Some antibodies play ‘back-up defense’ against kidney disease in mice
Immune system researchers have long known that some antibodies are highly capable of identifying and disabling foreign substances inside the body -- called antigens –by clumping them together and removing them from the body by activating complement and binding to antibody surface receptors, called FcgRs, on cells.
In a Nov. 2, 2014 study published online in Nature by Richard Strait, MD, et al., researchers have discovered that certain types of antibodies – even though they do not activate, complement or interact strongly with activating antibody receptors – still play critical roles in clearing these antigens from the body and preventing disease.
Strait’s study, co-published with several other investigators including senior author and his mentor, Fred Finkelman, MD, Division of Immunobiology, looked specifically at kidney disease associated with the interaction of antibodies with antigen in mice. In normal healthy mice, antigen exposure did not cause disease. However, in mice genetically deficient in IgG1, the most abundant subtype of antibody and roughly equivalent to human IgG4, antigen exposure resulted in developing a fatal kidney disease.
The fatal kidney disease arose secondary to the occurrence of large and numerous cryoglobulin complexes made from the interaction between the antigen and the antibody subtype IgG3. These complexes proceeded to obstruct blood flow to the kidney, eventually causing organ failure and death.
Cryoglobulins also are responsible for kidney damage and other tissue injury in hepatitis C and other diseases. Providing IgG1 back to IgG1-deficient mice prevented cryoglobulin development and saved the mice. Of extreme interest is that the IgG1 performed this disease prevention independent of the usual involvement of the complement system and the antibody receptors.
This study demonstrates how important various characteristics of each subtype of antibody can be in disease development or prevention, Strait says. These findings could have implications for other human conditions linked to antibodies, including myasthenia gravis and some skin diseases.
