Factor H Autoantibodies

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What is Factor H?

Factor H is a soluble complementary glycoprotein present in the blood plasma that serves the primary function of controlling the alternative pathway in blood and maintaining homeostasis. In vitro experiments have also demonstrated factor H to have anti-thrombotic properties.

A lot of genetic and structural information has been generated in the past decade to understand the functional domains responsible for the activities of factor H. This, in turn, has aided in extensive study of the molecular basis of many diseases associated with factor H deficiency.

Deficiency in this factor can lead to various genetic or acquired diseases such as atypical hemolytic uremic syndrome (aHUS) and membranoproliferative glomerulonephritis. Impaired functional activity of factor H is more frequently associated with renal diseases.

Factor H (FH) Autoantibodies and its Role in Diseases

aHUS is a rare form of thrombotic microangiopathy that causes dysregulation of the alternative pathway controlled by the complement factor H giving rise to FH autoantibodies. aHUS is associated with homozygous deletion of the complement factor H related 1 (CFHR1) gene and the CFHR3 gene. This disorder is primarily seen in children aged between 9 and 13 years but also affects adults. However, the severity of HUS caused by anti-factor H autoantibodies is much higher than the HUS caused by E. coli.

Apart from aHUS, FH autoantibodies have been associated with many other diseases such as age-related macular degeneration, immunoglobulin (Ig) nephropathy, and C3 glomerulopathy.

Screening for FH Autoantibodies

Many methods of enzyme-linked immunosorbent assay (ELISA) are employed to detect FH autoantibodies. Of the various ELISA methods, the Paris method is recommended as this method aids consistent comparison across diagnostic centers. The Paris method adopts a standard arbitrary unit scale that allows for longitudinal analysis of FH autoantibodies in a disease. This method also helps in understanding and establishing the importance of different FH autoantibody titers in aHUS.

Screening of FH autoantibodies at the onset of a disease can improve prognosis by enabling early application of appropriate therapies.

Therapeutic Intervention for FH Autoantibody-Associated Disease

Treatment of aHUS usually involves the use of humanized monoclonal antibody. Interventional studies such as plasma exchange along with the administration of immunosuppressive agents have been conducted and have been successful in bringing down the antibody titers especially in aHUS. There was significant improvement in the renal survival and outcome especially in pediatric patients with aHUS. This is further supported by a study conducted by Kwon et al. in which the first successful renal transplantation was carried out in a patient with aHUS.

In this study too, plasma exchange was carried out to bring down the FH antibody levels along with the administration of rituximab for a period of four months to maintain low antibody levels.

With many diseases known to be linked to factor H mutation or dysregulation, it is imperative to screen patients for FH autoantibody titers, especially in case of familial C3 glomerulopathies and aHUS.

Further Reading

Last Updated: Feb 26, 2019

Deepthi Sathyajith

Written by

Deepthi Sathyajith

Deepthi spent much of her early career working as a post-doctoral researcher in the field of pharmacognosy. She began her career in pharmacovigilance, where she worked on many global projects with some of the world's leading pharmaceutical companies. Deepthi is now a consultant scientific writer for a large pharmaceutical company and occasionally works with News-Medical, applying her expertise to a wide range of life sciences subjects.


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