On April9, 2014, researchers at Xiaoming Gao’s group published an article entitled “Disease Association and Arthritogenic Potential of Circulating Antibodies against the a1,4-Polygalacturonic Acid Moiety” in Journal of Immunology.
Much progress has been made in recent years on the diagnostic value, Ag speci?city, and pathogenic roles of autoantibodies correlated to the development of rheumatoid arthritis (RA) in humans. However,carbohydrate Ag-speci?c autoantibodies that may also play important roles in RAhave largely been ignored. In this article, we report that serum levels of Abscapable of recognizing a1,4-polygalacturonic acid [(PGA); major structural component of pectin] strongly correlate with RA in humans. The measurements of PGA-speci?c Abs (PGA-Abs) in sera are comparable to rheumatoid factors and anti–cyclic citrullinated peptide Abs as serological diagnostic markers for RA in terms of sensitivity and speci?city. Immunohistochemical staining results indicate that the PGA-Abs selectively bound synovial membrane cells and chondrocytes in the joints of both humans and rabbits (but not rodents). Induction of PGA-Abs by s.c. immunization of rabbits with carrier protein–conjugated synthetic PGA led to severe in?ammatory reactions (synovial hyperplasia, small vessel proliferation, and in?ammatory cell in?ltration) in the joints. Injection of af?nity puri?ed anti-PGA IgG into the synovial cavityof rabbits resulted in accumulation of proin?ammatory cytokines such as TNF-a,IL-8, and IL-1b in synovial ?uid, as well as local pathological damage. We conclude that the PGA–cross-reactive moiety represents a major autoantigen in the joints and can be targeted by autoantibodies capable of triggering arthritogenic responses in vivo.
Hui Dai is the first author of the paper. Contributing author are Hong-Liang Dong, Fang-Yuan Gong, Shu-Liang Sun, Xiang-Yuan Liu, Zhan-GuoLi and Si-Dong Xiong. Prof. Xiaoming Gao is the corresponding author of the paper. This work was supported by grants from National Key Basic Research Programs (2010CB529102), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1075), the Natural Science Foundation of China (31370908/31070781/81102253), and the Doctoral Program of Higher Education (20100001120042).