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Clinical and Diagnostic Laboratory Immunology, December 2005, p. 1437-1441, Vol. 12, No. 12
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.12.1437-1441.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Is Dispensable for Neopterin Production In Vivo

Laboratory of Microbiology-Immunology, Farhat Hached Hospital, Sousse, Tunisia,¹ Laboratory of Human Genetics of Infectious Diseases, University of Paris René Descartes, INSERM U550, Paris, France,² Department of Pediatrics, Farhat Hached Hospital, Sousse, Tunisia,³ Laboratory of Immunology, Institut Pasteur de Tunis, Tunis, Tunisia,⁴ Department of Epidemiology and Biostatistics, Farhat Hached Hospital, Sousse, Tunisia⁵

Received 16 June 2005/ Returned for modification 25 July 2005/ Accepted 2 September 2005

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN- and/or IFN-ß. However, it is unknown if any IFN--independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN- production or function due to severe mutations in molecules involved in IFN-/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN- activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN--, IL-12-, and IL-23-dependent pathway defects.