Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

C3 glomerulopathy

C3 glomerulopathy is a glomerular kidney disease caused by abnormal activation of the alternative complement pathway. The dominating histomorphological finding is C3 deposition. According to electron microscopy of the localization of these deposits, two subtypes can be distinguished dense deposit disease and C3 glomerulonephritis.

Classification

G cluster0 cluster1 Dense Deposit Disease (DDD) cluster2 C3 Glomerulonephritis (C3GN) s0 C3 Glomerulopythy (C3G) a2 Autoantobody DDD s0->a2 b2 Autoantibody C3GN s0->b2 a1 Genetic DDD a3 Unspecified DDD b1 Genetic C3GN b3 Unspecified C3GN
C3 glomerulopathy

Laboratory tests

General work-up

Parameter Interpretation
ANA, ANCA, Anti-GBM Autoantibodies
HIV, Hepatitis B and C Infectiousness
HDL-C, LDL-C, Chol, TG Lipids
Serum albumin und total protein nutrition/protein loss
IgG (subtypes), IgM, IgA, IgE Immunoglobulin abnormalities
Albuminuria/g Crea Urine-protein-to-creatinine ratio (UPr/Cr)

Complement-specific work-up

Parameter Interpretation
C3, C4, C3d Complement activation
CH50, APH50 total hemolytic complement activity, classical and alternative
sMAC/CD5b9 soluble membrane attack complex
C3NeF C3-convertase of the alternative pathway-(C3bBb)-autoantibodies
Factors I, B, D, H and CFHR1-5 modulators of the complement cascade
autoantibodies factor B, H, CFHR autoantibodies of modulators

In rare cases autoantibodies against C3-convertase of the classical pathway-(C4bC2b)is detectable. Also rare are atoantibodies against C3 and Non-c3NeF-autoantibodies against different components of the C3-convertase. Those antibodies, because so rare are difficult to interpret nephrologically.

Registry

Klinisches Register für C3 Glomerulopathie und Immunkomplex-vermittelte MPGN

Systematic

Glomerulonephritis
C3 glomerulopathy
C3 glomerulonephritis
ADAMTS13
C1QA
C1QB
C1QC
C3
CD46
CFB
CFD
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
DGKE
PIGA
THBD
Dense deposit disease
ADAMTS13
C1QA
C1QB
C1QC
C3
CD46
CFB
CFD
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
DGKE
PIGA
THBD
CFHR5 Nephropathy
Goodpasture syndrome
Lupus erythematosus nephritis
Membranoproliferative glomerulonephritis (MPGN)
Membranous nephropathy
Mesangioproliferative glomerulonephritis

References:

1.

Levy M et al. (1986) H deficiency in two brothers with atypical dense intramembranous deposit disease.

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2.

Brai M et al. (1988) Combined homozygous factor H and heterozygous C2 deficiency in an Italian family.

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3.

Vogt BA et al. (1995) Inherited factor H deficiency and collagen type III glomerulopathy.

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4.

Høgåsen K et al. (1995) Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

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5.

Ault BH et al. (1997) Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism.

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6.

Sánchez-Corral P et al. (2000) Molecular basis for factor H and FHL-1 deficiency in an Italian family.

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7.

None (2000) Factor H and the pathogenesis of renal diseases.

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8.

Pickering MC et al. (2002) Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H.

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9.

Hegasy GA et al. (2002) The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion.

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10.

Dragon-Durey MA et al. (2004) Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.

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11.

Abrera-Abeleda MA et al. (2006) Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease).

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12.

Licht C et al. (2006) Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel pathomechanism for dense deposit disease (MPGN II).

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13.

Servais A et al. (2007) Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome.

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14.

Nielsen HE et al. (1989) Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease.

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15.

Wyatt RJ et al. (1982) Partial H (beta 1H) deficiency and glomerulonephritis in two families.

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16.

Fijen CA et al. (1996) Heterozygous and homozygous factor H deficiency states in a Dutch family.

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17.

None (2002) Complement in glomerulonephritis.

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18.

Appel GB et al. (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): an update.

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19.

Xiao X et al. (2014) C3 glomerulopathy: the genetic and clinical findings in dense deposit disease and C3 glomerulonephritis.

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20.

Redahan L et al. (2014) Familial MPGN - a case series: a clinical description of familial membranoproliferative glomerulonephritis amongst three Irish families.

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21.

Chen Q et al. (2014) Complement factor H-related hybrid protein deregulates complement in dense deposit disease.

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22.

Barbour TD et al. (2013) Dense deposit disease and C3 glomerulopathy.

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23.

Orphanet article

Orphanet ID 329918 [^]
Update: April 29, 2019