Journal of Clinical Immunology

, Volume 36, Issue 3, pp 179–186 | Cite as

Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency

  • Johanna Schepp
  • Alla Bulashevska
  • Wilma Mannhardt-Laakmann
  • Hongzhi Cao
  • Fang Yang
  • Maximilian Seidl
  • Susan Kelly
  • Michael Hershfield
  • Bodo GrimbacherEmail author
Original Article



Determining the monogenic cause of antibody deficiency and immune dysregulation in a non-consanguineous family with healthy parents, two affected children, and one unaffected child.


Whole Exome Sequencing (WES) was performed in the index family. WES results were confirmed by Sanger Sequencing. Dried plasma spots of the male patient and his mother were analyzed for ADA2 enzymatic activity.


Following data analysis of WES, we found a compound heterozygous mutation in CECR1 (encoding adenosine deaminase 2, ADA2) that segregated in the two affected children. Enzyme activity measurement confirmed a severely diminished ADA2 activity in our patient. The 32 year old index patient was suffering from recurrent respiratory infections and was previously diagnosed with common variable immunodeficiency (CVID), showing no signs of vasculitis. His sister had a systemic lupus erythematosus (SLE)-like phenotype and died at age 17.


Deficiency of ADA2 (DADA2) has been reported to cause vasculopathy and early-onset stroke. Our case suggests that it should also be considered when evaluating patients with antibody deficiencies and immune dysregulation syndromes.


Deficiency of ADA2 primary immunodeficiency common variable immunodeficiency antibody deficiency recurrent infections systemic lupus erythematosus 



The financial support for the conduct of the research came from the German Ministry of Education and Research (BMBF; grants IFB/CCI: 01E01303 and E:med SYSinflame: 01ZX1306F) and the graduate school of the medical faculty Freiburg (MOTIVATE). None of them had any role in study design, the collection, analysis and interpretation of data, the writing of the report, nor in the decision to submit the paper for publication. The authors are responsible for the content of this research.

Our dear collaborator Dr. Wilma Mannhardt-Laakman died in December 2015. We want to thank her for her dedication to caring for this family and so many other children with rheumatological and immunological conditions. We would like to dedicate this publication to her.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Johanna Schepp
    • 1
  • Alla Bulashevska
    • 1
  • Wilma Mannhardt-Laakmann
    • 2
  • Hongzhi Cao
    • 3
  • Fang Yang
    • 3
  • Maximilian Seidl
    • 1
    • 4
  • Susan Kelly
    • 5
  • Michael Hershfield
    • 5
  • Bodo Grimbacher
    • 1
    • 6
    Email author
  1. 1.CCI-Center for Chronic ImmunodeficiencyUniversitätsklinikum FreiburgFreiburgGermany
  2. 2.Zentrum für Kinder- und JugendmedizinUniversitätsmedizin MainzCzernywegGermany
  3. 3.Science and Technology DepartmentBGI-ShenzhenShenzhenChina
  4. 4.Institut für klinische Pathologie, Universitätsklinikum FreiburgFreiburgGermany
  5. 5.Duke Biochemistry, University of DukeDurhamUSA
  6. 6.Institute of Immunology and Transplantation, Royal Free Hospital, University College LondonLondonUK

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