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Clinical and Diagnostic Laboratory Immunology, January 2001, p. 133-137, Vol. 8, No. 1
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.1.133-137.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A Point Mutation in a Domain of Gamma Interferon Receptor 1 Provokes Severe Immunodeficiency

Luis M. Allende,¹ Alberto López-Goyanes,¹ Estela Paz-Artal,¹ Alfredo Corell,¹ M. Angel García-Pérez,¹ Pilar Varela,¹ Atilio Scarpellini,² Sagrario Negreira,² Elia Palenque,³ and Antonio Arnaiz-Villena^1,*

Department of Immunology,¹ Department of Pediatrics (Infectious Diseases Unit),² and Department of Microbiology,³ Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, 28041 Madrid, Spain

Received 24 July 2000/Returned for modification 26 September 2000/Accepted 13 October 2000

Gamma interferon (IFN-) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN- receptor ligand-binding chain (IFN-R1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-R1 ligand-binding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN- (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN- receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.

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^* Corresponding author. Mailing address: Department of Immunology, Hospital Universitario 12 de Octubre, Universidad Complutense, Carretera de Andalucía, 28041 Madrid, Spain. Phone: 34-91-3908315. Fax: 34-91-3908399. E-mail: aarnaiz{at}eucmax.sim.ucm.es.

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Clinical and Diagnostic Laboratory Immunology, January 2001, p. 133-137, Vol. 8, No. 1
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.1.133-137.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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