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

Area of Science:

• Immunology
• Genetics
• Endocrinology

Background:

• Activation-induced cytidine deaminase (AICDA) deficiency is a rare autosomal recessive inborn error of immunity (IEI).
• Understanding the molecular pathogenesis of IEIs like AICDA deficiency is crucial for developing effective treatments.
• The roles of growth factors and oxidative stress in AICDA deficiency are not well understood.

Purpose of the Study:

• To characterize patients with AICDA deficiency.
• To investigate the role of insulin-like growth factor-1 (IGF-1) in AICDA deficiency pathogenesis.
• To assess cellular oxidative stress markers in AICDA deficiency.

Main Methods:

• Patient data was collected from the Kuwait National Primary Immunodeficiency Registry.
• Plasma IGF-1, bromodeoxyuridine (BrdU) incorporation, IGF-1 receptor (IGF-1R) protein, NADPH oxidase activity, and malondialdehyde (MDA) levels were measured.
• ELISA, immunoblot analysis, and colorimetric assays were employed for sample analysis.

Main Results:

• Nine patients with AICDA deficiency were studied, experiencing bacterial infections and some with lymphoproliferation.
• AICDA-deficient patients showed significantly higher plasma IGF-1 and MDA levels compared to controls.
• Increased IGF-1-stimulated DNA synthesis (BrdU incorporation) was observed in peripheral blood mononuclear cells (PBMCs) of AICDA-deficient patients.

Conclusions:

• A novel finding of elevated plasma IGF-1 levels in AICDA-deficient patients was documented.
• Increased IGF-1 may contribute to the pathogenesis of AICDA deficiency.
• These findings could inform future targeted therapies and precision medicine approaches for AICDA deficiency.