Varade W S, Forristal J, West C D
Children's Hospital Research Foundation, Cincinnati, OH.
Am J Kidney Dis. 1990 Sep;16(3):196-206. doi: 10.1016/s0272-6386(12)81018-3.
Complement profiles on 22 hypocomplementemic patients with membranoproliferative glomerulonephritis (MPGN) type I, on 11 with MPGN II, and on 16 with MPGN III, gave evidence that the nephritic factor of the amplification loop (NFa) is responsible for the hypocomplementemia in MPGN II and the nephritic factor of the terminal pathway (NFt) for the hypocomplementemia in MPGN III. In contrast, in MPGN I, there was evidence for three complement-activating modalities, NFa, NFt, and immune complexes. As a result, four different patterns of complement activation were seen. NFa, found in MPGN II, produces a complement profile characterized mainly by C3 depression. In addition, four of seven (57%) severely hypocomplementemic MPGN II patients (C3 less than 30 mg/dL) had slightly depressed levels of factor B, and one of seven (14%) of properdin, but in all the C5 concentration was normal. In contrast, all eight severely hypocomplementemic patients with MPGN II had depressed C5 and properdin levels, and six of eight (75%) depressed levels of C6, C7, and/or C9. Of eight MPGN III patients with moderate hypocomplementemia, 50% had depressed C5 and properdin levels and the remainder, depressed C3 only. This spectrum of profiles is most likely produced by varying concentrations of NFt. In MPGN I, nine of 23 (39%) had a profile indicating only classical pathway activation; seven of 23 (39%), a pattern compatible with NFt alone; four of 23 (9%), evidence for both classical pathway activation and NFt; and three of 23 (13%), a pattern compatible with NFa. The unique multifactorial origin of the hypocomplementemia in MPGN I, often giving evidence of classical pathway activation, together with previously reported differences in glomerular morphology and clinical features at onset, makes it distinct from MPGN III. Depressed C8 levels were found to some extent in all hypocomplementemic states. The levels were uncommonly depressed in patients with NFa, most markedly depressed with NFt, and moderately reduced with classical pathway activation. The cause is not known. Diagnostically, profiles showing classical pathway activation and low levels of C6, C7, and/or C9 are specific for MPGN I. Those showing only classical activation are likewise diagnostic of MPGN I if systemic lupus erythematosus (SLE) and chronic bacteremia are ruled out.
对22例I型膜增生性肾小球肾炎（MPGN）、11例II型MPGN和16例III型MPGN的低补体血症患者的补体谱分析表明，扩增环肾炎因子（NFa）是II型MPGN低补体血症的原因，终末途径肾炎因子（NFt）是III型MPGN低补体血症的原因。相比之下，在I型MPGN中，有证据表明存在三种补体激活方式，即NFa、NFt和免疫复合物。结果发现了四种不同的补体激活模式。在II型MPGN中发现的NFa产生的补体谱主要特征是C3降低。此外，7例严重低补体血症的II型MPGN患者中有4例（57%）（C3低于30mg/dL）因子B水平略有降低，7例中有1例（14%）备解素水平降低，但所有患者的C5浓度均正常。相比之下，所有8例严重低补体血症的II型MPGN患者的C5和备解素水平均降低，8例中有6例（75%）C6、C7和/或C9水平降低。8例中度低补体血症的III型MPGN患者中，50%的患者C5和备解素水平降低，其余患者仅C3降低。这种补体谱很可能是由不同浓度的NFt产生的。在I型MPGN中，23例中有9例（39%）的补体谱仅表明经典途径激活；23例中有7例（39%）的模式仅与NFt相符；23例中有4例（9%）有经典途径激活和NFt的证据；23例中有3例（13%）的模式与NFa相符。I型MPGN低补体血症独特的多因素起源，常显示经典途径激活的证据，以及先前报道的发病时肾小球形态和临床特征的差异，使其有别于III型MPGN。在所有低补体血症状态下均在一定程度上发现C8水平降低。在NFa患者中C8水平通常不降低，在NFt患者中C8水平降低最明显，在经典途径激活时C8水平中度降低。原因尚不清楚。在诊断方面，显示经典途径激活且C6、C7和/或C9水平低的补体谱对I型MPGN具有特异性。如果排除系统性红斑狼疮（SLE）和慢性菌血症，仅显示经典激活的补体谱同样可诊断I型MPGN。
