Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome.

Litzman, Jiří; Jones, Alison; Hann, Ian; Chapel, Helen; Strobel, Sebastian; Morgan, Gabrielle

doi:10.1136/adc.75.5.436

Cited by 82 publications

(51 citation statements)

References 20 publications

(1 reference statement)

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“…These mechanisms could result in the type of episodic thrombocytopenia seen in some WAS patients at presentation [9] and in others after splenectomy [10]. They could also contribute to the chronic thrombocytopenia of WAS patients, given that the latter show increased levels of platelet associated antibodies (seen in 13 of 14 cases in one study [52], and corroborated in several other reports [23,53,54]). Augmented host antigen presentation has also been suggested to underlie the development of autoimmune hemolytic anemia in the context of CD47 deficiency [55].…”

Section: Discussionsupporting

confidence: 62%

Rapid platelet turnover in WASP(−) mice correlates with increased ex vivo phagocytosis of opsonized WASP(−) platelets

Prislovsky

Marathe

Hosni

et al. 2008

Experimental Hematology

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Objective-Our objective was to determine a mechanism for the thrombocytopenia of murine Wiskott-Aldrich syndrome (WAS).Materials and Methods-Consumption rates of WAS protein (WASP)( −) and wild-type (WT) platelets were measured by injection of 5-chloromethylfluorescein diacetate (CMFDA)-labeled platelets into WT or WASP(−) recipients, and by in vivo biotinylation. Platelet and reticulated platelet counts were performed using quantitative flow cytometry. Bone marrow megakaryocyte number and ploidy was assessed by flow cytometry. Phagocytosis of CMFDA-labeled, opsonized platelets was assessed using bone marrow-derived macrophages. Serum antiplatelet antibodies were assayed via their binding to WT platelets.Results-CMFDA-labeled WASP(−) platelets are consumed more rapidly than WT platelets in either WT or WASP(−) recipients. In vivo biotinylation studies corroborate these findings and show a normal consumption rate for WASP(−) reticulated platelets. The number of reticulated platelets is reduced in WASP(−) mice, but a significant number of the mice show an increased proportion of reticulated platelets and more severe thrombocytopenia. Sera from some of the latter group contain antiplatelet antibodies. Compared to WT platelets, WASP(−) platelets opsonized with anti-CD61 or 6A6 antibody are taken up more rapidly by bone marrow-derived macrophages. In vivo consumption rates of WASP(−) platelets are more accelerated by opsonization than are those of WT platelets.Conclusion-Both rapid clearance and impaired production contribute to the thrombocytopenia of murine WAS. Increased susceptibility of opsonized WASP(−) platelets to phagocytosis leads to increased in vivo clearance. This correlates with a higher incidence of individuals with an elevated fraction of reticulated platelets, a more severe thrombocytopenia, and antiplatelet antibodies. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe Wiskott-Aldrich syndrome (WAS) is an X-linked recessive condition of variable penetrance, classically described as a triad of immunodeficiency, eczema, and thrombocytopenia [1,2]. It is caused by mutations that reduce the level of the WAS protein (WASP). WASP is a 54-kDa polypeptide that is expressed primarily, but not exclusively [3,4], in hematopoietic cells. WASP transmits and integrates signals arising at the cell membrane that result in actin polymerization. This can, in turn, have multiple effects, including but not limited to changes in cell shape and motility. While its function in T cells and macrophages has been studied in some detail [5,6], its biological role in platelets is not clear.WAS patients can have severe thrombocytopenia, with platelet counts ranging from 10,000 to 50,000 per uL in one series [7]. In some cases, the thrombocytopenia is the predominant clinical abnormality. These cases, formerly termed X-linked thrombocytopenia, are frequently due to missense mutations in the first four exons of the gene [8], and can show a fluctuating course resembling immune t...

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Section: Discussionsupporting

confidence: 62%

Rapid platelet turnover in WASP(−) mice correlates with increased ex vivo phagocytosis of opsonized WASP(−) platelets

Prislovsky

Marathe

Hosni

et al. 2008

Experimental Hematology

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“…The mainstay of current alternative palliative care is splenectomy and intravenous immune globulin, 5,6 which provides freedom from life-threatening hemorrhage in many, but not all, subjects for months to years. Because most patients with Wiskott-Aldrich syndrome have an inherent deficiency of antibody production to polysaccharide antigens, splenectomy in this setting carries a substantial risk of overwhelming pneumococcal sepsis unless meticulous adherence to prophylactic antibiotics and intravenous immune globulin is maintained.…”

Section: Discussionmentioning

confidence: 99%

“…During this period, only Pneumocystis carinii pneumonia disappeared as a fatal complication. 6 As boys with WiskottAldrich syndrome survive longer, they face increasing risks of life-threatening autoimmune complications and Epstein-Barr virus (EBV)-associated lymphoproliferative disease.…”

mentioning

confidence: 99%

Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program

Filipovich

Stone

Tomany

et al. 2001

Blood

251

170

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Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non-Tcell-depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLAidentical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P ‫؍‬ .0006).

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“…85,89 It is clear that BMT is the treatment of choice and should be done before patients reach school age and have cumulative tissue damage due to infection and autoimmune disease. 86 Common variable immunodeficiency.…”

Section: T-cell Disordersmentioning

confidence: 99%

Autoimmunity in human primary immunodeficiency diseases

Arkwright

Abinun

Cant

2002

Blood

162

106

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Human primary immunodeficiency diseases are experiments of nature characterized by an increased susceptibility to infection. In many cases, they are also associated with troublesome and sometimes life-threatening autoimmune complications. In the past few years, great strides have been made in understanding the molecular basis of primary immunodeficiencies, and this had led to more focused and successful treatment. This review has 3 aims: (1) to highlight the variety of autoimmune phenomena associated with human primary immunodeficiency diseases; (2) to explore how primary immunodeficiencies predispose patients to autoimmune phenomena triggered by opportunistic infections; and (3) to consider the rationale for the current treatment strategies for autoimmune phenomena, specifically in relation to primary immunodeficiency diseases. Reviewing recent advances in our understanding of the small subgroup of patients with defined causes for their autoimmunity may lead to the development of more effective treatment strategies for idiopathic human autoimmune diseases. (Blood. 2002;99:2694-2702

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Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome.

Abstract: ResultsThe median age at diagnosis and the end of the study was 13 (range 1-84) and 82 (range 16-248) months, respectively. Three splenectomised and one non-splenectomised patients died during the total observation period of 436 on 12 May 2018 by guest. Protected by copyright.

Cited by 82 publications

References 20 publications

Rapid platelet turnover in WASP(−) mice correlates with increased ex vivo phagocytosis of opsonized WASP(−) platelets

Rapid platelet turnover in WASP(−) mice correlates with increased ex vivo phagocytosis of opsonized WASP(−) platelets

Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program

Autoimmunity in human primary immunodeficiency diseases

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