Screening for Wiskott-Aldrich syndrome by flow cytometry

Chiang, Samuel C.C.; Vergamini, Sue; Husami, Ammar; Neumeier, Lisa; Quinn, Kathryn; Ellerhorst, Teresa; Sheppard, Linda; Gifford, Carrie; Buchbinder, David; Joshi, Avni Y.; Ifversen, Marianne; Kleiner, Gary; Bussel, James B.; Chandrakasan, Shanmuganathan; Pesek, Robert D.; Pozos, Tamara C.; Rose, Melissa J.; Scurlock, Amy M.; Zhang, Kejian; Bryceson, Yenan T.; Bleesing, Jack J.; Marsh, Rebecca

doi:10.1016/j.jaci.2018.04.017

Cited by 20 publications

(17 citation statements)

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“…WASp expression may be preserved in patients with milder phenotypes with missense variants (46) and mutations involving C terminal end of WAS gene. WASp antibody usually recognizes and binds to epitope in the region between amino acid 146-265 thus resulting in normal WASp expression in some patients (52). Normal WASp levels could also be seen in patients with revertant mutations.…”

Section: Discussionmentioning

confidence: 99%

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

et al. 2021

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BackgroundWiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India.MethodsRequest to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed.ResultsIn this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months).ConclusionsWe report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.

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Section: Discussionmentioning

confidence: 99%

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

et al. 2021

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“…Therefore, we perform analysis of WASp expression as part of our diagnostic work up. WASp quantitation by Western blotting has been superseded in our laboratory by flow cytometry, which has been shown to be a robust and rapid test (Chiang et al , ). It is important to note that protein expression alone cannot absolutely be relied on for diagnosis as missense mutations can sometimes preserve normal levels of functionally impaired WASp.…”

Section: How We Diagnose Was/xltmentioning

confidence: 99%

How I manage patients with Wiskott Aldrich syndrome

et al. 2019

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Summary Wiskott Aldrich syndrome (WAS) is a primary immunodeficiency disease resulting in recurrent infections, eczema and microthrombocytopaenia. In its classical form, significant combined immune deficiency, autoimmune complications and risk of haematological malignancy necessitate early correction with stem cell transplantation or gene therapy. A milder form, X‐linked thrombocytopaenia (XLT), shares similar bleeding risk from thrombocytopaenia but is not associated with other significant clinical features and is generally managed conservatively. Here, we detail our approach to the diagnosis and treatment of classical WAS and XLT.

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“…The neutrophil oxidative burst assay is an excellent assay for the diagnosis of CGD (96). WAS can be accurately diagnosed through direct staining of intracellular WAS protein (97). Multiple excellent reviews exist for PID diagnostics (98, 99).…”

Section: Other Primary Immunodeficienicesmentioning

confidence: 99%

Current Flow Cytometric Assays for the Screening and Diagnosis of Primary HLH

2019

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Advances in flow cytometry have led to greatly improved primary immunodeficiency (PID) diagnostics. This is due to the fact that patient blood cells in suspension do not require further processing for analysis by flow cytometry, and many PIDs lead to alterations in leukocyte numbers, phenotype, and function. A large portion of current PID assays can be classified as “phenotyping” assays, where absolute numbers, frequencies, and markers are investigated using specific antibodies. Inherent drawbacks of antibody technology are the main limitation to this type of testing. On the other hand, “functional” assays measure cellular responses to certain stimuli. While these latter assays are powerful tools that can be used to detect defects in entire pathways and distinguish variants of significance, it requires samples with robust viability and also skilled processing. In this review, we concentrate on hemophagocytic lymphohistiocytosis (HLH), describing the principles and accuracies of flow cytometric assays that have been proven to assist in the screening diagnosis of primary HLH.

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Screening for Wiskott-Aldrich syndrome by flow cytometry

Abstract: are employees of Bean Stalk Snow Co Ltd. The rest of the authors declare that they have no relevant conflicts of interest.

Cited by 20 publications

References 12 publications

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

How I manage patients with Wiskott Aldrich syndrome

Current Flow Cytometric Assays for the Screening and Diagnosis of Primary HLH

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