Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood

Abstract

Taken together, our findings indicate that DADA2 presents not only with vasculopathy but also with an immunodeficiency of the B cell compartment. Therefore, patients with antibody deficiency should be screened for DADA2. Anti-tumor necrosis factor treatment might improve immunologic features over time and might be considered in patients without vascular manifestations but with elevated inflammation markers. Conservative management has so far proven to be the choice for our less severely affected adolescent and adult DADA2 patients; however, in patients with severe cytopenias and bone marrow failure, hematopoietic stem cell transplantation should be considered.

Human adenosine deaminase 2 deficiency: A multi‐faceted inborn error of immunity

“…Additionally, other disease manifestations such as laboratory abnormalities, individual growth and development, and esophageal varices secondary to portal hypertension improved on therapy . Schepp et al have also reported that suppression of inflammation resulted in restoration of B cell function in patients with mild immunodeficiency. However, the results have been less convincing for DADA2 patients presenting with severe cytopenia and/or immunodeficiency, some of whom failed the treatment and developed life‐threatening infection .…”

“…From the first report on DADA2, features of mild immunodeficiency have been noted, with evidence for mild hypogammaglobulinemia and low IgM serum levels . Subsequently, an immunodeficient phenotype manifesting with recurrent sinopulmonary and herpes virus infections was reported in a subset of patients with DADA2 who were initially diagnosed with common variable immunodeficiency . Of reported patients, at least 25% had hypogammaglobulinemia, 10% had lymphopenia, and 10% had low switched memory B cells.…”

“…Treatment with rituximab can be used for autoantibody induced cytopenia. Supportive treatment with immunoglobulin substitution, antibiotics, and antiviral agents should be started upon indication . As for substitution of the enzyme, infusions of fresh frozen plasma have been attempted; however, the short half‐life of plasma ADA2 make it a less feasible and inefficient approach …”

“…Additionally, other disease manifestations such as laboratory abnormalities, individual growth and development, and esophageal varices secondary to portal hypertension improved on therapy. 3 Schepp et al 78 78 As for substitution of the enzyme, infusions of fresh frozen plasma have been attempted; however, the short halflife of plasma ADA2 make it a less feasible and inefficient approach. 111 Given that myeloid cells are the major source of ADA2, the rationale for HSCT as a definitive cure for DADA2 is clear.…”

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

“…Since the time of the original description, there has been an expansion of the clinical phenotype of cases with DADA2, from cytopaenias and pure red cell aplasia [89], to lymphoproliferative disease [90–92], and combined immune deficiency, as well as common variable immune deficiency (CVID) [93]. Indeed, a cohort study of 181 cases with antibody deficiency diagnosed 11 individuals with mutation and enzyme activity confirmed DADA2 [94]. An interesting finding in this group was that anti-TNF therapy resulted in an improvement in IgM levels in one case, and there was an inverse correlation between c-reactive protein (CRP) and IgG in another.…”