Pachman L M, Liotta-Davis M R, Hong D K, Kinsella T R, Mendez E P, Kinder J M, Chen E H
The Children's Memorial Medical Center, Northwestern University Medical School, Chicago, Illinois 60614, USA.
Arthritis Rheum. 2000 Oct;43(10):2368-77. doi: 10.1002/1529-0131(200010)43:10<2368::AID-ANR26>3.0.CO;2-8.
To characterize the association between the TNFalpha-308A allele and 1) duration of active disease, 2) peripheral blood mononuclear cell (PBMC) synthesis of tumor necrosis factor alpha (TNFalpha) in vitro, and 3) pathologic calcifications in patients with juvenile dermatomyositis (DM).
The TNFalpha-308 alleles were determined by polymerase chain reaction in 37 white patients with juvenile DM and in 29 control subjects. Patients were grouped according to duration of immunosuppressive therapy: long (> or =36 months) or short (<36 months). Unstimulated PBMC were examined by enzyme-linked immunosorbent assay for TNFalpha production in vitro. Sixty-five white patients with juvenile DM were examined for pathologic calcifications.
TNFalpha-308A was identified in 18 of 37 patients with juvenile DM, in contrast with 5 of 29 controls (P = 0.009). Sixteen of the 18 patients with juvenile DM who had the TNFalpha-308A allele had a disease course > or =36 months, compared with 6 of 19 patients with TNFalpha-308G (P = 0.001). PBMC from 16 of the 18 juvenile DM patients with TNFalpha-308A synthesized more TNFalpha (median 53 pg/ml) compared with PBMC from 9 of 19 patients with TNFalpha-308G (median 19 pg/ml) (P = 0.007). Nineteen of 22 juvenile DM patients requiring therapy for > or =36 months produced more TNFalpha (median 20.5 pg/ml) in comparison with 6 of 15 juvenile DM patients with a <36-month treatment course (median TNFalpha 0.0 pg/ml) (P = 0.005). Detectable calcifications were present in 3 of 8 children with juvenile DM who had TNFalpha-308AA, compared with 2 of 21 children with TNFalpha-308AG and 1 of 36 children who had TNFalpha-308GG (P = 0.017).
A long course of juvenile DM and the presence of pathologic calcifications were associated with the TNFalpha-308A allele and with the increased production of TNFalpha, which may perpetuate the inflammatory response.
明确肿瘤坏死因子α（TNFα）-308A等位基因与以下三者之间的关联：1）活动期疾病的持续时间；2）外周血单个核细胞（PBMC）在体外合成肿瘤坏死因子α（TNFα）的情况；3）青少年皮肌炎（DM）患者的病理性钙化。
采用聚合酶链反应对37例白人青少年DM患者和29例对照者进行TNFα-308等位基因检测。根据免疫抑制治疗的持续时间对患者进行分组：长疗程（≥36个月）或短疗程（<36个月）。采用酶联免疫吸附测定法检测未刺激的PBMC在体外产生TNFα的情况。对65例白人青少年DM患者进行病理性钙化检查。
37例青少年DM患者中有18例检测到TNFα-308A，而29例对照者中有5例检测到（P = 0.009）。18例携带TNFα-308A等位基因的青少年DM患者中有16例病程≥36个月，而19例携带TNFα-308G的患者中有6例病程≥36个月（P = 0.001）。18例携带TNFα-308A的青少年DM患者中有16例的PBMC合成的TNFα更多（中位数为53 pg/ml），而19例携带TNFα-308G的患者中有9例的PBMC合成的TNFα较少（中位数为19 pg/ml）（P = 0.007）。22例需要治疗≥36个月的青少年DM患者中有19例产生的TNFα更多（中位数为20.5 pg/ml），而15例治疗疗程<36个月的青少年DM患者中有6例产生的TNFα较少（TNFα中位数为0.0 pg/ml）（P = 0.005）。8例携带TNFα-308AA的青少年DM患儿中有3例出现可检测到的钙化，而21例携带TNFα-308AG的患儿中有2例出现钙化，36例携带TNFα-308GG的患儿中有1例出现钙化（P = 0.017）。
青少年DM的长病程和病理性钙化的存在与TNFα-308A等位基因以及TNFα产生增加有关，这可能使炎症反应持续存在。
