Anifrolumab, a potential treatment for ADA2 deficiency

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Adenosine deaminase 2 deficiency (DADA2) is an inborn error of immunity causing systemic vasculitis, immune deficiency, and autoimmunity.
• DADA2 diagnosis can be challenging due to overlapping symptoms with other autoimmune diseases like systemic lupus erythematosus (SLE).

Purpose of the Study:

• To report a challenging case of DADA2 initially diagnosed as SLE.
• To investigate the therapeutic potential of anifrolumab in DADA2.
• To explore the relationship between DADA2 and type I interferonopathies.

Main Methods:

• Case report of a 26-year-old female with atypical SLE presentation.
• Genetic analysis revealing a homozygous CECR1/ADA2 variant.
• Treatment with anifrolumab and assessment of clinical response and inflammatory markers (IFN-I score, TNFα, IL-6).

Main Results:

• The patient, initially diagnosed with SLE, was re-diagnosed with DADA2 due to hypogammaglobulinaemia and B-cell lymphopenia.
• Anifrolumab treatment led to rapid clinical remission and reduced corticosteroid dependence.
• Anifrolumab therapy was associated with a lower type I interferon (IFN-I) score and sustained low TNFα and IL-6 levels compared to anti-TNFα therapy.

Conclusions:

• DADA2 diagnosis requires careful evaluation of atypical presentations, especially in SLE patients with hypogammaglobulinaemia.
• Anifrolumab shows promise as a novel therapeutic option for DADA2, potentially targeting the type I interferon pathway.
• This case highlights DADA2 as a condition on the spectrum of type I interferonopathies.