The complement system is a primary cause of numerous life-threatening diseases.
The complement system is activated in a number of infectious, inflammatory, and neoplastic diseases. A large body of research has explored the role of complement activation in the pathogenesis of these diseases
Complement mediated diseases include:
• Atypical Hemolytic Uremic Syndrome - a devastating disease that rapidly causes renal failure, hemolytic anemia, neurologic injury. Prior to the development of complement inhibitors, aHUS caused death or end-stage renal disease in >70% of patients .
• C3 Glomerulopathy – a form of renal disease that leads to end-stage renal disease in more than 50% of affected patients.
• Age-Related Macular Degeneration - the most common cause of blindness in the elderly.
In addition, the complement system contributes to the progression of a large number of other diseases including:
• Systemic lupus erythematosus (SLE).
• Other antibody-mediated systemic and autoimmune diseases.
• Antibody-mediated allograft rejection
• Alzheimer’s disease
• Multiple Sclerosis
Complement inhibitors are an important new class of drugs.
Several therapeutic complement inhibitors are in clinical use or are in development. These drugs are considered life-saving therapies for diseases that previously were not treatable [2-4].
The urgent need for complement diagnostics.
The ability to monitor disease activity is critical for the optimal treatment of all patients with autoimmune and infectious diseases. For patients with quiescent disease, the risks of immunosuppressive drugs outweigh the benefit of treatment. The dilemma facing clinicians, therefore, is to identify those patients with active disease, and in whom continued and/or increased treatment is necessary. This is particularly true for patients with complement-mediated diseases (e.g. aHUS) as the treatment is very expensive and the genetic risk of diseases is life-long. Currently, most patients with these diseases are treated with a “one size fits all” approach. Clinical biomarkers of disease risk and disease activity are central to the development of a personalized approach to the treatment of these diseases.
Current Focus: Complement Related Kidney Disease
The complement system contributes to renal injury in a variety of different diseases, including most forms of glomerulonephritis, many types of nephrotic syndrome, and antibody-mediated transplant rejection. Complement activation is particularly important in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3GN), two rare but devastating forms of kidney disease. Clinical evaluation of the complement system has become an essential part of the diagnostic workup of patients suspected of having various kidney diseases. For example, assays to detect complement activation or to identify underlying complement defects (e.g. mutations in complement proteins or autoantibodies to complement factors) provide important diagnostic information and can help guide treatment of patients with these diseases. It is particularly important to closely monitor the complement system in all patients treated with complement inhibitory drugs. The Food and Drug Administration has approved a therapeutic complement inhibitor (eculizumab) for the treatment of aHUS, and additional complement inhibitory drugs will likely be approved for use in other renal diseases.
The Clinical Rheumatology Laboratory subsection maintains the highly manual but also highly informative manual IFA testing. We have made the commitment to do the work and training to keep the manual reading of slides running with consistency and high quality. Please see the link below to see more on how we combine this manual testing with ELISA and unique checks and balances.