Anti Citrullinated Protein Antibodies From Synovial Fluid of Rheumatoid Arthritis Patients Enhance Osteoclastogenesis

Akilan Krishnamurthy¹, Nancy Vivar Pomiano², Catia Cerqueira³, Elena Ossipova³, Karin Lundberg⁴, Ulrike Harre⁵, Vivianne Malmström⁶, Per Johan Jakobsson⁷, Lars Klareskog⁸, Georg Schett⁹ and Anca Catrina³, ¹Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ²Rheumatology unit, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, ³Department of Medicine, Rheumatology unit, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, ⁴Rheumatology unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁵Institute for Clinical Immunology, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁶Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, ⁷Rheumatology unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁸Department of Medicine, Rheumatology Unit, Karolinska Institute, Stockholm, Sweden, ⁹Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: anti-CCP antibodies, anti-citrullinated protein/peptide antibodies (ACPA), Bone metabolism and rheumatoid arthritis (RA)

Session Information

Title: Biology and Pathology of Bone and Joint

Session Type: Abstract Submissions (ACR)

Background/Purpose: Presence of anti CCP2 antibodies identifies a subgroup of RA patients that are more prone to develop bone erosions. We hypothesized that anti CCP2 IgG might have a direct effect on bone, and thus investigated the effect of anti CCP2 IgG isolated from synovial fluid (SF) of RA patients on osteoclastogenesis and bone destruction in an in vitro system.

Methods: SF (n=26) samples were collected from RA patients with anti-CCP2 IgG levels above 300AU/ml. Total IgG was isolated on Protein G columns, before applied to CCP2 affinity columns, kindly donated by EuroDiagnostica. A pool of the purified anti-CCP IgG fractions, as well as a pool of the corresponding column flow through IgG fractions were tested for the ability to influence osteoclastogenesis and bone destruction. CD14 positive cells isolated by positive selection from peripheral blood of healthy individuals were cultured in the presence of GM-CSF and IL-4 to generate immature dendritic cells. After 6 days of culture, cells were incubated in the presence of RANKL and M-CSF, with or without CCP2 IgG or flow through IgG (at a final concentration of 100ng/ml) for an additional 12 days. Osteoclasts formation was evaluated as total number of multinucleated TRAP positive cells. In parallel cultures were grown on osteologic discs and % of resorbed out of total disc areas were evaluated by computer assisted image analyses

Results: The CCP2 IgG pool significantly increased the formation of osteoclasts. In contrast the pool of the flow through IgG did not stimulate RANKL-driven osteoclastogenesis from immature dendritic cells. When assessing bone destruction CCP2 IgG but not flow through IgG was able to increase the percentage of synthetic bone resorption areas.

Conclusion: Here, we demonstrate that ACPA IgG, isolated from synovial fluid of RA patients, have the ability to enhance the RANKL-driven osteocalstogenesis from immature dendritic cells. Our findings suggest that ACPA might have a direct pathogenic effect in RA associated bone destruction.

Disclosure:

A. Krishnamurthy,
None;

N. Vivar Pomiano,
None;

C. Cerqueira,
None;

E. Ossipova,
None;

K. Lundberg,
None;

U. Harre,
None;

V. Malmström,
None;

P. J. Jakobsson,
None;

L. Klareskog,
None;

G. Schett,
None;

A. Catrina,
None.

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-citrullinated-protein-antibodies-from-synovial-fluid-of-rheumatoid-arthritis-patients-enhance-osteoclastogenesis/