Dense deposit disease and C3 glomerulopathy.

Area of Science:

• Nephrology
• Immunology
• Complement System Biology

Background:

• C3 glomerulopathy is defined by glomerular C3 deposition and complement alternative pathway dysregulation.
• Dense deposit disease is a subtype of C3 glomerulopathy with unique electron microscopy features.
• Clinical distinctions, natural history, and treatment outcomes of dense deposit disease versus other C3 glomerulopathies require further clarification.

Purpose of the Study:

• To review the pathophysiology of C3 glomerulopathy, focusing on complement alternative pathway dysregulation.
• To discuss evidence from human studies and animal models regarding complement dysregulation in C3 glomerulopathy.
• To explore recent findings on genetic factors, such as genomic rearrangements in complement factor H-related genes, contributing to familial C3 glomerulopathy.

Main Methods:

• Review of existing literature on C3 glomerulopathy and dense deposit disease.
• Analysis of evidence from studies on patients with C3 glomerulopathy.
• Examination of data from complement factor H-deficient animal models.

Main Results:

• Aberrant regulation of the complement alternative pathway is central to C3 glomerulopathy pathogenesis.
• Evidence from affected individuals and Cfh-deficient models supports the role of complement dysregulation.
• Genomic rearrangements in Cfh-related genes are implicated in familial C3 glomerulopathy, suggesting Cfh deregulation.

Conclusions:

• C3 glomerulopathy pathogenesis is linked to complement alternative pathway dysregulation.
• Complement factor H deregulation is a proposed mechanism in familial forms of the disease.
• Further research is needed to fully understand the clinical spectrum and treatment of dense deposit disease compared to other C3 glomerulopathies.