PDF iconKidney Disease Testing Requisition Form (Effective beginning January 3, 2017)

The Clinical Diagnostics Service of the Molecular Otolaryngology & Renal Research Laboratories is a CLIA-approved, Joint Commission-accredited diagnostic laboratory.

Factor H Autoantibodies
Dense Deposit Disease (DDD, aka Membranoproliferative Glomerulonephritis Type II, MPGNII)

Factor H autoantibodies have been associated with DDD (Meri, et al., 1992). In patients with DDD, these autoantibodies bind to and block the N-terminal region of the Factor H protein, which compromises its fluid-phase regulatory function.

Atypical Hemolytic-Uremic Syndrome
Factor H autoantibodies are identified in ~10% patients with aHUS (Dragon-Durey, et al., 2005, Moore, et al., 2010). Most but not all patients with aHUS who develop Factor H autoantibodies are homozygous for a known polymorphism, del(CFHR3-CFHR1). Homozygosity for this deletion is seen in 15% of patients with aHUS as compared to 5% of controls of northern European ancestry (Zipfel, et al., 2007, Skerka, et al., 2009). The Factor H autoantibodies in aHUS patients bind to and block the C-terminal region of the Factor H protein, which interferes with its surface regulatory function (Józsi, et al., 2007).

Indications for screening
Screening is appropriate for patients with aHUS and biopsy-proven DDD.

MORL screening methodology
Enzyme Linked Immuno-Sorbent Assay (ELISA) is used to assay the presence of Factor H autoantibodies (Dragon-Durey, et al., 2005, Józsi, et al., 2007, Moore, et al., 2010).

Turnaround time
Turnaround time is ~2 weeks.

Sample Required
1 ml frozen serum (see testing requisition for specimen handling).

Cost & CPT Codes
See the MORL testing menu

Web sites

Kidneeds (not-for-profit foundation dedicated to the cure of DDD)
http://www.healthcare.uiowa.edu/kidneeds/ 

Foundation for Children with Atypical HUS
http://www.atypicalhus.50megs.com/index.html

References

Dragon-Durey, M., et al..: Anti-Factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005 Feb;16(2):555-63.
PubMed ID: 15590760

Józsi, M., et al.: Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome. Blood. 2007 Sep 1;110(5):1516-8.
PubMed ID: 17495132

Meri, S., et al.: Activation of the alternative pathway of complement by monoclonal lambda light chains in membranoproliferative glomerulonephritis. J Exp Med. 1992 Apr 1;175(4):939-50.
PubMed ID: 1532415

Moore, I., et al.: Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood. 2010 Jan 14;115(2):379-87.
PubMed ID: 19861685

Skerka, C., et al.: Autoantibodies in haemolytic uraemic syndrome (HUS). Thromb. Haemost. 101, 227–232 (2009).
PubMed ID: 19190803

Zipfel, P., et al.: Deletion of Complement Factor H–Related Genes CFHR1 and CFHR3 Is Associated with Atypical Hemolytic Uremic Syndrome. PLoS Genet. Mar 16;3(3):e41 2007.
PubMed ID: 17367211