Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome
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 inf...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/516516 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832555326174396416 |
|---|---|
| author | Yu-Ching Lee Keng-Chang Tsai Sy-Jye Leu Tuan-Jen Wang Chia-Yu Liu Yi-Yuan Yang |
| author_facet | Yu-Ching Lee Keng-Chang Tsai Sy-Jye Leu Tuan-Jen Wang Chia-Yu Liu Yi-Yuan Yang |
| author_sort | Yu-Ching Lee |
| collection | DOAJ |
| description | 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 6×10-8 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. |
| format | Article |
| id | doaj-art-009de526884f4776a38d280f718d6725 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-009de526884f4776a38d280f718d67252025-02-03T05:48:29ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/516516516516Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s SyndromeYu-Ching Lee0Keng-Chang Tsai1Sy-Jye Leu2Tuan-Jen Wang3Chia-Yu Liu4Yi-Yuan Yang5The Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, TaiwanNational Research Institute of Chinese Medicine, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, TaiwanDepartment of Laboratory Medicine, Mackay Memorial Hospital, Taipei 104, TaiwanDepartment of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei 112, TaiwanAntibody and Hybridoma Core Facility, Taipei Medical University, Taipei 110, TaiwanWe 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 6×10-8 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.http://dx.doi.org/10.1155/2013/516516 |
| spellingShingle | Yu-Ching Lee Keng-Chang Tsai Sy-Jye Leu Tuan-Jen Wang Chia-Yu Liu Yi-Yuan Yang Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome The Scientific World Journal |
| title | Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome |
| title_full | Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome |
| title_fullStr | Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome |
| title_full_unstemmed | Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome |
| title_short | Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome |
| title_sort | isolation characterization and molecular modeling of a rheumatoid factor from a hepatitis c virus infected patient with sjogren s syndrome |
| url | http://dx.doi.org/10.1155/2013/516516 |
| work_keys_str_mv | AT yuchinglee isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome AT kengchangtsai isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome AT syjyeleu isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome AT tuanjenwang isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome AT chiayuliu isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome AT yiyuanyang isolationcharacterizationandmolecularmodelingofarheumatoidfactorfromahepatitiscvirusinfectedpatientwithsjogrenssyndrome |