonosorbent assay. Results: SLE patients had higher levels of p53 protein (0.16 ± 0.33 ng/dl) than controls (0.014 ± 0.02 ng/dl; p = 0.006). Patients with active SLE had higher levels of p53 (0.31 ± 0.48 ng/dl) than those with inactive disease (0.08 ± 0.17 ng/dl; p = 0.003) who in turn had higher levels than controls (0.01 ± 0.02 ng/dl; p = 0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R = +0.24/ p = 0.04), anti-DNA antibodies (R = +0.23/p = 0.048) and IL-10 levels (R = +0.4/p = 0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-α levels. Conclusions: The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells.

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Section: Discussionmentioning

confidence: 99%

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

et al. 2003

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“…Alguns grupos vêm estudando a associação entre doenças autoimunes e anticorpos anti-p53 (19,20). O p53 é um "gene sentinela", cuja expressão aumenta quando ocorrem danos estruturais do DNA, com o objetivo de propiciar um ambiente celular favorável ao reparo ou determinar apoptose caso o reparo não seja possível.…”

Section: Discussionunclassified

“…O p53 é um "gene sentinela", cuja expressão aumenta quando ocorrem danos estruturais do DNA, com o objetivo de propiciar um ambiente celular favorável ao reparo ou determinar apoptose caso o reparo não seja possível. Este é o gene mais comumente mutado em neoplasias humanas e a presença de anticorpos contra o seu produto coloca o indivíduo em risco aumentado de doenças neoplásicas (20).…”

Section: Discussionunclassified

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Avaliação da incidência e do comportamento do câncer de tireóide em pacientes com doença de graves submetidos a tireoidectomia

Peixoto

Taboada

Wagman

et al. 2003

Arq Bras Endocrinol Metab

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Arq Bras Endocrinol Metab vol 47 nº 5 Outubro 2003 RESUMOA fim de avaliar a incidência, comportamento, evolução clínica e determinação de possíveis fatores preditivos da associação entre carcinoma de tireóide (CT) e Doença de Graves (DG), analisamos os prontuários de todos os pacientes submetidos à tireoidectomia para tratamento definitivo de DG em 2 hospitais universitários, entre 01/79 e 11/02. Dos 341 pacientes identificados, o exame histológico das peças cirúrgi-cas revelou CT em 7 (2,1%). A idade dos pacientes do grupo sem CT variou de 13 a 79 anos (mediana: 34) e naqueles com CT variou de 19 a 50 anos (mediana: 29), sem diferença significativa entre os grupos. Havia 293 mulheres (87,7%) e 41 homens (12,3%) no grupo sem CT e 5 mulheres (71,5%) e 2 homens (28,5%) no grupo com CT. O tipo histológico presente em todos os casos foi carcinoma papilífero de tireóide (CPT), sendo um caso de CPT multicêntrico sem acometimento extra-tireoidiano, 2 casos de variante folicular com 8 e 25mm de diâmetro, sem invasão capsular, um caso de CPT clássico com 15mm de diâmetro e nos 3 restantes, microcarcinoma (<10mm de diâmetro). O acompanhamento dos pacientes variou de 6 a 16 anos, e nenhum apresentou recorrência local da doença, ou metástases à distância. Nesta casuística, a incidência de CT em pacientes operados por DG foi concordante com dados da literatura. Não observamos agressividade maior do que a usual, talvez pela grande freqüência de carcinomas ocultos. To evaluate the incidence, behavior, clinical outcome and identify possible predictive factors of the association between thyroid cancer (TC) and Graves' disease (GD), we reviewed the records from all patients submitted to thyroidectomy for treatment of GD between 01/79 and 11/02 from 2 university hospitals. Histology of the excised specimens identified TC in 7 of the 341 patients (2.1%). In the group with TC, age varied from 19 to 50 years (median: 29) and in those without TC, from 13 to 79 years (median: 34), which were not significantly different. There were 293 women (87.7%) and 41 men (12.3%) in the non-TC group and 5 women (71.5%) and 2 men (28.5%) in the TC group. By histology, all 7 cases of TC were papillary thyroid carcinoma (PTC): one with a multicentric PTC without extra-thyroidal involvement, two with the follicular variant of PTC (with 8 and 25mm diameter) but no capsular involvement, one with classic PTC (with 15mm diameter), and the remaining 3 with microcarcinomas (<10mm). Patients were followed from 6 to 16 years and none had local recurrence or distant metastasis. Our data showed an incidence of TC in patients submitted to surgery for GD concordant with those previously reported. Tumors were not more aggressive than usual, probably because of the high frequency of occult microcarcinomas.

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“…For example, there is greater invasion of inflammatory and fibroblast cells into IR damaged tissues in p53-null compared to WT mice [25]. Several autoimmune disorders characterized by increased or deregulated inflammation including rheumatoid arthritis, ulcerative colitis and lupus (systemic lupus erythematosus-SLE) exhibit elevated p53 protein or defective p53 functions [26][27][28][29][30][31], tying p53 dysfunction to autoimmunity. Furthermore, increased p53 protein expression within inflamed tissues has been associated with the appearance of somatic dominant-negative p53 mutations [29,32,33].…”

Section: Inflammation and P53: Maintaining Homeostasismentioning

confidence: 99%

Modulation of immune responses by the tumor suppressor p53

Lowe¹,

Shatz²,

Resnick³

et al. 2013

Biodiscovery

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The commonly held view of the tumor suppressor p53 as a regulator of cell proliferation, apoptosis and senescence has expanded greatly in recent years to cover many biological processes as well as external and internal stress responses. Since the discovery over 30 years ago of p53 as a cellular protein that co-precipitates with the large T antigen of Simian Virus SV40, there has been an intertwining of p53 activities with immunerelated processes, especially as relates to cancer. A variety of interactions between the p53 and the immune stress systems are currently being addressed that suggest opportunities to utilize p53 in modulating immunological activities. Here, we discuss those interactions along with implications for human disease.

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p53 Autoantibodies in Patients with Autoimmune Diseases: A Quantitative Approach

Cited by 25 publications

References 3 publications

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

Relationship of p53 with other Oncogenes, Cytokines and Systemic Lupus Erythematosus Activity

Avaliação da incidência e do comportamento do câncer de tireóide em pacientes com doença de graves submetidos a tireoidectomia

Modulation of immune responses by the tumor suppressor p53

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