Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Marseille, France.
Am J Nephrol. 2012;35(2):134-40. doi: 10.1159/000335375. Epub 2012 Jan 13.
We report on 3 cases of membranoproliferative glomerulonephritis associated with mixed cryoglobulin in patients with hepatitis C virus (HCV) antibodies but a negative blood viral load. These cases explore the pathogenesis of the renal disease.
We searched for occult HCV infection in peripheral blood mononuclear cells, cryoprecipitate, bone marrow cells, and glomeruli using ultrasensitive PCR assays and immunohistochemistry. We also looked for infraclinical B cell lymphoma by computed tomodensitometry, bone marrow aspiration and biopsy, and lymphocyte typing.
By PCR assays, we did not evidence occult hepatitis C infection in peripheral blood mononuclear cells, bone marrow cells, or cryoprecipitates. In the only patient with available kidney specimen, we evidenced HCV-NS3 antigen in glomeruli. HCV-associated lymphoma was excluded, but mild polyclonal B lymphocytosis was present in the 3 patients. Remission occurred spontaneously in 1 patient, and in another patient it occurred after rituximab treatment. The third patient was lost to follow-up.
In patients with hepatitis C-negative viral load, membranoproliferative glomerulonephritis could be induced by the persistence of HCV antigen in the kidney but not in hematopoietic cells. Nonlymphomatous B cell proliferation may also be induced by chronic viral stimulation.
我们报告了 3 例丙型肝炎病毒（HCV）抗体阳性但血液病毒载量阴性的患者伴混合冷球蛋白血症的膜增生性肾小球肾炎，这些病例探索了肾脏病的发病机制。
我们使用超敏 PCR 检测和免疫组化检测外周血单个核细胞、冷沉淀物、骨髓细胞和肾小球中的隐匿性 HCV 感染。我们还通过计算机断层扫描、骨髓抽吸和活检以及淋巴细胞分型检查寻找亚临床 B 细胞淋巴瘤。
通过 PCR 检测，我们在外周血单个核细胞、骨髓细胞或冷沉淀物中均未发现隐匿性 HCV 感染。在唯一有可用肾脏标本的患者中，我们在肾小球中发现了 HCV-NS3 抗原。排除了 HCV 相关淋巴瘤，但 3 例患者均存在轻度多克隆 B 淋巴细胞增多。1 例患者自发缓解，另 1 例患者在利妥昔单抗治疗后缓解。第 3 例患者失访。
在 HCV 病毒载量阴性的患者中，肾脏中 HCV 抗原的持续存在而非造血细胞中的持续存在可能导致膜增生性肾小球肾炎。慢性病毒刺激也可能诱导非淋巴瘤性 B 细胞增殖。
