Autoimmunity in Wiskott–Aldrich Syndrome: Updated Perspectives

Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features

“…Although there was no significant difference among the studied groups, autoimmunity was a prevalent finding in DNMT3B/ZBTB24 (22.2%) and WAS mutations (20%). Similarly, previous studies have reported a high prevalence of autoimmune disorders among WAS patients ( 20 ), but also introduced it as a rare manifestation in mutated DNMT3B/ZBTB24 ( 21 ). Interestingly, these autoimmune manifestations were diagnosed before immunodeficiency in more than two-thirds of the affected patients and even five cases first manifested with autoimmunity.…”

The mosaic of autoimmunity – Finally discussing in person. The 13th international congress on autoimmunity 2022 (AUTO13) Athens

“…Some of the mechanisms responsible for evoking autoimmune responses are closely related to the functioning of the immune system. Rikhi and friends examined the dominancy and phenotype of T cell subsets in 8 patients with immunodeficiency of Wiskott-Aldrich syndrome (WAS) [ 14 ], as patients with WAS were found to be prone to developing autoimmune manifestations [ 15 ]. Among the 8 patients studied, 4 developed an autoimmune disease.…”

Spectrum of Large- and Medium-Vessel Vasculitis in Adults: Neoplastic, Infectious, Drug-Induced, Autoinflammatory, and Primary Immunodeficiency Diseases

“…Thrombocytopenia with small platelets is the signature finding, and susceptibility to bacterial and viral infections, atopy, and autoimmune features are variably present [ 21 , 78 ]. Vasculitides are the second most common autoimmune feature (in 1–29% of patients) [ 22 ]. While SVV, especially IgA vasculitis, is the most frequent vasculitis, necrotizing MVV can occur in various organs and vessels, including the CNS.…”

“…While SVV, especially IgA vasculitis, is the most frequent vasculitis, necrotizing MVV can occur in various organs and vessels, including the CNS. In adults, lymphohistiocytic and/ or granulomatous LVV with propensity to development of aortic aneurysms, is especially noteworthy [22][23][24]26].…”

“…LVV very rare (onset 3 to ~ 50 Y/A) [ 13 , 14 ] ‡ “TAK-like”: aorta (ascending, descending), CCA, subclavian [ 13 , 14 ] (iii) • Further associations with pyoderma gangrenosum, synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO) and IBD [ 13 ] Primary immunodeficiency diseases Common variable immunodeficiency May manifest in childhood or in adulthood at any age; m = f; less common in developing nations; true prevalence of CVID unknown, estimated ~ 0.5–7/10 6 ; any form of vasculitis in ~ 2% of CVID [ 15 ••, 16 , 17 •] ‡ “TAK-like” or TAK: aorta, innominate, CCA, ICA, axillary, subclavian [ 18 – 20 ] + / − “TAK-like” or TAK: renal, mesenteric, celiac, coronary [ 18 – 20 ] • Rule out other causes of hypogammaglobulinemia before diagnosing CVID • Detection of aortic aneurysm in CVID should trigger imaging for LVV • Consider deficiency of adenosin-deaminase-2 in CVID, esp. in patients with MVV • Screen for splenomegaly and lung disease in potential CVID • Limited significance of any serologic test if patient is receiving immunoglobulin replacement therapy Wiskott-Aldrich syndrome Usually diagnosis in early childhood, exceptionally delayed to early adulthood in milder variants; X-linked recessive disorder; prevalence ~ 4/10 6 ; any form of vasculitis in ~ 1 – 29% [ 21 , 22 ] ‡ aorta (frequent aortic aneurysms, often panaortic); + / − aortic arch arteries (“TAK-like”) [ 23 , 24 ] + / − cerebral, kidney, cardiac, liver, bowel, stomach [ 25 , 26 ] • With longer survival of patients with Wiskott-Aldrich, aneurysms secondary to LVV may increasingly become recognized; screening beginning in childhood might be justified • Isolated presentation with thrombocytopenia is commonly called “X-linked thrombocytopenia”, a mild variant of Wiskott-Aldrich • Missing or reduced expression of the “WAS-protein” can be detected rapidly by lymphocyte flow cytometry in peripheral blood [ 21 ] Deficie...…”