Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.
Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.
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DOI：
10.1084/jem.20021769
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发表时间：
2003-02-17
期刊：
影响因子：
--
通讯作者：
Casanova JL
中科院分区：
文献类型：
--
作者：
Fieschi C;Dupuis S;Catherinot E;Feinberg J;Bustamante J;Breiman A;Altare F;Baretto R;Le Deist F;Kayal S;Koch H;Richter D;Brezina M;Aksu G;Wood P;Al-Jumaah S;Raspall M;Da Silva Duarte AJ;Tuerlinckx D;Virelizier JL;Fischer A;Enright A;Bernhöft J;Cleary AM;Vermylen C;Rodriguez-Gallego C;Davies G;Blütters-Sawatzki R;Siegrist CA;Ehlayel MS;Novelli V;Haas WH;Levy J;Freihorst J;Al-Hajjar S;Nadal D;De Moraes Vasconcelos D;Jeppsson O;Kutukculer N;Frecerova K;Caragol I;Lammas D;Kumararatne DS;Abel L;Casanova JL
由于报道的患者数量较少，白细胞介素 12 受体 β1 链 (IL-12Rβ1) 缺陷的临床表型和人 IL-12 在宿主防御中的功能仍然很大程度上未知。我们现在报告了来自 17 个国家的 41 名完全 IL-12Rβ1 缺乏症患者。在 34 名患者中观察到的唯一机会性感染是儿童期发病，由弱毒力沙门氏菌或分枝杆菌（卡介苗 -BCG- 和环境分枝杆菌）引起。三名患者患有临床结核病，其中一名患者还患有沙门氏菌病。与沙门氏菌病不同，分枝杆菌感染不会复发。卡介苗接种和卡介苗疾病均能有效对抗随后的环境分枝杆菌病，但对沙门氏菌病无效。除先证者外，12 名受影响的兄弟姐妹中的 7 名仍未出现病例定义的机会性感染。最终，只有5名患者死于儿童期，其余36名患者都安然无恙。因此，对于患有机会性分枝杆菌病或沙门氏菌病的儿童，应考虑诊断为 IL-12Rβ1 缺乏症；先证者的健康兄弟姐妹和选定的结核病病例也应进行调查。由于对感染具有广泛的抵抗力以及感染的外显率低和良好的结果，因此总体预后良好。出乎意料的是，人IL-12在针对除分枝杆菌和沙门氏菌之外的大多数微生物的保护性免疫中是多余的。此外，在许多个体中，IL-12 对于对分枝杆菌和沙门氏菌的初级免疫是多余的，而对于大多数个体对分枝杆菌但对沙门氏菌的次级免疫来说是多余的。
The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
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影响因子：
15.9
作者：
Jouanguy, E;Dupuis, S;Casanova, JL
通讯作者：
Casanova, JL
影响因子：
5.3
作者：
den Dunnen, JT;Antonarakis, E
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Antonarakis, E
影响因子：
15.3
作者：
Cooper, AM;Magram, J;Ferrante, J;Orme, IM
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Orme, IM
影响因子：
3.6
作者：
Aksu, G;Tirpan, C;Kutukculer, N
通讯作者：
Kutukculer, N
影响因子：
2.3
作者：
Carr, JA;Rogerson, JA;Nash, AA
通讯作者：
Nash, AA