Increased IGF‐1 and DNA Synthesis in Patients With Activation‐Induced Cytidine Deaminase Deficiency

Objective To characterize patients with activation‐induced cytidine deaminase (AICDA) deficiency, a rare autosomal recessive inborn error of immunity (IEI), and examine the role of insulin‐like growth factor‐1 (IGF‐1) and cellular oxidative stress in the pathogenesis. Methods Patients data was retrieved from the Kuwait National Primary Immunodeficiency Registry. Plasma IGF‐1 levels were tested by ELISA assay, while bromodeoxyuridine (BrdU) incorporation in peripheral blood mononuclear cells (PBMCs) was used as an index of DNA synthesis. IGF‐1 receptor (IGF‐1R) protein was measured by immunoblot analysis while PBMC NADPH oxidase activity and plasma malondialdehyde (MDA) levels were measured by colorimetric assays. Results Nine patients with AICDA deficiency (6 with c.254G >A and 3 with c.169G >A variants) were included in this study. All patients suffered from bacterial infections, while four had lymphoproliferation. Plasma IGF‐1 and lipid peroxide (MDA) levels were significantly higher in AICDA‐deficient patients when compared with controls ( p ‐values <0.05 and <0.05, respectively). PBMCs isolated from AICDA deficient patients had significantly more IGF‐1‐stimulated BrdU incorporation than controls ( p < 0.01), while IGF‐1R levels were not statistically different. There was no statistical difference in plasma levels of IGF‐1 and DNA synthesis between patients with and without lymphoproliferation. NADPH oxidase activity in PBMC of AICDA patients and controls was not statistically different. Conclusion We documented a novel finding of increased plasma levels of IGF‐1 in AICDA deficient patients. This may help in the future in better understanding the pathogenesis of the disease and possible use of targeted therapy or precision medicine.