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 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.
Highlights
Sjogren’s syndrome (SS) is an autoimmune disorder that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes due to functional impairment of the salivary and lachrymal glands [1]
The results showed that more than 90% of the clones contain a fragment of 750 bp in plasmid DNA after second around panning, indicating that the panning eliminated most of the phage clones not displaying Fab fragments on their surfaces, which accounted for less than 10% of phage clones in the original antibody library we constructed
We described the isolation and characterization of RFL11 Fab directed against human IgG Fc from a patient with Sjogren’s syndrome and HCV infection
Summary
Sjogren’s syndrome (SS) is an autoimmune disorder that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes due to functional impairment of the salivary and lachrymal glands [1]. SS occurs in a primary form not associated with other diseases and in a secondary form that complicates other rheumatic conditions, with the most common being rheumatoid arthritis. Many rheumatologic manifestations associated with chronic HCV infection include arthralgia, myalgia, arthritis, vasculitis, and sicca syndrome [6]. Clinical studies suggest the possibility of a close relationship among SS, HCV, and B-cell lymphoproliferative disorders [2, 4]. This triple association suggests an important role of associated autoimmune and/or chronic viral diseases in the pathogenesis of B-cell lymphoproliferative disorders and reinforces the hypothesis of a link among autoimmunity, infection, and cancer [4]
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