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C4 glomerulopathy

Authors
Sanjeev Sethi, MD, PhD
Fernando C Fervenza, MD, PhD
Section Editors
Richard J Glassock, MD, MACP
Brad H Rovin, MD
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Glomerulonephritis (GN) can result from a number of pathogenic processes that cause glomerular deposition of immune complexes and/or complement [1]. Immune complex-mediated GN (due, for example, to chronic infections such as hepatitis C virus) is characterized by deposits of immunoglobulin, often accompanied by deposition of complement that includes C3 and/or C4 and, in some cases, C1q. Deposition of C3, C4, and C1q in immune complex-mediated GN is likely due to activation of the classical pathway of complement.

On the other hand, complement-mediated GN is usually characterized by deposition of C3 with minimal or no immunoglobulin deposits. The prototype of complement-mediated GN is C3 glomerulopathy, which includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both C3GN and DDD result from overactivation of the alternative pathway of complement [2-5]. In C3 glomerulopathy, C4 is typically absent on immunofluorescence microscopy [6].

In 2014, a new type of complement-mediated GN was identified that was characterized by deposition of C4 in the absence of C3, C1q, and immunoglobulin. This disorder was called C4 dense deposit disease (abbreviated as C4 DDD; if there were dense C4 deposits along the glomerular basement membrane documented by electron microscopy) or C4 glomerulonephritis (abbreviated as C4GN; if there were C4 deposits primarily in the mesangium with few capillary wall deposits). Thus, complement-mediated GN can be subdivided into C3 glomerulopathy (C3GN and DDD) and C4 glomerulopathy (C4GN and C4 DDD) (figure 1).

C4 DDD and C4GN are discussed in this topic. C3 glomerulopathy and immune complex-mediated GN are presented elsewhere. (See "C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis" and "Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis", section on 'Immune complex-mediated MPGN'.)

PATHOGENESIS

Although the pathogenesis of C4 glomerulopathy has yet to be defined, overactivity of the lectin pathway of complement activation is likely involved. The lectin pathway, like the classical (immunoglobulin-dependent) pathway, activates C2 and C4 (and not C1q), but it does so without involvement of antibodies. Detailed discussions of the lectin pathway of complement activation are presented elsewhere. (See "Overview and clinical assessment of the complement system" and "Complement pathways", section on 'Lectin pathway'.)

     

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Literature review current through: Nov 2016. | This topic last updated: Mon Mar 28 00:00:00 GMT+00:00 2016.
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