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Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations.

ABSTRACT: Hypomorphic mutations of the RAG genes in humans are associated with a spectrum of clinical and immunologic presentations that range from T(-) B(-) severe combined immune deficiency (SCID) to Omenn syndrome. In most cases, residual V(D)J recombination activity allows for development of few T-cell clones, which expand in the periphery and infiltrate target organs, resulting in tissue damage. Invariant natural killer T (iNKT) cells play an important immunoregulatory role and have been associated with protection against autoimmunity. We now report on 5 unrelated cases of combined immune deficiency due to hypomorphic RAG mutations, and demonstrate the absence of iNKT cells in all 5 patients. These findings suggest that lack of this important immunoregulatory cell population may contribute to the pathophysiology of Omenn syndrome.

SUBMITTER: Matangkasombut P

PROVIDER: S-EPMC2200812 | biostudies-other | 2008 Jan

REPOSITORIES: biostudies-other

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Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations.

Matangkasombut Ponpan P Pichavant Muriel M Saez Doris E DE Giliani Silvia S Mazzolari Evelina E Finocchi Andrea A Villa Anna A Sobacchi Cristina C Cortes Patricia P Umetsu Dale T DT Notarangelo Luigi D LD

Blood 20070921 1

Hypomorphic mutations of the RAG genes in humans are associated with a spectrum of clinical and immunologic presentations that range from T(-) B(-) severe combined immune deficiency (SCID) to Omenn syndrome. In most cases, residual V(D)J recombination activity allows for development of few T-cell clones, which expand in the periphery and infiltrate target organs, resulting in tissue damage. Invariant natural killer T (iNKT) cells play an important immunoregulatory role and have been associated w ...[more]

PMID: 17890453

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