Reduced purine 5'-nucleotidase activity in lymphocytes of patients with systemic lupus erythematosus: results of a pilot study

Stolk, Jan; Koning, Diana G. M. de; Pennings, A.H.M.; Abreu, Ronney A. De; Putte, L.B.A. van de; Boerbooms, A. M. T.

doi:10.1136/ard.58.2.122

Cited by 11 publications

(7 citation statements)

References 14 publications

(9 reference statements)

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“…Analogously to the 5′NT deficiency that has been associated with azathioprine related bone marrow toxicity we expected, but did not find, low baseline 5′NT activity in this patient group. 25 Also, after six weeks' MTX treatment 5′NT activity had not yet changed from baseline. Apparently, 5′NT decreases at some point between six weeks and the last measurement at study withdrawal.…”

Section: Discussionmentioning

confidence: 96%

Purine enzymes in patients with rheumatoid arthritis treated with methotrexate

Ede

Laan²,

Abreu³

et al. 2002

Annals of the Rheumatic Diseases

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Objectives: To study (a) purine metabolism during treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) and (b) the relation of purine metabolism with efficacy and toxicity of MTX treatment. Methods: One hundred and three patients with active RA who started treatment with MTX were included. The initial MTX dosage was 7.5 mg/week and raised to a maximum of 25 mg weekly if necessary. The purine enzymes 5′-nucleotidase (5′NT), purine-nucleoside-phosphorylase (PNP), hypoxanthine-guanine-phosphoribosyltransferase (HGPRT), and adenosine-deaminase (ADA) were measured before the start, after six weeks, and after 48 weeks or at study withdrawal. The laboratory results were related to measures of efficacy and toxicity of MTX treatment. Results: Baseline values of 5′NT and PNP (16.9 and 206.8 nmol/10 6 mononuclear cells/h, respectively) were similar to those in former studies. Activities of HGPRT and ADA were relatively low at the start (8.7 and 80.3 nmol/10 6 mononuclear cells/h, respectively). After six weeks purine enzyme activities showed no important changes from baseline. After 48 weeks of MTX treatment a decrease of the enzyme activities of ADA (−21.6 nmol/10 6 mononuclear cells/h; 95% CI −28.6 to −14.7), PNP (−78.9 nmol/10 6 mononuclear cells/h; 95% CI −109.0 to −48.7), and HGPRT (−2.0 nmol/10 6 mononuclear cells/h; 95% CI −3.1 to −0.9) was found. No association was shown between the enzyme activities of ADA, PNP, and HGPRT, and the efficacy or toxicity of MTX treatment. In contrast, enzyme activity of 5′NT showed a decrease in the subgroup of patients discontinuing MTX treatment because of hepatotoxicity. Conclusion: MTX treatment in patients with RA leads to a significant decrease of the purine enzyme activities of ADA, PNP, and HGPRT that is not related to the anti-inflammatory efficacy or toxicity of MTX. Hepatotoxicity was related to a decrease in the enzyme activity of 5′NT. These changes may be explained by direct or indirect (via purine de novo and salvage metabolism and the homocysteine pathway) effects of MTX.

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Section: Discussionmentioning

confidence: 96%

Purine enzymes in patients with rheumatoid arthritis treated with methotrexate

Ede

Laan²,

Abreu³

et al. 2002

Annals of the Rheumatic Diseases

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“…Uracil and xanthine are components of pyrimidine or purine metabolism, thus the increased levels of them in urine of SLE patients suggest that nucleotide metabolism in SLE may be disturbed. Similar results were also reported by others (Stolk et al , ). Uridine and hypoxanthine are the major end products of ischemic nucleotide breakdown in the human heart (Burakowski et al , ), and they are further metabolized to uracil and urate, respectively.…”

Section: Resultsmentioning

confidence: 99%

Urinary metabolomic study of systemic lupus erythematosus based on gas chromatography/mass spectrometry

Yan

Huang

Fan

et al. 2016

Biomedical Chromatography

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Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous organ and system manifestations. In this study, urinary metabolic alterations related to SLE were investigated by performing gas chromatography/mass spectrometry (GC/MS) based metabolomics and multivariate statistical analysis. Patients with SLE and healthy controls could be clearly differentiated in view of the metabolic abnormity in urine. Among 70 identified endogenous metabolites, 23 metabolites were dramatically increased in SLE patients, which involved in several key metabolic pathways including energy metabolism, nucleotide metabolism, oxidative stress and gut-microbiome-derived metabolism. This noninvasive and GC/MS-based metabolomic technique is a promising and potent strategy for identifying novel biomarkers and understanding pathogenesis of SLE. Copyright © 2016 John Wiley & Sons, Ltd.

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“…A reduced 5¢NT activity may result in decreased salvage and accumulation of (deoxy) nucleotides and this will disrupt homeostasis of purine metabolism and the processes of DNA and RNA synthesis and repair (17). Subsequently, this may interfere with normal cell function, cause lymphocytotoxicity and a diminished immune function.…”

Section: Discussionmentioning

confidence: 98%

“…5¢NT also represents the major enzyme responsible for the formation of extracellular adenosine from AMP (13) and has a critical role in the functional activation of alloreactive cytotoxic T-lymphocytes (14). Decreased 5¢Nuclotidase activity in human peripheral blood has been reported in a number of immunodeficiency diseases, lymphoproliferative disorders (15), acquired immune deficiency syndrome (16) and in systemic lupus erythematosus (17).…”

Section: Introductionmentioning

confidence: 99%

Adenosine Deaminase and 5′Nucleotidase Activities in Peripheral Blood T Cells of Multiple Sclerosis Patients

et al. 2005

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Multiple sclerosis (MS) is one of the most common causes of neurological disability in young and middle-aged adults and is thought to be mediated by autoreactive T cells. Activities of adenosine deaminase (ADA) and 5'(nucleotidase (5'NT), which are involved in the differentiation and maturation of the lymphoid system, were measured in peripheral blood T cells from 21 MS patients and in 23 age and sex matched healthy controls to determine whether an association existed between these enzyme abnormalities and cellular immune functions. ADA and 5'NT activities were found significantly decreased in MS patients (P < .001 and P < .01 respectively) when compared with controls. Low levels of ADA and 5'NT activities were found irrespective of whether patients had relapsing-remitting or chronic progressive MS. These findings suggest that low levels of these enzyme activities in T cells may be related to the persistent abnormalities in T cell function in the clinical course of MS.

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Reduced purine 5'-nucleotidase activity in lymphocytes of patients with systemic lupus erythematosus: results of a pilot study

Cited by 11 publications

References 14 publications

Purine enzymes in patients with rheumatoid arthritis treated with methotrexate

Purine enzymes in patients with rheumatoid arthritis treated with methotrexate

Urinary metabolomic study of systemic lupus erythematosus based on gas chromatography/mass spectrometry

Adenosine Deaminase and 5′Nucleotidase Activities in Peripheral Blood T Cells of Multiple Sclerosis Patients

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