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

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.

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.

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.

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.