Morphological abnormalities in the lymphocytes of patients with the Wiskott-Aldrich syndrome

Abstract

Lymphocytes from 18 patients with the Wiskott-Aldrich Syndrome (WAS) were examined by scanning electron microscopy (SEM). Most peripheral blood lymphocytes from normal individuals are covered with slender microvillus projections, but a large proportion of lymphocytes from WAS patients were found to be relatively devoid of microvilli. A lymphocyte morphology scoring system was developed to quantify the density of microvilli: Grade 4 classified those lymphocytes with greater than 75% of the surface covered with microvilli with progressive decrements to grade 1, which were those without microvilli. The mean lymphocyte morphology score of eight normal individuals was 3.62 +/- .22. The mean lymphocyte score of WAS patients was substantially lower (2.89 +/- .27, P less than .001). In addition, WAS lymphocytes often were qualitatively abnormal, with short, blunted microvilli. These morphological criteria were used to diagnose WAS from the cord blood lymphocytes of one “at-risk” patient. Thus, WAS is the first primary immunodeficiency in which morphological abnormalities have been identified that can aid in diagnosis.

Regulation of cancer cell motility through actin reorganization

“…Lymphocytes from WAS patients show impaired actin remodeling in response to stimulation as well as a reduction in the number of cell-surface microvilli. (28,29) WASP binds to Cdc42 via its GBD/CRIB (GTPase-binding domain/Cdc42 and Rac interactive binding) domain, and overexpression of WASP induces the formation of actin clusters, suggesting that it has a role in actin polymerization.…”

Efficient antigen presentation of soluble, but not particulate, antigen in the absence of Wiskott–Aldrich syndrome protein

“…19 Also, WASP-de®cient T and B cells possess distorted microvilli. 22,24,25,28 Later complications in WAS include lymphoproliferative disease, especially non-Hodgkin's lymphomas of B-cell origin. 29 A signi®cant number of patients also develop autoimmunity.…”

Early deficit of lymphocytes in Wiskott–Aldrich syndrome: possible role of WASP in human lymphocyte maturation

“…WASP interacts with signalling and adaptor molecules (reviewed in [4]) and plays a critical role in cytoskeletal reorganization by integrating signalling events during T lymphocyte activation. Cytoskeletal defects in patient lymphocyte include a paucity of surface microvilli [5], defective actin polymerization in T cells and T cell lines [6,7], defective internalization of CD3 upon crosslinking of the T-cell receptor (TCR) [8], and a disarrayed F-actin cytoarchitecture documented in B cells [9].…”