Gardinali M, Conciato L, Cafaro C, Crosignani A, Battezzati P M, Agostoni A, Podda M
Institute of Internal Medicine, IRCCS Ospedale Policlinico, Milan, Italy.
Clin Immunol Immunopathol. 1998 Jun;87(3):297-303. doi: 10.1006/clin.1998.4542.
There is controversial evidence suggesting that the classical pathway of complement system is chronically activated in primary biliary cirrhosis (PBC) and that complement activation may be important in development of bile duct injury. We have reevaluated this issue by measuring by-products of complement activation such as C4a, C3a, Bb, and terminal complement complexes (SC5b-9) in plasma of 44 PBC patients with sensitive methods not previously used to detect complement activation in this disease. Age-matched healthy women and patients with chronic hepatitis of different etiology were studied as controls. We found that PBC patients have normal C4a concentrations. This finding argues strongly against chronic classical pathway activation. Although a minor increase of C3a levels was observed in a minority of PBC patients, the C3a/C3 ratio, an index used to evaluate the extent of native protein conversion, was remarkably similar in all groups. Potentially lytic terminal complement complexes were not increased. PBC patients had normal Bb plasma levels, indicating that the alternative pathway is also not activated. C3 concentration was higher in PBC patients than in healthy subjects and in chronic hepatitis patients, particularly in the early stages of the disease. C3 and C4 concentrations became lower in PBC and chronic hepatitis with the progression of the disease. The increase of C3 concentration in PBC does not reflect liver inflammation, since serum levels of C-reactive protein are normal. We found high serum C3 levels in patients with rare chronic cholestatic syndromes without superimposed infections and observed that serum C3 levels paralleled those of bilirubin in a patient with benign recurrent intrahepatic cholestasis. In conclusion, our data indicate that complement is not activated in PBC and that the increase of serum C3 levels is related to cholestasis.
有争议性的证据表明，补体系统的经典途径在原发性胆汁性肝硬化（PBC）中被慢性激活，且补体激活可能在胆管损伤的发展中起重要作用。我们通过用此前未用于检测该疾病补体激活的灵敏方法，测量44例PBC患者血浆中补体激活的副产物，如C4a、C3a、Bb和终末补体复合物（SC5b-9），对这一问题进行了重新评估。将年龄匹配的健康女性和不同病因的慢性肝炎患者作为对照进行研究。我们发现PBC患者的C4a浓度正常。这一发现有力地反驳了慢性经典途径激活的观点。虽然在少数PBC患者中观察到C3a水平有轻微升高，但用于评估天然蛋白转化程度的指标C3a/C3比值在所有组中都非常相似。具有潜在溶解作用的终末补体复合物并未增加。PBC患者的Bb血浆水平正常，表明替代途径也未被激活。PBC患者的C3浓度高于健康受试者和慢性肝炎患者，尤其是在疾病早期。随着疾病进展，PBC和慢性肝炎患者的C3和C4浓度降低。PBC患者中C3浓度的升高并不反映肝脏炎症，因为C反应蛋白的血清水平正常。我们在无叠加感染的罕见慢性胆汁淤积综合征患者中发现血清C3水平较高，并观察到在一名良性复发性肝内胆汁淤积患者中，血清C3水平与胆红素水平平行。总之，我们的数据表明PBC中补体未被激活，血清C3水平的升高与胆汁淤积有关。
