Department of Internal Medicine, ZGT Hospital, Almelo, the Netherlands.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Am J Kidney Dis. 2015 Apr;65(4):607-10. doi: 10.1053/j.ajkd.2014.09.026. Epub 2014 Dec 18.
A 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered autoimmune. However, the patient did not meet criteria for any of the autoimmune disorders classically associated with dRTA. She had very high antibody titers against parietal cells, intrinsic factor, and thyroid peroxidase (despite normal thyroid function). The patient consented to a kidney biopsy, and acid-base transporters, anion exchanger type 1 (AE1), and pendrin were undetectable by immunofluorescence. Indirect immunofluorescence detected diminished abundance of AE1- and pendrin-expressing intercalated cells in the kidney, as well as staining by the patient's serum of normal human intercalated cells and parietal cells expressing the adenosine triphosphatase hydrogen/potassium pump (H(+)/K(+)-ATPase) in normal human gastric mucosa. The dRTA likely is caused by circulating autoantibodies against intercalated cells, with possible cross-reactivity against structures containing gastric H(+)/K(+)-ATPase. This case demonstrates that in patients with dRTA without a classic autoimmune disorder, autoimmunity may still be the underlying cause. The mechanisms involved in autoantibody development and how dRTA can be caused by highly specific autoantibodies against intercalated cells have yet to be determined.
一位 61 岁有恶性贫血病史的女性，出现进行性肌肉无力和构音障碍。由于远端肾小管酸中毒（dRTA）导致低钾性瘫痪（血清钾 1.4 mEq/L）。在排除了几种可能的原因后，认为 dRTA 是自身免疫性的。然而，该患者不符合任何经典的与 dRTA 相关的自身免疫疾病的标准。她的壁细胞、内因子和甲状腺过氧化物酶抗体滴度非常高（尽管甲状腺功能正常）。患者同意进行肾活检，免疫荧光检测不出酸-碱转运蛋白、阴离子交换体 1（AE1）和 pendrin。间接免疫荧光检测到肾脏中的 AE1 和 pendrin 表达闰细胞的丰度减少，以及患者血清对正常人类闰细胞和表达三磷酸腺苷氢/钾泵（H(+)/K(+)-ATPase）的壁细胞的染色。dRTA 可能是由针对闰细胞的循环自身抗体引起的，可能与含有胃 H(+)/K(+)-ATPase 的结构发生交叉反应。该病例表明，在没有经典自身免疫疾病的 dRTA 患者中，自身免疫仍可能是潜在原因。自身抗体产生的机制以及 dRTA 如何由针对闰细胞的高度特异性自身抗体引起，仍有待确定。
