Understanding the killer-cell immunoglobulin like receptor polymorphism in retinoblastoma. (2nd January 2023)

• Record Type: Journal Article
• Authors: Aggarwal, Ritu; Sharma, Madhulika; Singh, Usha; Poulton, Kay; Bhatia, Tanvi; Mangat, Navdeep; Kakkar, Nandita; Bansal, Deepak
• Is Part Of: Ophthalmic genetics. Volume 44:Number 1(2023)
• Page Start: 1
• Page End: 5
• Publication Date: 2023-01-02
• Subjects: HLA -- Killer cell immunoglobulin like receptor -- retinoblastoma; Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2022.2163404
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Background: The KIR receptors present on the natural killer (NK) cells play a crucial role by exercising cytotoxicity to eliminate tumor cells. Both KIR and class-I HLA molecules exhibit extensive polymorphism. Although RB1 inactivation triggers the initiation of retinoblastoma; however additional immune alterations trigger tumor development. The aim was to explore the KIR/HLA polymorphism and its role in the pathogenesis of retinoblastoma. Methods: Patients with unilateral, non-familial retinoblastoma were enrolled as cases. Healthy individuals matched for ethnicity were enrolled as controls. KIR genotyping was performed by sequence-specific primer assay. The investigated KIR genes included: inhibitory (2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B), activating (2DS1, 2DS2, 2DS3, 2DS4*FUL, 2DS4*DEL, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and pseudogenes (2DP1, 3DP1*FUL, 3DP1*DEL). In addition, HLA ligands were investigated by sequence-specific oligonucleotide assay for HLA-A, B, and C locus. Results: KIR genotyping was performed in 48 cases and 107 controls. The mean age of cases was 2.9 ± 2.2 years (range: 0.25–10). Among the 19 KIR genes, the frequency of KIR2DS4*FUL ( p = 0.0019) and 2DS5 ( p = 0.0095) was increased among cases. HLA ligands were investigated in 25 cases and 50 controls. The frequency of HLA ligands (C1/C2, Bw4, A3/A11) was similar among cases and controls. However, the KIR/HLA combination frequency for KIR3DS1/HLA-Bw4 was decreased in cases ( p = 0.006). Conclusion: It is the pioneer study to report the association of killer cell immunoglobulin-like receptors in retinoblastoma. KIR2DS4*FUL and KIR2DS5 had a susceptible, and KIR3DS1/HLA-BW4 had a protective role in retinoblastoma. The results will aid in exploring the therapeutic potential of NK cell-based therapy for retinoblastoma.