Department of Hematology-Hemostasis, University Hospital of Tours, France.
Thromb Res. 2012 Apr;129(4):465-9. doi: 10.1016/j.thromres.2011.09.033. Epub 2012 Jan 10.
Heparin-induced thrombocytopenia (HIT) results from an atypical immune response with synthesis of IgG antibodies (Abs) to platelet factor 4/heparin complexes (PF4/H), and probably involves both B and T cells. We investigated whether 3 single nucleotide polymorphisms (SNPs), rs1800896 (-1082G/A), rs1800871 (-819C/T) and rs1800872 (-592C/A) and the polymorphic CA repeat microsatellites IL10R [5325CA(11_15)] and IL10G [8134CA(14_29)] are associated with the synthesis of Abs to PF4/heparin and HIT.
Eighty-two patients with definite HIT and two control groups were studied. The first control group (Ab(neg)) consisted of 85 patients without Abs to PF4/heparin after cardiopulmonary bypass (CPB). The second control group (Ab(pos)) consisted of 84 patients who had developed significant levels of PF4-specific antibodies after CPB, but without HIT.
Allele frequencies of the 3 SNPs were similar in HIT patients and controls. Fourteen alleles in IL10G (G16 to G29) and 3 alleles in IL10R (R13 to R15) were defined. The short G20 allele of IL10G was more frequent in Ab(neg) patients (8.2%) than in Ab(pos) (2.9%) and HIT patients (3%). It thereby appeared to protect against developing Abs to PF4/heparin (OR 0.29; 95% CI [0.12-0.70], p=0.006). Combined haplotypes cH1/cH8 comprising the short G20 + R13 alleles were less frequent in HIT (OR 0.33; 95% CI [0.11-0.97], p=0.036), and levels of Abs to PF4 in Ab(pos) patients were lower in cH1/cH8 subjects (p=0.019).
These results suggest that IL10 promoter microsatellite polymorphisms might influence the immune response against PF4/heparin and the risk of HIT.
肝素诱导的血小板减少症（HIT）是由针对血小板因子 4/肝素复合物（PF4/H）的异常免疫反应引起的，可能涉及 B 和 T 细胞。我们研究了三个单核苷酸多态性（SNP），rs1800896（-1082G/A）、rs1800871（-819C/T）和 rs1800872（-592C/A）以及多态性 CA 重复微卫星 IL10R [5325CA(11_15)]和 IL10G [8134CA(14_29)]是否与 PF4/肝素的 Abs 合成和 HIT 相关。
研究了 82 例明确的 HIT 患者和两个对照组。第一个对照组（Ab(neg)）由 85 例体外循环（CPB）后无 PF4/肝素 Abs 的患者组成。第二个对照组（Ab(pos)）由 84 例 CPB 后出现明显 PF4 特异性抗体但无 HIT 的患者组成。
HIT 患者和对照组的 SNP 等位基因频率相似。在 IL10G 中定义了 14 个等位基因（G16 至 G29）和 3 个等位基因（R13 至 R15）。IL10G 的短 G20 等位基因在 Ab(neg)患者（8.2%）中比 Ab(pos)（2.9%）和 HIT 患者（3%）更为常见。因此，它似乎可以防止 PF4/肝素的 Abs 形成（OR 0.29；95%CI [0.12-0.70]，p=0.006）。包含短 G20+R13 等位基因的组合单倍型 cH1/cH8 在 HIT 中较少见（OR 0.33；95%CI [0.11-0.97]，p=0.036），并且 Ab(pos)患者的 PF4 Abs 水平在 cH1/cH8 患者中较低（p=0.019）。
这些结果表明，IL10 启动子微卫星多态性可能影响针对 PF4/肝素的免疫反应和 HIT 的风险。
