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Screening assays for primary haemophagocytic lymphohistiocytosis in children presenting with suspected macrophage activation syndrome

Cruikshank, M; Anoop, P; Nikolajeva, O; Rao, A; Rao, K; Gilmour, K; Eleftheriou, D; (2014) Screening assays for primary haemophagocytic lymphohistiocytosis in children presenting with suspected macrophage activation syndrome. Pediatric Rheumatology , 13 , Article 48. 10.1186/s12969-015-0043-7. Green open access

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Abstract

BACKGROUND: Primary haemophagocytic lymphohistiocytosis (HLH) screening assays are increasingly being performed in patients presenting with macrophage activation syndrome (MAS). The objective of this study was to describe their diagnostic and prognostic relevance in children who had presented to paediatric rheumatology and had undergone investigative work up for MAS. METHODS: Data was obtained retrospectively from an existing protein screening assay database and patient records. Assays included: intracellular expression of perforin in CD56+ Natural Killer (NK) cells; CD107a Granule Release Assay (GRA) in response to PHA in NK cells, or anti-CD3 stimulation of CD8 lymphocytes; in males Signal Lymphocyte Activating Molecule Associated Protein (SAP), and X-linked Inhibitor of Apoptosis Protein (XIAP) expression. All assays, requested by paediatric rheumatology, of children who had undergone investigative work up for MAS over a 5-year period (2007-2011) were included. RESULTS: Twenty-one patients (15 female), median age 6.5 years (range 0.6-16) with follow-up of 16 months (range 1-51), were retrospectively identified. At presentation, 3/21 (14 %) fulfilled HLH-2004 diagnostic criteria. At least one screening test result was available for all 21 patients; 7/21 (33 %) had at least one persistent screening test abnormality. Of this group 4/7 (57 %) died or required haematopoietic stem cell transplantation (HSCT), compared to 1/14 (7 %) with no screening test abnormality (p = 0.025). 3/21 (14 %) ultimately had a diagnosis of primary HLH (two confirmed genetically; XIAP, familial HLH type 3, and one confirmed clinically). Of the six patients with abnormal GRA 5/6 had negative routine genetic results. CONCLUSIONS: Screening for primary HLH is warranted for children whose first rheumatological presentation is with MAS, since overall 14 % had an eventual diagnosis of primary HLH. A persistently abnormal GRA in patients presenting with MAS defines a high-risk group with poor outcome (mortality or HSCT), possibly due to as yet unidentified genetic cause.

Type: Article
Title: Screening assays for primary haemophagocytic lymphohistiocytosis in children presenting with suspected macrophage activation syndrome
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12969-015-0043-7
Publisher version: http://dx.doi.org/10.1186/s12969-015-0043-7
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
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 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/1475034
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