Department of Pediatrics, Dokuz Eylül University Medical Faculty, İzmir, Turkey.
Inflammation. 2011 Oct;34(5):379-87. doi: 10.1007/s10753-010-9245-9.
Amyloidosis is the major complication of familial Mediterranean fever (FMF). Toll-like receptors (TLR) are involved in the activation of an innate immune system TLR-2 and TLR-4 recognize lipoteichoic acid and lipopolysaccharides (LPS), respectively. While TLR-2 Arg753Gln polymorphism upregulates, TLR-4 Asp299Gly and Thre399Ile polymorphisms downregulate inflammation. We investigated the effect of these polymorphisms on the development of amyloidosis in FMF patients. We also investigated myeloid cell TLR-2 and TLR-4 expressions in these patients. We studied 26 FMF patients and 13 FMF patients with amyloidosis. TLR-2 Arg753Gln and TLR-4 Asp299Gly and Thr399Ile polymorphisms were analyzed with the polymerase chain reaction-restriction fragment length polymorphism method. Myeloid cell baseline TLR-2 and TLR-4 and LPS-induced TLR-4 expressions were evaluated. The TLR-2 and TLR-4 polymorphism rate was compared with the results of 100 healthy subjects in our previous study. In addition, 13 healthy controls were enrolled for leukocyte TLR-2 and TLR-4 expressions. Serum amyloid A (SAA) levels were measured in these 13 control cases and in FMF patients during attack-free periods. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls in our previous study were 1%, 3%, and 2%, respectively. The frequency of these polymorphisms were not different in FMF patients (with or without amyloidosis) compared to the control group. Likewise, myeloid cell TLR-2 and TLR-4 expressions were not different among the controls and FMF patients. However, LPS-induced TLR-4 expression in granulocytes was more prominent in FMF patients. There was no correlation between TLR-2 and TLR-4 expressions and SAA levels. Neither myeloid cell TLR-2 and TLR-4 expressions nor TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms seem to affect the development of secondary amyloidosis in FMF patients in our study population.
淀粉样变性是家族性地中海热（FMF）的主要并发症。Toll 样受体（TLR）参与固有免疫系统的激活，TLR-2 和 TLR-4 分别识别脂磷壁酸和脂多糖（LPS）。TLR-2 Arg753Gln 多态性上调，而 TLR-4 Asp299Gly 和 Thr399Ile 多态性下调炎症反应。我们研究了这些多态性对 FMF 患者淀粉样变性发展的影响。我们还研究了这些患者的髓样细胞 TLR-2 和 TLR-4 的表达。我们研究了 26 名 FMF 患者和 13 名 FMF 合并淀粉样变性的患者。TLR-2 Arg753Gln 和 TLR-4 Asp299Gly 和 Thr399Ile 多态性通过聚合酶链反应-限制性片段长度多态性方法进行分析。评估了髓样细胞基线 TLR-2 和 TLR-4 以及 LPS 诱导的 TLR-4 表达。将 TLR-2 和 TLR-4 多态性率与我们之前研究中 100 名健康受试者的结果进行比较。此外，还招募了 13 名健康对照者进行白细胞 TLR-2 和 TLR-4 表达。在这 13 例对照病例和 FMF 患者无发作期间测量血清淀粉样蛋白 A（SAA）水平。我们之前研究中健康对照组 TLR-2 Arg753Gln、TLR-4 Asp299Gly 和 Thr399Ile 多态性的频率分别为 1%、3%和 2%。与对照组相比，这些多态性在 FMF 患者（有或没有淀粉样变性）中没有差异。同样，髓样细胞 TLR-2 和 TLR-4 的表达在对照组和 FMF 患者之间也没有差异。然而，FMF 患者的粒细胞中 LPS 诱导的 TLR-4 表达更为明显。TLR-2 和 TLR-4 表达与 SAA 水平之间没有相关性。髓样细胞 TLR-2 和 TLR-4 表达以及 TLR-2 Arg753Gln、TLR-4 Asp299Gly 和 Thr399Ile 多态性似乎都不会影响我们研究人群中 FMF 患者继发性淀粉样变性的发展。
