Assistant Professor of Medicine Anuja Java, MD, Division of Nephrology, recently attended the 27th International Complement Society meeting held in Santa Fe, New Mexico, to present her work titled, A comprehensive analysis of complement factor I variants in atypical hemolytic uremic syndrome (aHUS).
The largest and oldest complement conference hosts researchers, physicians, clinicians and others familiar with the discipline, as well as individuals from other medical fields who want to learn more about complement immunology. The meeting covers all areas of complement immunology, from basic research to clinical studies to complement therapeutics.
The complement system, consisting of more than 30 proteins, enhances (i.e. complements) the ability of antibodies and phagocytic cells to eliminate infectious microorganisms. aHUS is a devastating disease that primarily affects kidney function by causing abnormal blood clots to form in the small blood vessels of the kidney. The disease occurs secondary to an abnormal regulation and, thus, overactivity of the alternative pathway of the complement system. Kidney failure resulting from aHUS leads to end-stage renal disease in about half of all cases.
Approximately 60% of patients with aHUS carry a rare genetic variant in one of the complement system proteins. However, most of these variants have not been functionally characterized and are reported as “variants of uncertain significance (VUS).” The presence of VUS is a major obstacle in the management of aHUS.
“In our work, we have conducted an in-depth functional characterization and structural modeling of complement Factor I (FI) variants in five patients with aHUS,” says Dr. Java. “These analyses allowed us to definitively categorize the FI variants into pathogenic or benign. Based upon these evaluations, we were able to develop an individualized treatment plan for each patient.”
Dr. Java has been investigating the role of complement receptors and regulators in the pathogenesis of immune and inflammatory processes in the kidney in collaboration with John Atkinson, MD, Chief – Division of Rheumatology, the Samuel B. Grant Professor of Medicine, and Professor of Molecular Microbiology at WU.
“John Atkinson is the guru of complement,” says Java. “Labs from around the world (England, Italy, Spain, etc.) reach out to him with questions and issues related to their complement work. I feel extremely fortunate to have trained under him as my mentor and thoroughly enjoy working with him now as a collaborator.”
Authors of the abstract presented by Dr. Java at the complement conference include Anuja Java, Nicola Pozzi, Zheng Hu, Zhen Ren, Paula Bertram, Laura Cline, and John Atkinson.
Related to Dr. Java’s work, David Kavanagh, MD, will talk about aHUS at next week’s Renal Research Conference (Nov. 13, Noon-1 p.m.). He is Professor of Complement Therapeutics at the National Renal Complement Therapeutics Centre in England. Dr. Kavanagh is a WU alum and is visiting the campus to speak and meet with Nephrology faculty.