Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

Høgåsen, K; Jansen, J. H.; Mollnes, Tom Eirik; Hovdenes, Jan; Harboe, Morten

doi:10.1172/jci117751

Cited by 200 publications

(149 citation statements)

References 29 publications

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“…In addition, type II MPGN is associated with homozygous deficiency of factor H (63), as well as inhibitory serum Abs to factor H (65). Homozygous deficiency of factor H in both pigs (66) and mice (67) also leads to the development of MPGN. However, crossing the factor H-deficient mice with factor B-deficient mice rescues the offspring from this phenotype (67), confirming that activation of the alternative pathway is critical to the pathogenesis of disease in these mice.…”

Section: Type II Membranoproliferative Glomerulonephritis (Mpgn)mentioning

confidence: 99%

The Central Role of the Alternative Complement Pathway in Human Disease

Thurman

Holers

2006

The Journal of Immunology

389

350

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The complement system is increasingly recognized as important in the pathogenesis of tissue injury in vivo following immune, ischemic, or infectious insults. Within the complement system, three pathways are capable of initiating the processes that result in C3 activation: classical, alternative, and lectin. Although the roles that proinflammatory peptides and complexes generated during complement activation play in mediating disease processes have been studied extensively, the relative contributions of the three activating pathways is less well understood. Herein we examine recent evidence that the alternative complement pathway plays a key and, in most instances, obligate role in generating proinflammatory complement activation products in vivo. In addition, we discuss new concepts regarding the mechanisms by which the alternative pathway is activated in vivo, as recent clinical findings and experimental results have provided evidence that continuous active control of this pathway is necessary to prevent unintended targeting and injury to self tissues.

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Section: Type II Membranoproliferative Glomerulonephritis (Mpgn)mentioning

confidence: 99%

The Central Role of the Alternative Complement Pathway in Human Disease

Thurman

Holers

2006

The Journal of Immunology

389

350

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“…The role of complement activation has been shown to play an important part in the pathogenesis of acute inflammatory conditions like I/R-injury (91), meconium aspiration syndrome (MAS) (92), trauma (93) and sepsis (94). In addition complement is involved in chronic inflammatory diseases like glomerulonephritis and rheumatoid arthritis (95)(96)(97). …”

Section: Complement and Inflammationmentioning

confidence: 99%

Candidate inhibitors of porcine complement

Thorgersen¹,

Ghebremariam²,

Thurman³

et al. 2007

Molecular Immunology

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“…Moreover, some cancer cell surfaces (20,21) and pathogenic microorganisms (22)(23)(24)(25)(26)(27) have developed immune evasion strategies whereby they bind factor H, thus disguising themselves as self cells and escaping elimination by the alternative pathway of complement. In a factor H-deficient line of pigs, homozygous individuals die soon after birth from complement-mediated acute renal failure (28), and factor H-deficient mice develop membranoproliferative glomerulonephritis, which was shown to be alternative pathway dependent (19).…”

mentioning

confidence: 99%

Critical Role of the C-Terminal Domains of Factor H in Regulating Complement Activation at Cell Surfaces

Ferreira

Herbert

Hocking

et al. 2006

The Journal of Immunology

133

109

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The plasma protein factor H primarily controls the activation of the alternative pathway of complement. The C-terminal of factor H is known to be involved in protection of host cells from complement attack. In the present study, we show that domains 19–20 alone are capable of discriminating between host-like and complement-activating cells. Furthermore, although factor H possesses three binding sites for C3b, binding to cell-bound C3b can be almost completely inhibited by the single site located in domains 19–20. All of the regulatory activities of factor H are expressed by the N-terminal four domains, but these activities toward cell-bound C3b are inhibited by isolated recombinant domains 19–20 (rH 19–20). Direct competition with the N-terminal site is unlikely to explain this because regulation of fluid phase C3b is unaffected by domains 19–20. Finally, we show that addition of isolated rH 19–20 to normal human serum leads to aggressive complement-mediated lysis of normally nonactivating sheep erythrocytes and moderate lysis of human erythrocytes, which possess membrane-bound regulators of complement. Taken together, the results highlight the importance of the cell surface protective functions exhibited by factor H compared with other complement regulatory proteins. The results may also explain why atypical hemolytic uremic syndrome patients with mutations affecting domains 19–20 can maintain complement homeostasis in plasma while their complement system attacks erythrocytes, platelets, endothelial cells, and kidney tissue.

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Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.

Cited by 200 publications

References 29 publications

The Central Role of the Alternative Complement Pathway in Human Disease

The Central Role of the Alternative Complement Pathway in Human Disease

Candidate inhibitors of porcine complement

Critical Role of the C-Terminal Domains of Factor H in Regulating Complement Activation at Cell Surfaces

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