Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome - PubMed (original) (raw)
. 2004 Jul 15;104(2):444-52.
doi: 10.1182/blood-2003-10-3532. Epub 2004 Mar 16.
Daniele Moratto, Silvano Sozzani, Patrizia Cavadini, Karel Otero, Laura Tassone, Luisa Imberti, Silvia Pirovano, Lucia D Notarangelo, Roberta Soresina, Evelina Mazzolari, David L Nelson, Luigi D Notarangelo, Raffaele Badolato
Affiliations
- PMID: 15026312
- DOI: 10.1182/blood-2003-10-3532
Free article
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome
Anna Virginia Gulino et al. Blood. 2004.
Free article
Abstract
The chemokine receptor CXCR4 and its functional ligand, CXCL12, are essential regulators of development and homeostasis of hematopoietic and lymphoid organs. Heterozygous truncating mutations in the CXCR4 intracellular tail cause a rare genetic disease known as WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), whose pathophysiology remains unclear. We report CXCR4 function in 3 patients with WHIM syndrome carrying heterozygous truncating mutations of CXCR4. We show that CXCR4 gene mutations in WHIM patients do not affect cell surface expression of the chemokine receptor and its internalization upon stimulation with CXCL12. Moreover, no significant differences in calcium mobilization in response to CXCL12 are found. However, the chemotactic response of both polymorphonuclear cells and T lymphocytes in response to CXCL12 is increased. Furthermore, immunophenotypic analysis of circulating T and B lymphocytes reveals a decreased number of memory B cells and of naive T cells and an accumulation of effector memory T cells associated with a restricted T-cell repertoire. Based on our results, we suggest that the altered leukocyte response to CXCL12 may account for the pathologic retention of mature polymorphonuclear cells in the bone marrow (myelokathexis) and for an altered lymphocyte trafficking, which may cause the immunophenotyping abnormalities observed in WHIM patients.
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