Complement in physiology and pathology

Complement is a powerful innate immune surveillance system in blood and in tissues. It protects the host from pathogens, but can induce host tissue damage and chronic inflammation when overactivated. With the advent of complement therapeutics, it is critical to decipher whether and how complement contributes to the disease process.

Main projects developed in this theme

Complement in C3 glomerulopathies and atypical hemolytic uremic syndrome:

Thanks to our cohorts, among the largest cohorts in the world, we study the molecular mechanisms of complement overactivation and tissue injury in these prototypical complement-mediated kidney diseases. We discovered the mechanisms of action of novel auto-antibodies and genetic abnormalities in these diseases. Our work has a major societal impact, thanks to transfer to diagnostics and patients’ management, through the Complement diagnostics laboratory of Dr. Fremeaux-Bacchi in HEGP hospital and the collaborating clinicians. (PI: Dr. Veronique Fremaux-Bacchi/Sophie Chauvet)

– Complement in monoclonal gammopathies and kidney diseases:

We discovered that the monoclonal immunoglobulin from patients with this condition is able to enhance complement alternative pathway overactivationindependently of its antigenic specificity. We study how the biochemical properties of either polyclonal or monoclonal immunoglobulin in these patients modulate the balance of C3/C5 convertase activity; how it influences the intra renal immune cell infiltration and blood immune response and how this correlates with renal prognosis. (PI: Dr. Sophie Chauvet/Véronique Frémeaux Bacchi)

– Complement and autoimmune diseases:

The link between the complement system and autoimmunity is of critical importance. On one side different auto-antibodies targeting the complement system have been discovered and characterized by our group in different kinds of diseases (atypical hemolytic uremic syndrome, C3 glomerulopathies, autoimmune myopathies), and on the other side, we study some diseases in which the complement system acts as the armed wing of the autoantibodies (such as anti-phospholipids syndrome, APLS). The research is performed in a close continuity with the laboratory of Immunology of the Georges Pompidou hospital (PI: Mare Agnes Dragon-Durey).

Complement in diseases with heme overload:

We discovered that heme, when released from hemoglobin or myoglobin during hemolysis or muscle injury, binds to C3 and activates complement. We demonstrated the pathological role of the heme-mediated complement activation in the disease process of atypical hemolytic uremic syndrome, sickle cell disease and rhabdomyolysis-induced acute kidney injury. We are testing heme scavengers and complement inhibitors as therapeutic strategies for these diseases. (PI: Dr. Lubka Roumenina)

– Complement and cancer:

Complement is a major, previously underestimated, modulator of cells behavior. We study complement as a modulator of the tumor cell fate and tumor microenvironment and its actions within the complement cascade as well as its non-canonical functions. Gained fundamental knowledge will allow us to search for novel prognostic markers in patients’ cohorts with renal and lung cancers. (PI: Dr. Lubka Roumenina)

Permanent members

Dr. Lubka T. Roumenina, CRCN INSERM

Dr. Sophie Chauvet, MCU-PH nephrologist, European George Pompidou Hospital

Dr. Marie Agnes Dragon-Durey, MCU-PH biologist, European George Pompidou Hospital

Dr. Veronoque Fremeaux-Bacchi, PH biologist, European George Pompidou Hospital

Mrs Tania Robe-Rybkine, study engineer, Sorbonne Université