23.04.2018 - 08:00 Author:
Mari Kaunisto

FIMM Monthly Publication Highlight March 2018: ADA2 deficiency: Clonal lymphoproliferation in a subset of patients

A team led by FIMM Research Director Janna Saarela has shown that a presumptive diagnosis in patients with rare primary immunodeficiency can be very challenging because of the wide clinical spectrum. Exome sequencing has proven to be a powerful tool for identification of new mutations and broadening the phenotypic spectrum of known syndromes. In this article, the group focused on ADA2 deficiency.

Every month we publish a publication highlight that summarises some of the research taking place at FIMM. 

The results of the work were recently published in the Journal of Allergy and Clinical Immunology.

Janna Saarela’s research group utilises whole-exome sequencing to decipher the genetics underlying primary immunodeficiency disorders (PID), a group of rare monogenic disorders leading to defective development and/or function of the immune system. Because of the high clinical and genetic heterogeneity, accurate diagnosis of rare or novel PIDs can often be challenging.

Whole-exome sequencing is a powerful diagnostic tool since it enables both the discovery of previously unknown disease genes and identification of atypical clinical manifestations in known monogenic syndromes, thus broadening their phenotypic spectrum.

In this study, the group focused on the deficiency of adenosine deaminase 2 (DADA2), a recessively inherited disease originally associated with systemic autoinflammation, polyarteritis nodosa –type vasculitis and mild immunodeficiency.

Based on the results, the researchers were able to expand the phenotypic and mutation spectrum of DADA2.

The group exome sequenced 291 unrelated Finnish patients with primary immunodeficiencies and identified four patients with biallelic loss-of-function variants in CECR1, the gene encoding adenosine deaminase 2 (ADA2). One of the identified mutations, p.Arg169Gln, exhibits a significant enrichment in Finns compared with other European populations. This specific mutation was found in 8 patients either as homozygous or in combination with some other CECR1 mutation. The identified patients showed considerable phenotypic heterogeneity, presenting with variable cytopenias, without vascular or hemorrhagic complications.

We complemented the characterization of the classical vasculitic phenotype, and described for the first time atypical symptoms, like, a lymphoproliferative phenotype resembling T-LGL leukemia in a subset of patients.

FIMM PhD student Luca Trotta, the first author of the article


Our findings indicate how challenging a presumptive diagnosis in patients with DADA2 can be because of the wide clinical spectrum. DADA2 should be considered in patients of early-onset lymphoproliferation to   ensure early detection and active treatment of the disease.

Research Director Janna Saarela who led the study


Original publication:

Trotta L, Martelius T, Siitonen T, Hautala T, Hämäläinen S, Juntti H, Taskinen M, Ilander M, Andersson EI, Zavialov A, Kaustio M, Keski-Filppula R, Hershfield M, Mustjoki S, Tapiainen T, Seppänen M, Saarela J. ADA2 deficiency: Clonal lymphoproliferation in a subset of patients. J Allergy Clin Immunol. 2018 Apr;141(4):1534-1537.e8. doi: 10.1016/j.jaci.2018.01.012.



Last updated: 26.04.2018 - 08:19