Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models.
Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models.
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DOI：
10.3389/fimmu.2023.1304086
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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在输血红细胞(RBC)期间，受者同时接触ABO和非ABO‘次要’抗原。RBC供体单位和受体RBC通常不匹配非ABO抗原。因此，受者暴露于许多RBC同种异体抗原，可导致RBC同种异体抗体的产生和随后的临床显著溶血。红细胞同种异体抗体也极大地限制了为受者提供相容的红细胞单位。先前的研究表明，在炎症反应和自身免疫性疾病患者中，红细胞同种异体免疫的频率增加。尽管如此，对自身免疫患者同种异体免疫反应的机制还不是很清楚。超过一半的成人系统性红斑狼疮患者产生1型干扰素(干扰素α/β)并表达干扰素α/β刺激基因(ISGs)。此前，我们报道了干扰素α/β促进普里斯坦小鼠模型的红细胞同种异体免疫反应，该模型发展为狼疮样表型，依赖干扰素α/β信号。然而，目前尚不清楚干扰素α/β或狼疮样表型是否能在狼疮模型中诱导同种免疫。因此，我们通过检测干扰素α/β非依赖性(MRL-α/β)和干扰素α/β依赖性(Pristane)狼疮模型中的同种免疫反应，验证了干扰素LPR促进狼疮红细胞同种免疫反应的假设。虽然Pristane治疗显著诱导干扰素刺激基因(ISGs)，但MRL-LPR小鼠产生的水平明显低于未治疗的WT小鼠。输注表达KEL抗原的小鼠红细胞，可使经Pristane处理的WT小鼠产生抗KEL的Ig G。然而，MRL-LPR小鼠产生的抗Kel抗体水平最低。重组干扰素α治疗mrllpr小鼠可显著增强同种异体免疫。总之，结果表明，临床前模型中的狼疮样表型不足以诱导红细胞同种异体抗体的产生，干扰素α/β基因特征可能与狼疮小鼠模型中的红细胞同种免疫反应有关。如果这些发现扩展到替代的临床前模型和临床研究，表达干扰素α/β基因特征的系统性红斑狼疮患者可能会增加患红细胞同种异体抗体的风险，并可能从更个性化的输血方案中受益。
During transfusion of red blood cells (RBCs), recipients are exposed to both ABO and non-ABO ‘minor’ antigens. RBC donor units and recipient RBCs are not routinely matched for non-ABO antigens. Thus, recipients are exposed to many RBC alloantigens that can lead to RBC alloantibody production and subsequent clinically significant hemolysis. RBC alloantibodies also significantly limit the provision of compatible RBC units for recipients. Prior studies indicate that the frequency of RBC alloimmunization is increased during inflammatory responses and in patients with autoimmune diseases. Still, mechanisms contributing to alloimmune responses in patients with autoimmunity are not well understood. More than half of adult patients with systemic lupus erythematosus (SLE) produce type 1 interferons (IFNα/β) and express IFNα/β stimulated genes (ISGs). Previously, we reported that IFNα/β promote RBC alloimmune responses in the pristane mouse model, which develops a lupus-like phenotype that is dependent on IFNα/β signaling. However, it is unclear whether IFNα/β or the lupus-like phenotype induces alloimmunization in lupus models. Therefore, we tested the hypothesis that IFNα/β promotes RBC alloimmune responses in lupus by examining alloimmune responses in IFNα/β-independent (MRL-lpr) and IFNα/β-dependent (pristane) lupus models. Whereas pristane treatment significantly induced interferon-stimulated genes (ISGs), MRL-lpr mice produced significantly lower levels that were comparable to levels in untreated WT mice. Transfusion of murine RBCs that express the KEL antigen led to anti-KEL IgG production by pristane-treated WT mice. However, MRL-lpr mice produced minimal levels of anti-KEL IgG. Treatment of MRL-lpr mice with recombinant IFNα significantly enhanced alloimmunization. Collectively, results indicate that a lupus-like phenotype in pre-clinical models is not sufficient to induce RBC alloantibody production, and IFNα/β gene signatures may be responsible for RBC alloimmune responses in lupus mouse models. If these findings are extended to alternate pre-clinical models and clinical studies, patients with SLE who express an IFNα/β gene signature may have an increased risk of developing RBC alloantibodies and may benefit from more personalized transfusion protocols.
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影响因子：
7.3
作者：
Lee JY;Madany E;El Kadi N;Pandya S;Ng K;Yamashita M;Jefferies CA;Gibb DR
通讯作者：
Gibb DR
影响因子：
4.9
作者：
Rönnblom L;Alm GV
通讯作者：
Alm GV
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
--
作者：
Kirou, KA;Lee, C;Crow, MK
通讯作者：
Crow, MK
影响因子：
20.3
作者：
Hudson, Krystalyn E.;Lin, Eugene;Zimring, James C.
通讯作者：
Zimring, James C.