Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome

Pertovaara, Marja; Raitala, A.; Uusitalo, Hannu; Pukander, J.; Helin, Heikki; Oja, Simo S.; Hurme, Mikko

doi:10.1111/j.1365-2249.2005.02889.x

Cited by 43 publications

(64 citation statements)

References 22 publications

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“…On the other hand, a higher percentage of IDOexpressing APCs was observed supported in pSS than in healthy controls [31]. Increased KYN concentration and KYN/TRP ratio, which reflects the activity of IDO, were also measured in the peripheral blood of pSS patients [32]. In our study, we found that the frequency of IDO-expressing APCs, as well as intracellular IDO content in T cells, was higher in pSS than in controls.…”

Section: Idosupporting

confidence: 54%

The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren’s syndrome and systemic sclerosis

et al. 2016

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B7 costimulatory molecules are present on antigenpresenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a molecule with important immunoregulatory functions. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2 molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28, CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults and 9 SSc and 15 pSS patients using flow cytometry. We also examined the intracellular expression of IDO. The expression of CD28 was lower in both SSc and pSS patients. The frequency of CTLA-4 was increased in pSS. The expression of ICOS, a stimulator of T cell activation, was elevated in pSS, but not in SSc, while that of its corresponding costimulatory molecule, B7-H2, was strongly decreased in SSc compared to controls. The frequency of PD-1 expressing T lymphocytes was decreased in both pSS and SSc. The frequency of IDO-expressing APCs, as well as intracellular IDO content in T cells was higher in pSS than in controls. Our investigation identified a number of differences in B7 costimulation between SSc and pSS patients which may play a role in the distinct pathogenesis and clinical features of these autoimmune disorders.

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Section: Idosupporting

confidence: 54%

The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren’s syndrome and systemic sclerosis

et al. 2016

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“…DC, to express IDO, which can limit T cell responses [24]. Moreover, IDO has been found to be elevated in autoimmune diseases with a female preponderance, for example systemic lupus erythematosus [25] and Sjögren's syndrome [26]. On the other hand, either early atherosclerosis or precociously increased IMT has been found in both these autoimmune diseases [27,28].…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study

Pertovaara

Raitala

Juonala

et al. 2007

Clinical and Experimental Immunology

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133

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SummaryIndoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up-regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, high sensitive C-reactive protein (CRP), body mass index (BMI), waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL-C, BMI, weakly with CRP and inversely with HDL-C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL-C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females.

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“…have been shown to overexpress in a variety of cancers, including lung cancer. However, autoantibodies immunoreactive to these antigens are rarely reported in cancer patients but associated with some inflammatory or metabolic diseases (34,35), implicating that tumor antigen-mediated immunosuppression may occur in tumor malignancy. Consistent with previous studies to detect CML28 (36) and ENO1 (14) autoantibodies in chronic myelogenous leukemia and lung patients, respectively, our data obtained from Western blotting analyses also show that only a small percentage (7.4%) of the cancer patients, including patient CA926, develop high titer of antibodies against ENO1.…”

Section: Discussionmentioning

confidence: 99%

Identification of α-Enolase as an Autoantigen in Lung Cancer: Its Overexpression Is Associated with Clinical Outcomes

Chang

Liu

Hsieh

et al. 2006

Clinical Cancer Research

143

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Purpose: Although existence of humoral immunity has been previously shown in malignant pleural effusions, only a limited number of immunogenic tumor-associated antigens (TAA) have been identified and associated with lung cancer. In this study, we intended to identify moreTAAs in pleural effusion^derived tumor cells. Experimental Design: Using morphologically normal lung tissues as a control lysate inWestern blotting analyses, 54 tumor samples were screened with autologous effusion antibodies. Biochemical purification and mass spectrometric identification of TAAs were done using established effusion tumor cell lines as antigen sources. We identified a p48 antigen as a-enolase (ENO1). Semiquantitative immunohistochemistry was used to evaluate expression status of ENO1 in the tissue samples of 80 patients with non^small cell lung cancer (NSCLC) and then correlated with clinical variables. Results: Using ENO1-specifc antiserum, up-regulation of ENO1expression in effusion tumor cells from 11of 17 patients was clearly observed compared with human normal lung primary epithelial and non-cancer-associated effusion cells. Immunohistochemical studies consistently showed high level of ENO1 expression in all the tumors we have examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed that its expression level in primary tumors was a key factor contributing to overall-and progression-free survivals of patients (P < 0.05). The same result was also obtained in the early stage of NSCLC patients, showing that tumors expressing relatively higher ENO1level were tightly correlated with poorer survival outcomes. Conclusions: Our data strongly support a prognostic role of ENO1in determining tumor malignancy of patients with NSCLC.

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Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome

Cited by 43 publications

References 22 publications

The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren’s syndrome and systemic sclerosis

The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren’s syndrome and systemic sclerosis

Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study

Identification of α-Enolase as an Autoantigen in Lung Cancer: Its Overexpression Is Associated with Clinical Outcomes

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