Parawee SuwannalaiKarin BritsemmerRachel KnevelHans Ulrich SchererE. W.Nivine LevarhtAnnette H. Van Der Helm-Van MilDirkjan Van SchaardenburgTom W.J. HuizingaRené E.M. ToesL. A. TrouwLeiden University Medical Center - LUMCMahidol UniversityJan Van Breemen Research Institute2018-11-092018-11-092014-01-01Annals of the Rheumatic Diseases. Vol.73, No.1 (2014), 270-27614682060000349672-s2.0-84889635694https://repository.li.mahidol.ac.th/handle/20.500.14594/33468Objectives Anticitrullinated protein antibodies (ACPA) are specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Previously we have shown that ACPA display a considerably lower avidity as compared with antibodies against recall antigens. Nonetheless, ACPA-avidity did vary between patients. As antibody mediated effects are influenced by antibodyavidity, we now investigated ACPA-avidity in relation to biological activity and clinical outcome. Methods We determined the avidity of ACPA and related this with severity of joint damage in two Dutch early-RA cohorts containing 199 and 132 patients respectively. Differences in effector functions of low- and high-avidity ACPA were studied. Results Extensive variation in ACPA-avidity between patients was observed. This allowed the analysis of the relationship between avidity and severity. The presence of low-avidity ACPA is associated with a higher rate of joint destruction. This finding was replicated in an independent cohort. Analysis of the properties of lowversus high-avidity ACPA revealed that low-avidity ACPA are less hampered in their ability to bind 'new' citrullinated antigens. Although no differences could be observed regarding cellular activation via Fc-γ receptors, low-avidity ACPA were more potent in activating the complement system. Conclusions Patients with low-avidity ACPA display a higher rate of joint destruction. Low-avidity ACPA display a higher potency to interact with more citrullinated antigens in time and show that low-avidity ACPA are more potent in complement activation. These data indicate that (low) avidity impacts on the biological activity of ACPA and associates with a worse radiological outcome.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineArticleSCOPUS10.1136/annrheumdis-2012-202615