Bien Christian G, Bauer Jan
Epilepsy Center Bethel, Krankenhaus Mara, Bielefeld, Germany.
Neurotherapeutics. 2014 Apr;11(2):311-8. doi: 10.1007/s13311-014-0264-3.
In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody- and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.
自20世纪80年代/90年代以来，在患有免疫相关的中枢神经系统灰质疾病（包括癫痫复发）的患者中，已发现针对细胞内抗原的抗体。近年来，还发现了针对表面抗原的新抗体。在两个方面，这些抗体比针对细胞内抗原的抗体更具吸引力，其一，它们有望对免疫疗法产生更好的反应；其二，这些抗体对疾病机制的理解有很大帮助。在针对细胞内抗原的抗体介导的脑脊髓炎中，细胞毒性T细胞介导的反应似乎是神经元细胞丢失的原因，而在针对表面抗原的自身抗体介导的脑脊髓炎中，这些抗体可能是相关疾病状态下的致病因子。一方面，有人提出针对N-甲基-D-天冬氨酸受体NR1亚基的抗体可导致这些受体的内化和丢失，而不会造成任何细胞破坏。这种机制可以解释这些抗体引起的可逆性功能效应。另一方面，已注意到抗体和补体介导的破坏性作用，以及针对电压门控钾通道抗原的抗体的不可逆效应。这些新发现使得免疫疗法（最好在抗体鉴定后尽早进行）为恢复受影响患者的健康提供机会这一观点变得合理。
