Identification of Natural Bispecific Antibodies against Cyclic Citrullinated Peptide and Immunoglobulin G in Rheumatoid ArthritisReport as inadecuate




Identification of Natural Bispecific Antibodies against Cyclic Citrullinated Peptide and Immunoglobulin G in Rheumatoid Arthritis - Download this document for free, or read online. Document in PDF available to download.

Background

Previous studies indicate that natural bispecific antibodies can be readily produced in vivo when the body is simultaneously stimulated with 2 distinct antigens. Patients with rheumatoid arthritis RA usually exhibit persistent immune responses to various autoantigens, raising the possibility that natural bispecific antibodies against 2 distinct autoantigens might exist.

Methodology-Principal Findings

We identified the presence of natural bispecific antibodies against cyclic citrullinated peptide CCP and immunoglobulin G IgG in RA patients- sera by means of a double-antigen sandwich enzyme-linked immunosorbent assay ELISA. The spontaneous emergence of bispecific antibodies was confirmed by mixing different proportions of 1 anti-CCP-positive serum and 1 rheumatoid factor RF-positive serum in vitro. Among the tested samples, positive correlations were found between the presence of bispecific antibodies and both IgG4 anti-CCP antibodies and IgG4 RF r = 0.507, p<0.001 and r = 0.249, p = 0.044, respectively, suggesting that the IgG4 subclass is associated with this phenomenon. Furthermore, bispecific antibodies were selectively generated when several anti-CCP- and RF-positive sera were mixed pairwise, indicating that factors other than the monospecific antibody titers may also contribute to the production of the natural bispecific antibodies.

Conclusions-Significance

We successfully identified the presence of natural bispecific antibodies. Our results suggest that these antibodies originate from anti-CCP and RF in the sera of RA patients. The natural occurrence of bispecific antibodies in human diseases may provide new insights for a better understanding of the diseases. Further investigations are needed to elucidate their precise generation mechanisms and explore their clinical significance in disease development and progression in a larger study population.



Author: Wei Wang, Jinming Li

Source: http://plos.srce.hr/



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