Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency and affect recognition functions

Józsi, Mihály; Strobel, Stefanie; Zipfel, S.; Richter, Heiko; Heinen, Stefan; Uzonyi, Barbara; Edey, Matthew; Routledge, Danny; Strain, Lisa; Hughes, Anne E.; Goodship, Judith A.; Goodship, Timothy H.J.; Licht, Christoph; Zipfel, Peter F.; Skerka, Christine

doi:10.1016/j.molimm.2007.06.040

Cited by 4 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cutoff level for CFH antibody positivity for ELISA in this study is 100 AU/ml. appears to be a good treatment option for patients with CFH antibody-associated aHUS (25,26,(29)(30)(31)(32)(33)(35)(36)(37).…”

Section: Homozygousmentioning

confidence: 99%

“…Antibodies against CFH have been reported in patients with aHUS (25)(26)(27). These antibodies were shown to induce functional CFH deficiency (25)(26)(27)(28) by binding to its C-terminal region and thereby reducing its regulatory function.…”

Section: Introductionmentioning

confidence: 99%

“…These antibodies were shown to induce functional CFH deficiency (25)(26)(27)(28) by binding to its C-terminal region and thereby reducing its regulatory function. CFHR1 was shown to neutralize CFH antibodies in patients with aHUS (28).…”

Section: Introductionmentioning

confidence: 99%

“…Few descriptive reports on clinical and biologic data and treatments for CFH antibody-positive aHUS have been published (25,26,(29)(30)(31)(32)(33)(35)(36)(37). This study sought to evaluate the frequency of deletions in the CFHR1-5 genes and the presence of CFH antibodies in pediatric patients with aHUS and in healthy blood donors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Hofer¹,

Janecke

Zimmerhackl³

et al. 2013

Clinical Journal of the American Society of Nephrology

125

108

View full text Add to dashboard Cite

SummaryBackground and objectives This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.Design, setting, participants, & measurements A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA. Questionnaires were administered to evaluate the clinical and laboratory data.Results Homozygous deletion in CFHR1 was detected in 32% of the patients with aHUS tested, compared with 2.5% of controls (P,0.001). CFH antibodies were present in 25% of the patients and none of the controls. CFH antibodies were detected in 82% of patients with homozygous CFHR1 gene deletion and in 6% of patients without. CFH antibody-positive patients with aHUS showed a significantly lower platelet nadir at disease onset and significantly less frequent involvement of the central nervous system than did antibody-negative patients. Antibody-positive patients also received plasma therapy more often.Conclusion Homozygous deletion in CFHR1 is strongly associated with occurrence of CFH antibodies in pediatric patients with aHUS. However, despite this apparent genetic disease predisposition, it cannot be considered an exclusive cause for aHUS. Initial presentation of Shiga toxin-negative HUS with severe thrombocytopenia and no central nervous system complications in pediatric patients is especially suspicious for CFH antibody aHUS.

show abstract

Section: Homozygousmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Hofer¹,

Janecke

Zimmerhackl³

et al. 2013

Clinical Journal of the American Society of Nephrology

125

108

View full text Add to dashboard Cite

show abstract

“…The biological role, if any, of factor H‐related proteins remains unclear. This deletion is associated with the presence of anti‐factor H antibodies [109] and these antibodies appear to affect the recognition functions of factor H [109,110]. However, how this deletion predisposes to the formation of anti‐factor H antibodies is unknown.…”

Section: Unanswered Questionsmentioning

confidence: 99%

Translational Mini-Review Series on Complement Factor H: Renal diseases associated with complement factor H: novel insights from humans and animals

Pickering¹,

Cook

2008

Clinical and Experimental Immunology

166

156

View full text Add to dashboard Cite

SummaryFactor H is the major regulatory protein of the alternative pathway of complement activation. Abnormalities in factor H have been associated with renal disease, namely glomerulonephritis with C3 deposition including membranoproliferative glomerulonephritis (MPGN) and the atypical haemolytic uraemic syndrome (aHUS). Furthermore, a common factor H polymorphism has been identified as a risk factor for the development of age-related macular degeneration. These associations suggest that alternative pathway dysregulation is a common feature in the pathogenesis of these conditions. However, with respect to factor H-associated renal disease, it is now clear that distinct molecular defects in the protein underlie the pathogenesis of glomerulonephritis and HUS. In this paper we review the associations between human factor H dysfunction and renal disease and explore how observations in both spontaneous and engineered animal models of factor H dysfunction have contributed to our understanding of the pathogenesis of factor H-related renal disease.

show abstract

The Factor H protein family: The switchers of the complement alternative pathway

Lucientes

Márquez-Tirado

Jorge

2022

Immunological Reviews

View full text Add to dashboard Cite

The factor H (FH) protein family is emerging as a complex network of proteins controlling the fate of the complement alternative pathway (AP) and dictating susceptibility to a wide range of diseases including infectious, inflammatory, autoimmune, and degenerative diseases and cancer. Composed, in man, of seven highly related proteins, FH, factor H-like 1, and 5 factor H-related proteins, some of the FH family proteins are devoted to down-regulating the AP, while others exert an opposite function by promoting AP activation. Recent findings have provided insights into the molecular mechanisms defining their biological roles and their pathogenicity, illustrating the relevance that the balance between the regulators and the activators within this protein family has in defining the outcome of complement activation on cell surfaces. In this review we will discuss the emerging roles of the factor H protein family, their impact in the complement cascade, and their involvement in the pathogenesis of complementmediated diseases associated with the AP dysregulation.

show abstract

Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency and affect recognition functions

Cited by 4 publications

References 0 publications

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Translational Mini-Review Series on Complement Factor H: Renal diseases associated with complement factor H: novel insights from humans and animals

The Factor H protein family: The switchers of the complement alternative pathway

Contact Info

Product

Resources

About