Autoimmunity in Wiskott–Aldrich Syndrome: An Unsolved Enigma

Abstract

Wiskott–Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1–10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was−/− mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

“…1,2 By generating a mouse lacking expression of the WAS protein (WASP) selectively in B lymphocytes (B/WcKO), we and others have revealed a nonredundant B-cell-intrinsic role of WASP in immune homeostasis and prevention of autoimmunity, as well as in marginal zone (MZ) development and regulation of the germinal center (GC) reaction. [3][4][5] Neural WASP (N-WASP, encoded by the Wasl gene) is another member of the WASP family of proteins; it is ubiquitously expressed and shares 50% homology with WASP.…”

Autoimmune Features of Wiskott-Aldrich Syndrome: A Case Report

“…The lung biopsy during this hospitalization, however, was consistent with pauci-immune capillaritis [10,11] and changed the patient's treatment course with rituximab. Treatment for autoimmune disease in WAS may include steroids, cyclophosphamide, azathioprine, IVIG and rituximab [5,12]. Our patient received multiple pulses of high dose methylprednisolone in addition to monthly infusions.…”

“…Capillaritis is generally associated with systemic autoimmune disease, and capillaritis as an isolated entity is relatively rare [7][8][9]. However, autoimmune diseases are common in WAS (22% to 77%) [5,6] and vasculitis is a known complication of WAS occurring in approximately 20% of patients [7]. The types of vasculitis found in WAS include cerebral vasculitis, cardiac vasculitis and Henoch-Schonlein purpura [12,13].…”

High Serum Immunoglobulin E Levels are not Always Due to an Allergy: Hints for Evaluation of the Etiology

“…Periferik yaymada erken yaşlarda başlayan küçük trombositlere eşlik eden trombositopeni vardır. Egzema görülmesi tanıyı destekler (5,6).…”