Higher Expression of Latency-Associated Peptide on the Surface of Peripheral Blood Monocytes in Patients with Rheumatoid Arthritis may be Protective Against Articular Erosions Gleb Slobodin, 1,4,5 Lisa Kaly, 2 Regina Peri, 3 Aharon Kessel, 3,4 Itzhak Rosner, 2,4 Elias Toubi, 3,4 Doron Rimar, 2,4 Nina Boulman, 2,4 Michael Rozenbaum, 2,4 and Majed Odeh 1,4 Abstract—Latency-associated peptide (LAP) forms small latent complexes with transforming gro- wth factor beta 1 (TGF-β1). TGF-β–LAP complexes can be detected on the surfaces of immune cells and have been recently shown to play a role in immune regulation through TGF-β1-mediated functions. A study was undertaken to investigate the correlation of LAP expression on the surface of immune cells and presence of articular erosions in patients with rheumatoid arthritis (RA). Venous blood was obtained from patients with severe RA as well as from healthy control subjects. Surface expression of LAP on peripheral blood mononuclear cells was analyzed by flow cytometry, meas- ured as flow cytometric intensity separately on CD14 + and CD14 - cells, and compared between RA patients and healthy subjects. Patients with RA demonstrated higher surface expression of LAP on both CD14 + and CD14 - mononuclear cells than healthy individuals. Patients with erosive RA had significantly reduced intensity of anti-LAP staining on the CD14 + cells when compared to RA patients without erosions (p 0 0.01). The intensity of anti-LAP staining on CD14 - cells was not different between groups of RA patients. Higher expression of LAP on the surface of the cells of monocyte lineage may be protective of formation of articular erosions in RA. Further studies are needed to elaborate the mechanism of this phenomenon. KEY WORDS: rheumatoid arthritis; articular erosion; latency-associated peptide; transforming growth factor beta. Latency-associated peptide (LAP) is a polypeptide, which forms a small latent complex with transforming growth factor beta 1 (TGF-β1) immedi- ately after the latter is synthesized by the producing cell. While thus complexed, TGF-β1 is inactive and cannot bind its surface receptors. Activation of TGF- β1 requires dissociation from LAP, which can be degraded extracellularly by proteases or an acidic microenvironment. TGF-β1 is a multifunctional pep- tide that controls proliferation, differentiation, and other functions in many cell types. TGF-β1 is abundant in bone tissue where it triggers bone formation by expanding the pool of committed osteoblasts and inducing the expression of Runx2. At high concentrations, it also inhibits differentiation of osteoclasts [1]. TGF-β1–LAP complexes can be detected by anti-LAP staining and measured on the surface of TGF-β1-producing cells [2, 3]. Recently, we have shown positive correlation be- tween the degree of bone formation and numbers of LAP-positive monocytes in the peripheral blood of patients with ankylosing spondylitis [4]. In this study, we tested the hypothesis that the surface expression of LAP on immune cells is higher in patients with nonerosive rheumatoid arthritis (RA) when compared to patients with erosive disease. 1 Internal Medicine A, Bnai Zion Medical Center, P.O. Box 4940, Haifa, 31048, Israel 2 Rheumatology, Bnai Zion Medical Center, Haifa, Israel 3 Immunology, Bnai Zion Medical Center, Haifa, Israel 4 Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 5 To whom correspondence should be addressed at Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. E-mail: gslobodin@yahoo.com 0360-3997/13/0000-0001/0 # 2013 Springer Science+Business Media New York Inflammation ( # 2013) DOI: 10.1007/s10753-013-9639-6