Abstract
Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephritic factor has been characterized by the ability to stabilize C5 convertase of the alternative pathway (C5NeF). In addition, there are autoantibodies against assembled C3/C5 convertase of the classical and lectin pathways (C4NeF). These autoantibodies have been mainly associated with kidney diseases, like C3 glomerulopathy and immune complex-associated-membranoproliferative glomerulonephritis. Other clinical situations where these autoantibodies have been observed include infections and autoimmune disorders such as systemic lupus erythematosus and acquired partial lipodystrophy. C3 hypocomplementemia is a common finding in all patients with nephritic factors. The methods to measure nephritic factors are not standardized, technically complex, and lack of an appropriate quality control. This review will be focused in the description of the mechanism of action of the three known nephritic factors (C3NeF, C4NeF, and C5NeF), and their association with human diseases. Moreover, we present an overview regarding the diagnostic tools for its detection, and the main therapeutic approach for the patients with nephritic factors.
Highlights
The complement system is a complex molecular system with fundamental roles in apoptotic cell clearance, immune complex elimination, defense against infections, and modulation of adaptive immunity [1]
The complement cascade is activated by three distinct mechanisms: the classical pathway (CP), the lectin pathway (LP) and the alternative pathway (AP) (Figure 1)
nephritic factor (NF) were first described in 1969, based on the observation that the serum from a patient with membranoproliferative glomerulonephritis (MPGN) and hypocomplementemia broke down C3 when it was mixed with normal human serum [9, 10]
Summary
The complement system is a complex molecular system with fundamental roles in apoptotic cell clearance, immune complex elimination, defense against infections, and modulation of adaptive immunity [1]. There is a complement positive regulator, called properdin (P), which can bind to the C3bBb complex inducing an increase of his half-life [1, 2] Such as happened in CP and LP, generation of the AP C5 convertase (C3bBbC3b) cleaves C5 and ends in MAC formation [1, 2]. The convertase complexes dissociate spontaneously in a few minutes, a process that is critical to prevent autologous tissue injury To prevent this damage, there is a group of soluble complement regulatory proteins (Factor H (FH), Factor I (FI) and C4BP) and membrane proteins (MCP/CD46, DAF/CD55, CR1/CD35, and CD59) with crucial roles in accelerate C3/C5 convertase dissociation, and/or inactivate C3b by proteolytic cleavage [4, 5] (Figure 1). Of autoantibodies against complement components, such as nephritic factors (NFs), are associated with several diseases, including C3 glomerulopathy (C3G), membranoproliferative glomerulonephritis (MPGN), acquired partial lipodystrophy (APL) or Systemic Lupus Erythematosus (SLE) [6,7,8]
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