Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency

Rich, Kenneth; Arnold, W; Palella, Thomas D.; Fox, Irving H.

doi:10.1016/0002-9343(79)90100-1

Cited by 49 publications

(18 citation statements)

References 15 publications

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“…Firstly, several disturbances of purine metabolism have been associated with immune disorders. [3][4][5][6][7][8][9][10][11] In RA, in which a dysregulation of the immune system also may play a part, changes in purine enzymes have been reported. [11][12][13] Secondly, the outcome of treatment with azathioprine (efficacy as well as toxicity) in patients with RA has been associated with low activities of purine enzymes.…”

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confidence: 99%

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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confidence: 99%

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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“…Family one includes 2 brothers, ages 9 and 1 1 years, with recurrent infections, lymphopenia, and abnormal cellular immunity with intact humoral immunity (6,7). In family two there is a 5-year-old boy with similar abnormalities (8).…”

Section: Methodsmentioning

confidence: 99%

Purine Nucleoside Phosphorylase Deficiency

Wortmann

Andres

Kaminska

et al. 1979

Arthritis & Rheumatism

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The biochemical features of two families with purine nucleoside phosphorylase deficiency are compared. Laboratory studies and an evaluation of kinetic and physical properties of erythrocyte purine nucleoside phosphorylase give evidence that a) the degree of abnormality in uric acid and nucleoside concentrations in plasma and urine reflect the severity of the enzymatic deficiency and b) structural alterations of the mutant enzymes result from structural gene mutations and demonstrate genetic heterogeneity in the disease purine nucleoside phosphorylase deficiency.Purine nucleotide degradation is an intricately regulated enzymatic sequence. The relevance of these enzyme reactions to clinical disorders of immune function was first noted when adenosine deaminase deficiency was found associated with combined B-and T-cell dysfunction (1). The observations that purine nucleoside phosphorylase deficiency occurs with cellular immune dysfunction (2-8) and ecto-5'-nucleotidase Submitted for publication November 2, 1978; accepted January 9, 1979. deficiency occurs with agammaglobulinemia (9) further emphasized this relationship.Purine nucleoside phosphorylase is an integral part of the nucleotide degradation pathway. A deficiency of this enzyme blocks this reaction sequence and results in an immune disorder (2-8). The enzyme deficiency and the concomitant clinical syndrome may result from structural gene mutations (10,ll). We have examined the clinical features and biochemical properties of the enzyme from 3 patients in two families with purine nucleoside phosphorylase deficiency. The data indicate that the laboratory changes observed in the patients reflect the degree of enzyme deficiency and that altered properties of the deficient enzymes provide evidence for a structural gene alteration and genetic heterogeneity in the disease purine nucleoside phosphorylase deficiency.

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“…Adenosine deaminase (ADA)' deficiency results in severe combined immunodeficiency disease with impairment of T-and B-lymphocyte function (1). Purine nucleoside phosphorylase (PNP) deficiency has been associated with T-lymphocyte dysfunction in nine patients (2)(3)(4)(5)(6)(7)(8)(9). The mechanism(s) whereby these enzyme deficiency states affect lymphocyte development and/or function has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%