O'Connell Elise, Rosen Lindsey B, LaRue Richard W, Fabre Valeria, Melia Michael T, Auwaerter Paul G, Holland Steven M, Browne Sarah K
Laboratory of Parasitic Diseases, NIAID, NIH, CRC B3-4141, MSC 1684, Bethesda, MD, 20892-1684, USA.
J Clin Immunol. 2014 Nov;34(8):928-32. doi: 10.1007/s10875-014-0073-9. Epub 2014 Aug 23.
Anti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia.
We studied an American-born, Caucasian female with M. avium complex infection of the subglottic mucosa and brain for underlying etiologies of infection.
Plasma was screened for anticytokine autoantibodies using a Luminex-based approach. The ability of patient plasma to block IFNγ-induced STAT1 phosphorylation in normal blood cells was evaluated by flow cytometry with intracellular staining. Plasma inhibition of IFNγ production and IFNγ-induced cytokines in normal and patient blood cells washed of autologous plasma was also evaluated.
Patient plasma contained high-titer IgG anti-IFNγ autoantibodies, primarily of the IgG1 subclass. Patient but not control plasma prevented IFNγ-induced STAT1 phosphorylation and expression of the IFNγ-inducible cytokines tumor necrosis factor (TNF) α and interleukin (IL)-12 in normal blood cells. Patient blood cells washed free of autologous plasma demonstrated normal IFNγ production and response.
Disseminated nontuberculous mycobacterial infections should always prompt immune evaluation. This first case of disseminated nontuberculous mycobacterial infection and anti-IFNγ autoantibodies in an American-born Caucasian suggests that anti-cytokine autoantibodies are not racially or regionally restricted.
抗干扰素-γ（IFNγ）自身抗体与播散性分枝杆菌感染有关，主要见于东南亚患者。
我们研究了一名在美国出生的白种女性，其声门下黏膜和脑部存在鸟分枝杆菌复合群感染，以寻找感染的潜在病因。
采用基于Luminex的方法筛查血浆中的抗细胞因子自身抗体。通过细胞内染色的流式细胞术评估患者血浆阻断正常血细胞中IFNγ诱导的信号转导和转录激活因子1（STAT1）磷酸化的能力。还评估了血浆对正常和患者血细胞中IFNγ产生及IFNγ诱导的细胞因子的抑制作用，这些血细胞已洗去自身血浆。
患者血浆中含有高滴度的IgG抗IFNγ自身抗体，主要为IgG1亚类。患者血浆而非对照血浆可阻止正常血细胞中IFNγ诱导的STAT1磷酸化以及IFNγ诱导细胞因子肿瘤坏死因子（TNF）α和白细胞介素（IL）-12的表达。洗去自身血浆后的患者血细胞显示出正常的IFNγ产生和反应。
播散性非结核分枝杆菌感染应始终促使进行免疫评估。这例在美国出生白种人中出现的播散性非结核分枝杆菌感染及抗IFNγ自身抗体的首例病例表明抗细胞因子自身抗体不受种族或地域限制。
