PB2024 A RARE CAUSE OF NEUTROPHIL FUNCTION DISORDER: THE MUTATION IN IKBKB GENE

Abstract

Background: Some patients with severe combined immunodeficiency may have normal T-cell counts with a severe immune-cell activation defect in complex signaling that regulates transcriptional programs. The nuclear factor κB (NF-κB) pathway plays a role in inflammatory and immune responses, cell adhesion, and protection against apoptosis. NF-κB pathway activation requires degradation of the NF-κB inhibitor (IκB) proteins initiated by their phosphorylation by the IκB kinase (IKK) complex consisting of two active kinases, IKKα and IKKβ. The IκB kinase (IKK) complex links these transcription factors to immune receptors. Several primary immunodeficiencies in humans are caused by an impaired IKK–IκB axis. The mutation in IKBKB is characterized by viral,fungal,bacterial infections that leads to the life-threatening consequences. The patients have agammaglobulinemia/hypogammaglobulinemia and normal lymphocyte count. Aims: Here, we describe an infant with a severe combined immunodeficiency with homozygous IKBKB mutation because of rarity. Methods: The 40 day-old girl applied to the hospital with perianal and periumbilical abcesses. She was the second child from the first generation consanguineous parents. There was history of sibling death with unknown ethiology at age of 5 th months. Results: The immunological investigations revealed that she had WBC:27190 mm3/L, absolute neutrophil count:6150 mm3/L, absolute lymphocyte count:10740 mm3/L, IgG:287 mg/dl, IgA:6.2 mg/dl, IgM:17.4 mg/dl, IgE:17.7 IU/ml, CD4:55.6%, CD8:29.7%, CD3: 83.8%, CD16+56:6.3%, CD19:7.1%, CD45:99.9%, CD11/CD18:98%. The homozygous missense c.965_967delTCC;p.IIe322_His323delins Asn variant in IKKβ gene was identified. Although she was administrated intensive antibiotic and immunoglobulin therapy, she died at 5 th month of age because of septic shock. Summary/Conclusion: As a result, the case report is first for presentation of SCID with normal lymphocyte count, agammaglobulinemia and homozygous missense mutation in IKBKB gene in the medical literatüre.