Nauen David W
Department of Pathology, Johns Hopkins Hospital, Ross 512, 720 Rutland Ave, Baltimore, MD 21205.
J Crit Care. 2017 Feb;37:234-236. doi: 10.1016/j.jcrc.2016.09.016. Epub 2016 Sep 22.
Anti-N-methyl-d-aspartate-type glutamate receptor autoimmune encephalitis can arise in the setting of ovarian teratoma and often responds to resection. When it occurs in the absence of tumor, failure to respond to treatment may be more likely, and affected patients often require intensive care. To further understand the mechanisms and potential management, we present findings from an autopsy conducted on a young woman who died of refractory autoimmune encephalitis of this type. Rituximab was administered 70 days before death, and both 37 and 14 days before death, CD19 lymphocytes were only 0.1% of blood cells. Ten sessions of plasmapheresis were performed after rituximab treatment. Nonetheless, the autoantibodies were present in serum 4 days before death, demonstrating ongoing antibody production. The hippocampus and medial temporal lobe demonstrated inflammation with T cell and prominent microglial involvement, but no plasma cells or plasmablasts were found there, or anywhere in the brain, despite an extensive search. Examination of lymph node tissue identified many plasma cells along sinusoids. These findings demonstrate that the antibody-producing cells are long-lived and can reside in lymphoid tissue. Awareness of continuing antibody production, the extra-central nervous system site, the indication for cytotoxic therapy, and the potential for biopsy assessment may lead to more effective treatment.
抗N-甲基-D-天冬氨酸型谷氨酸受体自身免疫性脑炎可在卵巢畸胎瘤的情况下发生，且通常对肿瘤切除有反应。当它在无肿瘤的情况下发生时，对治疗无反应的可能性可能更高，受影响的患者通常需要重症监护。为了进一步了解其机制和潜在的治疗方法，我们展示了对一名死于这种难治性自身免疫性脑炎的年轻女性进行尸检的结果。在死亡前70天给予了利妥昔单抗，在死亡前37天和14天，CD19淋巴细胞仅占血细胞的0.1%。在利妥昔单抗治疗后进行了十次血浆置换。尽管如此，在死亡前4天血清中仍存在自身抗体，表明抗体持续产生。海马体和内侧颞叶显示出炎症，有T细胞和显著的小胶质细胞参与，但在那里或大脑的任何部位都未发现浆细胞或浆母细胞，尽管进行了广泛的搜索。对淋巴结组织的检查发现沿窦状隙有许多浆细胞。这些发现表明产生抗体的细胞寿命长，可存在于淋巴组织中。认识到抗体的持续产生、中枢神经系统外的部位、细胞毒性治疗的指征以及活检评估的可能性可能会带来更有效的治疗。
