Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Cells. 2021 Jun 11;10(6):1471. doi: 10.3390/cells10061471.
Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term.
We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease.
After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration.
In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.
自身免疫性肝炎（AIH）是一种慢性自身免疫性炎症性疾病，通常需要终身免疫抑制。治疗停止后频繁复发表明当前治疗方法并未恢复肝内免疫调节。其他自身免疫性疾病的研究表明，B 细胞的暂时耗竭可以改善长期疾病进展。
我们测试了单次给予抗 CD20 抗体以减少 B 细胞和 IgG 量来诱导肝内免疫耐受。我们使用实验性自身免疫性肝炎（emAIH）模型，并在疾病晚期对小鼠进行抗 CD20 治疗。
治疗后，小鼠的 B 细胞和血清 IgG 预期减少，但病理无改善。然而，所有治疗动物均表现出高度改变的血清蛋白表达模式，这是炎症和再生之间的平衡。
总之，抗 CD20 治疗并未产生临床可测量的结果，因为它在蛋白质组水平上引发了炎症和再生。这一发现表明，抗 CD20 作为 AIH 或 emAIH 的单一治疗方法无效。
