Verification of X-linked lymphoproliferative syndrome type 1 and 2 using a flow cytometry method

D. Е. Pershin; Першин Д. Е.; V. А. Vedmedskaya; Ведмедская В. А.; M. S. Fadeeva; Фадеева М. С.; I. S. Vladimirov; Владимиров И. С.; E. A. Kulakovskaya; Кулаковская Е. А.; A. A. Roppelt; Роппельт А. А.; A. M. Kieva; Киева А. М.; E. V. Raykina; Райкина Е. В.; Yu. A. Rodina; Родина Ю. А.; M. A. Maschan; Масчан М. А.; A. Yu. Shcherbina; Щербина А. Ю.

doi:10.24287/1726-1708-2020-19-4-108-118

Verification of X-linked lymphoproliferative syndrome type 1 and 2 using a flow cytometry method

Authors: Pershin D.Е.¹, Vedmedskaya V.А.¹, Fadeeva M.S.¹, Vladimirov I.S.¹, Kulakovskaya E.A.¹, Roppelt A.A.¹, Kieva A.M.¹, Raykina E.V.¹, Rodina Y.A.¹, Maschan M.A.¹, Shcherbina A.Y.¹
Affiliations:
1. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Ministry of Healthcare of Russian Federation
Issue: Vol 19, No 4 (2020)
Pages: 108-118
Section: ORIGINAL ARTICLES
Submitted: 21.12.2020
Accepted: 21.12.2020
Published: 08.07.2025
URL: https://hemoncim.com/jour/article/view/426
DOI: https://doi.org/10.24287/1726-1708-2020-19-4-108-118
ID: 426

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Abstract

Х-linked lymphoproliferative syndrome (XLP) is a life-threatening primary immunodeficiency, characterized by hemophagocytic lymphohistiocytosis, lymphoproliferation and hypogammaglobulinemia. The most frequent forms of XLP – XLP1 and XLP2 – are caused by mutations of the SH2D1A and BIRС4/XIAP genes, coding for SAP and XIAP proteins, respectively. Early diagnosis is important as it allows to prevent severe complications by introducing specific therapy and proceed to hematopoietic stem cell transplantation. Here we describe validation of precise and fast flow cytometry-based method of XLP1 and XLP2 laboratory diagnostics. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 89 patients from 2 months to 18 years of age seen at our Center from July 2016 to February 2020 with symptoms suspicious of XLP were included in the study. Decrease of SAP intracellular expression was found in 9 patients, and XIAP – in 10 patients. In all of them XLP diagnosis was confirmed by detection of SH2D1A or XIAP mutations, respectively. Female mutations carries from the families of these patients demonstrated abnormal expression of respective proteins. Analysis of the data allowed to calculated the optimized cut-off numbers for the SAP and XIAP expression, which was 50% and 80% in T lymphocytes (respectively) and 45% и 75% in NK lymphocytes (respectively). Specificity and sensitivity of the method was 100% for both proteins. Therefore the method of assessment of SAP and XIAP intracellular expression via flow cytometry allows fast and precise diagnostics of XLP1 and XLP2.

Keywords

primary immunodeficiency, flow cytometry, X-linked lymphoproliferative syndrome, hemophagocytic lymphohistiocytosis, SH2D1A gene, SAP, XIAP gene, iNKT, SAP protein, XIAP protein

About the authors

D. Е. Pershin

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Ministry of Healthcare of Russian Federation

Author for correspondence.
Email: dimprsh@icloud.com
ORCID iD: 0000-0002-6148-7209

Dmitry Е. Pershin, Junior Researcher, Doctor of Medical Laboratory, Laboratory of Hematopoietic stem cell transplantation and Immunotherapy

1 Samory Mashela St., Moscow 117997

Russian Federation

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