Polymorphisms of Mannose Binding Lectin gene (MBL2) in Brazilian blood donors (n = 300) (original) (raw)

2009, Journal of Allergy and Clinical Immunology

BACKGROUND: RRP patients show reduced/absent papilloma class I MHC expression, and select class II genes regulate RRP predisposition/severity. HPV-6/11 polarizes innate and adaptive genes toward T H 2-/Treg function. Killer cell immunoglobulin-like receptors (KIR) control the effector function of natural killer (NK) cells and memory CD8 1 T cells that elicit early immune response against viral infections. To determine the role of KIR genes in RRP, we genotyped class I/II MHC and KIR alleles to identify their differential expression in RRP, and effect on infiltrating immunocytes in papillomas. METHODS: Sixty RRP patients/195 healthy controls were typed for 16 known KIR genes by sequence-specific primer-directed PCR. KIR-ligands, HLA-A/B/Cw epitopes were analyzed (direct DNA sequencing). RESULTS: Individual KIRs, genotypes, and class I ligands were similar in patients and controls. However, significant difference between severe (S-RRP) and mild/moderate (MM-RRP) patients were observed when 47 distinct KIR genotypes and distribution were identified in S-RRP, MM-RRP, and controls (p 5 0.024; MC-permuation-x 2). KIR3DS1-/KIR2DS1-S-RRP (78.8%) was more common than MM-RRP (48.5%) (p 5 0.019; Fisher's-exact-test). Patients expressing any RRP-predisposing/severity class II allele (DRB1*0102/DRB1*0301/DQB1*0201) were more frequently KIR3DS1-(p 5 0.006); KIR2DS1-(p 5 0.003); or KIR2DS5-(p 5 0.004), vs. patients expressing 1 of these class II alleles. >77% of S-RRP were KIR3DS1-/KIR2DS1-, and DRB1*0602-(RRP-protective allele) (p 5 0.06). CONCLUSIONS: KIR3DS1/KIR2DS1 absence enhances RRP severity, more so in DQB1*0602patients. Thus, the KIR repertoire may influence papilloma local immunity. Dysfunctional anti-HPV-6/11 NK responses may subvert NK/T-cell HPV clearance. This is the first description of KIR2DS1/KIR3DS1/KIR2DS5 alteration in RRP, and NK/T-cells expressing KIR3DS1/KIR2DS1likely trigger effective anti-HPV immunity that govern HPV-induced disease.