IgA肾病和紫癜性肾炎患者单核细胞白细胞介素-1受体拮抗剂的产生能力受其基因多态性的影响(英文)

Gene polymorphism in IL-1 receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis

目的 阐明IL - 1受体拮抗剂 (IL - 1ra)基因多态性对其功能的影响 ,论证IL - 1ra基因型与IgA肾病 (IgAN)及紫癜性肾炎 (HSPN)临床表型之间联系的机理。方法 用PCR方法对IgAN和HSPN病人IL - 1ra基因型进行分析 ,从IL - 1ra不同基因型患者获取外周血单核细胞 ,观察单核细胞经GM -CSF刺激后IL - 1ra、IL - 1α和IL - 1β的产生能力。结果 无论是IgAN ,还是HSPN患者 ,不携带IL - 1ra基因IL1RN * 2等位基因者其单核细胞IL - 1ra的产生能力明显高于携带该等位基因的个体 (IgAN 2 1.5 5± 3.0 8ng/mlvs 13.85± 2 .2 4ng/ml,P <0 .0 0 1;HSPN 2 3.72± 6 .6 8ng/mlvs 12 .6 7± 2 .2 4ng/ml,P <0 .0 1) ,而IL - 1α和IL - 1β的产生能力与是否携带IL1RN * 2等位基因无关。结论 IL - 1ra基因多态性能对其功能产生影响。携带IL1RN * 2等位基因者其体内单核细胞IL - 1ra的产生能力存在缺陷。该结果为临床上根据IL - 1ra基因型有针对地采取干预治疗奠定了基础。

Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.