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The WHIM Syndrome

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Humoral Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

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Abstract

The WHIM syndrome is a rare immunodeficiency characterized by Warts, Hypogammaglobulinemia, recurrent respiratory bacterial Infections, and Myelokathexis. Early studies identified that neutrophils in WHIM patients are retained in the bone marrow; severe peripheral neutropenia and lymphocytopenia were also observed. Infections of the upper respiratory tracts and lesions due to human papillomavirus (HPV) are common. Association with tetralogy of Fallot and Waldenström macroglobulinemia was described. The WHIM syndrome is mostly caused by heterozygous mutations on chromosome 2q21 that truncate the C-terminal tail of the chemokine receptor CXCR4, the cognate receptor to chemokine CXCL12. The CXCR4-CXCL12 interaction plays a key role in the recruitment of hematopoietic progenitors into the bone marrow and in the regulation of lymphocyte trafficking within secondary lymphoid organs. Current recommendations for WHIM syndrome include vaccinations and antibiotics to prevent infections, as well as usage of G-CSF and as an immune cell-mobilizing agent to combat myelokathexis. Intravenous immunoglobulin (IVIG) injections can be used to treat hypogammaglobulinemia.

Given the ability of AMD3100 to inhibit CXCR4 signaling, it has been suggested as a therapy for myelokathexis in WHIM syndrome.

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Author information

Authors and Affiliations

  1. Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano, Italy

    Giuliana Roselli & Marinos Kallikourdis

  2. Department of Biomedical Sciences, Humanitas University, Rozzano, Italy

    Marinos Kallikourdis

  3. Department of Biomedical Sciences, University of Padova, Padova, Italy

    Antonella Viola

  4. Pediatric Research Institute “Citta della Speranza”, Padova, Italy

    Antonella Viola

Authors
  1. Giuliana Roselli
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  2. Marinos Kallikourdis
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  3. Antonella Viola
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Correspondence to Antonella Viola .

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Editors and Affiliations

  1. Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy

    Mario Milco D'Elios

  2. University Medical Centre Freiburg, Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Freiburg, Germany

    Marta Rizzi

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Roselli, G., Kallikourdis, M., Viola, A. (2019). The WHIM Syndrome. In: D'Elios, M., Rizzi, M. (eds) Humoral Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-91785-6_14

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  • DOI: https://doi.org/10.1007/978-3-319-91785-6_14

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