Functional characterization of natural killer cells in type I leukocyte adhesion deficiency.

In this study, we analyzed IL-2-activated polyclonal natural killer (NK) cells derived from 2 patients affected by leukocyte adhesion deficiency type I (LAD1), an immunodeficiency characterized by mutations of the gene coding for CD18, the beta subunit shared by major leukocyte integrins. We show that LAD1 NK cells express normal levels of various triggering NK receptors (and coreceptors) and that mAb-mediated engagement of these receptors results in the enhancement of both NK cytolytic activity and cytokine production. Moreover, these activating NK receptors were capable of recognizing their specific ligands on target cells.

Clinical, immunological and molecular characteristics of 37 Iranian patients with X-linked agammaglobulinemia.

Background: X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency characterized by an early onset of recurrent bacterial infections, a profound deficiency of all immunoglobulin isotypes and a markedly reduced number of peripheral B lymphocytes. Eighty-five percent of the patients with this phenotype have mutations in Bruton's tyrosine kinase (BTK) gene.

Methods: To provide an informative outlook of clinical and immunological manifestations of XLA in Iran, 37 Iranian male patients with an age range of 1-34 years, followed over a period of 25 years, were studied.

T-cell lymphoblastic leukemia/lymphoma in Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare autosomal-recessive disorder characterized by microcephaly, immunodeficiency and predisposition to cancer, mainly B-cell lymphomas. Our 10-years-old female patient with NBS developed T-cell lymphoblastic leukemia/lymphoma (TLBL/ALL). The use of standard chemotherapy in our patient, except for cranial irradiation, led to complete and sustained remission of TLBL/ALL.

Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. X-linked thrombocytopenia (XLT) is an allelic variant of WAS which presents with a milder phenotype, generally limited to thrombocytopenia. WAS and XLT are caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) gene which encodes a 502-amino acid protein, named WASP.

BTK: 22 novel and 25 recurrent mutations in European patients with X-linked agammaglobulinemia.

X linked agammaglobulinemia (XLA) is an immunodeficiency disease caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK), that is involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. XLA is a primary immunodeficiency disorder characterized by lack of mature, circulating B lymphocytes, and recurrent infections. Using Single Strand Conformation Polymorphism (SSCP) followed by direct sequencing we investigated 57 patients with XLA phenotype, with or without a positive family history, from 52 unrelated families enrolled in the Italian XLA Multicenter Clinical Study.

Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency.

beta2 Integrins (CD18) are required for leukocyte migration. In fact, the absence of CD18 results in type-1 leukocyte adhesion deficiency (LAD-1). We analyzed the distribution phenotype and function of dendritic cells (DCs) in three LAD-1 patients with homozygous mutations of CD18.

Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study.

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.