Elevated IgM levels as a marker for a unique phenotype in patients with Ataxia telangiectasia

Alexander Krauthammer,Raz Somech,Lior Goldberg,Michalle Soudack,Ifat Sarouk,Itai M Pessach,Avishay Lahad,Batia Weiss

doi:10.1186/s12887-018-1156-1

Alexander Krauthammer, Raz Somech + Show 6 more

Open Access

https://doi.org/10.1186/s12887-018-1156-1

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Abstract

BackgroundAtaxia telangiectasia (AT) is a rare, multi-systemic, genetic disorder. Mutations in the ATM gene cause dysfunction in cell-cycle, apoptosis and V (D) J recombination leading to neurodegeneration, cellular, humoral immunodeficiencies and predisposition to malignancies. Previous studies have suggested that a sub-group of AT patients with elevated IgM levels have a distinct and more severe phenotype. In the current study we aimed to better characterize this group of patients.MethodsWe performed a retrospective review of 46 patient records, followed from January 1986 to January 2015 at the Israeli National AT Center. Demographic, clinical, radiological, laboratory data was reviewed and compared between AT patients with elevated IgM levels (EIgM) and patients with normal IgM levels (NIgM).Results15/46(32.6%) patients had significantly elevated IgM levels. This group had a unique phenotype characterized mainly by increased risk of infection and early mortality. Colonization of lower respiratory tract with Mycobacterium gordonae and Pseudomonas aeruginosa as well as viral skin infections were more frequent in EIgM patients. Patients with NIgM had a significantly longer survival as compared to patients with EIgM but had an increased incidence of fatty liver or cirrhosis. T-cell recombination excision circles and kappa-deleting element recombination circle levels were significantly lower in the EIgM group, suggesting an abnormal class switching in this group.ConclusionsEIgM in AT patients are indicative of a more severe phenotype that probably results from a specific immune dysfunction. EIgM in AT should be considered a unique AT phenotype that may require different management.

Highlights

Ataxia telangiectasia (AT) is a rare, multi-systemic, genetic disorder
Infections and immune function We retrospectively reviewed all the available laboratory data of the immune system from patient’s charts, including complete blood counts, immunoglobulin levels and distribution, T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) levels as well as T and B cell subpopulations
Out of 46 patients with available immunoglobulin M (IgM) values, 15/46(33%) had elevated IgM levels (EIgM) with average serum IgM levels of 356 ± 200 mg/dl that were statistically higher than the average IgM levels seen in the normal IgM levels (NIgM) group (129.2 ± 56.5 mg/dl, p < 0.001)

Summary

Introduction

Mutations in the ATM gene cause dysfunction in cell-cycle, apoptosis and V (D) J recombination leading to neurodegeneration, cellular, humoral immunodeficiencies and predisposition to malignancies. Previous studies have suggested that a sub-group of AT patients with elevated IgM levels have a distinct and more severe phenotype. Mutations in the ATM gene causes dysfunction in cell cycle, apoptosis, DNA repair and V (D) J recombination [1,2,3]. Patients that have no ATM kinase activity are highly affected, while those with residual kinase activity usually present less severe neurologic disabilities and milder immune deficiency [5,6,7]. The humoral immunodeficiency in AT includes IgG2 and IgG4 deficiencies, low or absent IgA and IgE and abnormal humoral response to vaccination [2]. Krauthammer et al BMC Pediatrics (2018) 18:185 liver abnormalities and insulin resistant diabetes are a part of the AT phenotype [12,13,14]

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