TY - JOUR
T1 - A Family Affair: Addressing the Challenges of Factor H and the Related Proteins
AU - Poppelaars, Felix
AU - Goicoechea de Jorge, Elena
AU - Jongerius, Ilse
AU - Baeumner, Antje J.
AU - Steiner, Mark-Steven
AU - Józsi, Mihály
AU - Toonen, Erik J. M.
AU - the SciFiMed consortium
AU - Pauly, Diana
N1 - Funding Information: This review was written on behalf of the SciFiMed Consortium. This is a European collaboration that is formed to create a comprehensive analytical system for the quantitative and functional assessment of the entire Factor H protein family. Principal investigators are (in alphabetical order): AB (Institute of Analytical Chemistry, Chemo-and Biosensors, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany), EG (Department of Immunology, Faculty of Medicine, Complutense University and Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain), IJ (Department of Immunopathology, Sanquin Research and Landsteiner Laboratory of the Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands & Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children?s Hospital, Amsterdam University Medical Centre, Amsterdam, Netherlands), MJ (MTA-ELTE Complement Research Group, Department of Immunology, ELTE E?tv?s Lor?nd University, Budapest, Hungary), DP (Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany & Experimental Ophthalmology, University Marburg, Marburg, Germany), FP (Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands), M-SS (Microcoat Biotechnologie GmbH, Bernried am Starnberger See, Germany), ET (R&D department, Hycult Biotech, Uden, The Netherlands). Publisher Copyright: © Copyright © 2021 Poppelaars, Goicoechea de Jorge, Jongerius, Baeumner, Steiner, Józsi, Toonen, Pauly and the SciFiMed consortium.
PY - 2021/3/30
Y1 - 2021/3/30
N2 - Inflammation is a common denominator of diseases. The complement system, an intrinsic part of the innate immune system, is a key driver of inflammation in numerous disorders. Recently, a family of proteins has been suggested to be of vital importance in conditions characterized by complement dysregulation: the human Factor H (FH) family. This group of proteins consists of FH, Factor H-like protein 1 and five Factor H-related proteins. The FH family has been linked to infectious, vascular, eye, kidney and autoimmune diseases. In contrast to FH, the functions of the other highly homologous proteins are largely unknown and, hence, their role in the different disease-specific pathogenic mechanisms remains elusive. In this perspective review, we address the major challenges ahead in this emerging area, including 1) the controversies about the functional roles of the FH protein family, 2) the discrepancies in quantification of the FH protein family, 3) the unmet needs for validated tools and 4) limitations of animal models. Next, we also discuss the opportunities that exist for the immunology community. A strong multidisciplinary approach is required to solve these obstacles and is only possible through interdisciplinary collaboration between biologists, chemists, geneticists and physicians. We position this review in light of our own perspective, as principal investigators of the SciFiMed Consortium, a consortium aiming to create a comprehensive analytical system for the quantitative and functional assessment of the entire FH protein family.
AB - Inflammation is a common denominator of diseases. The complement system, an intrinsic part of the innate immune system, is a key driver of inflammation in numerous disorders. Recently, a family of proteins has been suggested to be of vital importance in conditions characterized by complement dysregulation: the human Factor H (FH) family. This group of proteins consists of FH, Factor H-like protein 1 and five Factor H-related proteins. The FH family has been linked to infectious, vascular, eye, kidney and autoimmune diseases. In contrast to FH, the functions of the other highly homologous proteins are largely unknown and, hence, their role in the different disease-specific pathogenic mechanisms remains elusive. In this perspective review, we address the major challenges ahead in this emerging area, including 1) the controversies about the functional roles of the FH protein family, 2) the discrepancies in quantification of the FH protein family, 3) the unmet needs for validated tools and 4) limitations of animal models. Next, we also discuss the opportunities that exist for the immunology community. A strong multidisciplinary approach is required to solve these obstacles and is only possible through interdisciplinary collaboration between biologists, chemists, geneticists and physicians. We position this review in light of our own perspective, as principal investigators of the SciFiMed Consortium, a consortium aiming to create a comprehensive analytical system for the quantitative and functional assessment of the entire FH protein family.
KW - challenges - development directions
KW - complement system
KW - factor H (FH)
KW - factor H-like protein 1
KW - factor H-related protein
UR - http://www.scopus.com/inward/record.url?scp=85104207657&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2021.660194
DO - https://doi.org/10.3389/fimmu.2021.660194
M3 - Review article
C2 - 33868311
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 660194
ER -