Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency.
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ABSTRACT:
SUBMITTER: Seidel MG
PROVIDER: S-EPMC4429722 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency.
Seidel Markus G MG Hirschmugl Tatjana T Gamez-Diaz Laura L Schwinger Wolfgang W Serwas Nina N Deutschmann Andrea A Gorkiewicz Gregor G Zenz Werner W Windpassinger Christian C Grimbacher Bodo B Urban Christian C Boztug Kaan K
The Journal of allergy and clinical immunology 20141222 5
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Project description:The diagnosis of lipopolysaccharide-responsive beige-like-anchor-protein (LRBA) deficiency currently relies on gene sequencing approaches that do not support a timely diagnosis and clinical management. We developed a rapid and sensitive test for clinical implementation based on the detection of LRBA protein by flow cytometry in peripheral blood cells after stimulation. LRBA protein was assessed in a prospective cohort of 54 healthy donors and 57 patients suspected of LRBA deficiency. Receiver operating characteristics analysis suggested an LRBA:MFI ratio cutoff point of 2.6 to identify LRBA-deficient patients by FACS with 94% sensitivity and 80% specificity and to discriminate them from patients with a similar clinical picture but other disease-causing mutations. This easy flow cytometry-based assay allows a fast screening of patients with suspicion of LRBA deficiency reducing therefore the number of patients requiring LRBA sequencing and accelerating the treatment implementation. Detection of biallelic mutations in LRBA is however required for a definitive diagnosis.
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Project description:BackgroundClinical immunology has traditionally relied on accurate phenotyping of the patient's immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis.ObjectiveWe sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency.MethodsWe performed exome sequencing followed by autozygome filtration.ResultsA truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family.ConclusionThe combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.
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