Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of... Show moreIntervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases. Show less
Ioan-Facsinay, A.; Bannoudi, H. el; Scherer, H.U.; Woude, D. van der; Menard, H.A.; Lora, M.; ... ; Toes, R.E.M. 2010
OBJECTIVE:: Anti-citrullinated protein antibodies (ACPA) exhibit unique specificity for RA. Whether and how ACPA contribute to disease pathogenesis, however, is incompletely understood. The Fc part... Show moreOBJECTIVE:: Anti-citrullinated protein antibodies (ACPA) exhibit unique specificity for RA. Whether and how ACPA contribute to disease pathogenesis, however, is incompletely understood. The Fc part of human IgG carries two N-linked glycan moieties which are crucial for the structural stability of the antibody and modulate its binding affinity to Fcgamma receptors and its ability to activate complement. We have purified ACPA from serum and synovial fluid and analyzed Fc glycosylation profiles in a specific manner. METHODS:: ACPA were isolated by affinity purification using cyclic citrullinated peptides as antigen. IgG(1) Fc glycosylation was analyzed by mass spectrometry. ACPA glycan profiles were compared to glycan profiles of total serum IgG(1) obtained from 85 well-characterised patients. Glycan profiles of paired synovial fluid and serum samples were available from 11 additional patients. RESULTS:: Compared to the pool of serum IgG(1), ACPA IgG(1) lack terminal sialic acid residues. In synovial fluid, ACPA are highly agalactosylated and lack sialic acid residues, a feature that was not detected for total synovial fluid IgG(1). Moreover, differential ACPA glycan profiles were detected in RF-positive versus -negative patients. CONCLUSION:: ACPA IgG(1) exhibit a specific Fc-linked glycan profile which is distinct from total serum IgG(1). Moreover, Fc glycosylation of ACPA differs markedly between synovial fluid and serum. As Fc glycosylation directly affects the recruitment of Fc-mediated effector mechanisms, these data could further our understanding of the contribution of ACPA to disease pathogenesis. Show less
