Urinary Neopterin in Pulmonary Sarcoidosis: Relationship to Clinical and Biologic Assessment of the Disease

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Abstract
Neopterin is a metabolite of guanosine-triphospate, released in vitro by macrophages under the control of gamma-interferon and described as a marker of T cell activation in vivo. We have compared the urinary neopterin/creatinine ratio (.mu.mol/mol) in patients with pulmonary sarcoidosis (n=66), interstitial lung diseases other than sarcoidosis (nonsarcoid ILD, n = 35), and 45 nromal control subjects. For this sarcoid population as a whole, urinary neopterin was higher (496 .+-. 52 .mu.mol/mol [mean .+-. SEM]) than in control subjects (126 .+-. 5 .mu.mol/mol) (p < 0.001). In patients with nonsarcoid ILD, urinary neopterin was frequently higher in granulomatous and/or lymphoproliferative diseases (hypersensitivity pneumonitis, tuberculosis, primitive Sjogren''s syndrome, and malignant lymphomas) (781 .+-. 193 .mu.mol/mol, n = 10) but remained normal in other types of nonsarcoid ILD ([163 .+-. 14 .mu.mol/mol, n = 25]: histiocytosis X, idiopathic pulmonary fibrosis, lung collagen-vascular diseases, diffuse neoplasms, pneumoconiosis; p < 0.001 compared with sarcoidosis). We have also evaluated the relationship between urinary neopterin and the clinical or biologic markers currently used to assess sarcoidosis: alveolar lymphocytosis in lavage fluid (ALY), 67-gallium scan semiquantitative index (67Ga), or serum angiotensin-converting enzyme (SACE). Sarcoid patients with the highest urinary neopterin were those in whom mean values of these markers were the highest (p < 0.05, all comparisons). Patients with positive markers (i.e., either clinical expression of sarcoidosis-ALY > 30%-67Ga > 20-SACE > 60 U/ml) had significantly higher urinary neopterin levels than did other sarcoid patients (p < 0.05, all comparisons). Moreover, urinary neopterin values correlated significantly with the number of positive markers found in each of the 42 patients in whom all measurements were made and exhibited the best sensitivity in predicting abnormalities of those markers. Preliminary data concerning the evolution of 22 sarcoid patients over a period of 11 .+-. 1 months suggest that urinary neopterin levels could reflect the progression of sarcoidosis at least when the disease improves. These data suggest that measurement of urinary neopterin, at which is simple to perform, noninvasive, and inexpensive, can take place in diagnostic strategies for dealing with interstitial lung diseases and can be helpful for the management of patients with pulmonary sarcoidosis.