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The Scientific World Journal
Volume 2013, Article ID 516516, 11 pages
http://dx.doi.org/10.1155/2013/516516
Research Article

Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome

1The Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
2Antibody and Hybridoma Core Facility, Taipei Medical University, Taipei 110, Taiwan
3National Research Institute of Chinese Medicine, Taipei 110, Taiwan
4Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
5Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
6Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei 104, Taiwan
7Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei 112, Taiwan
8Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County 356, Taiwan
9School of Medical Laboratory Sciences and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan
10Department of Laboratory Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan

Received 29 August 2013; Accepted 16 October 2013

Academic Editors: A. La Cava and Y. Muro

Copyright © 2013 Yu-Ching Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren’s syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about  M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren’s syndrome and may play an important role in the pathogenesis of this autoimmune disease.