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Key diagnostic markers for Autoimmune Lymphoproliferative Syndrome with molecular genetic diagnosis

Molnár, E; Radwan, N; Kovács, G; Andrikovics, H; Henriquez, F; Zarafov, A; Hayman, M; ... Gilmour, K; + view all (2020) Key diagnostic markers for Autoimmune Lymphoproliferative Syndrome with molecular genetic diagnosis. Blood , 136 (17) pp. 1933-1945. 10.1182/blood.2020005486. Green open access

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Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a rare immunodeficiency caused by mutations in genes affecting the extrinsic apoptotic pathway (FAS, FASL, CASP10). This study evaluated the clinical manifestations, laboratory findings and molecular genetic results of 215 patients referred as possible ALPS. Double negative T-cell (DNT) percentage and in vitro apoptosis functional tests were evaluated by FACS; interleukin 10 and 18 (IL-10, -18) and soluble FAS ligand (sFASL) were measured by ELISA. Genetic analysis was performed by next generation sequencing. Clinical background data were collected from patients' records. Patients were categorised into definite, suspected and unlikely ALPS, and laboratory parameters were compared among these groups. From 215 patients, 38 met the criteria for definite ALPS and 17 for suspected ALPS. The definite and suspected ALPS patient population showed higher DNT than unlikely ALPS and had higher rates of lymphoproliferation. Definite ALPS patients had a significantly more abnormal in vitro apoptosis function with lower annexin than patients with suspected ALPS (P=0.002) and patients not meeting the ALPS criteria (P<0.001). The combination of elevated DNT and an abnormal in vitro apoptosis functional test was the most useful to identify all types of ALPS patients; the combination of abnormal in vitro apoptosis functional test and elevated sFASL was a predictive marker for ALPS-FAS group identification. Lymphoproliferation, apoptosis functional test and DNT are the most sensitive markers; elevated IL-10 and IL-18 are additional indicators for ALPS. The combination of elevated sFASL and an abnormal apoptosis function was the most valuable prognosticator for patients with FAS mutations.

Type: Article
Title: Key diagnostic markers for Autoimmune Lymphoproliferative Syndrome with molecular genetic diagnosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood.2020005486
Publisher version: https://doi.org/10.1182/blood.2020005486
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: autoimmune lymphoproliferative syndrome, genetics, molecular, interleukin-10, tumor necrosis factor ligand superfamily member 6, annexins, genetic analysis, high-throughput nucleotide sequencing, immunologic deficiency syndromes, interleukin-18, laboratory test finding
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10105390
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