Search

Much progress has been made in recent years on the diagnostic value, Ag specificity, and pathogenic roles of autoantibodies correlated to the development of rheumatoid arthritis (RA) in humans. However, carbohydrate Ag-specific autoantibodies that may also play important roles in RA have largely been ignored. In this article, we report that serum levels of Abs capable of recognizing α1,4-polygalacturonic acid [(PGA); major structural component of pectin] strongly correlate with RA in humans. The measurements of PGA-specific 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 specificity. 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 inflammatory reactions (synovial hyperplasia, small vessel proliferation, and inflammatory cell infiltration) in the joints. Injection of affinity purified anti-PGA IgG into the synovial cavity of rabbits resulted in accumulation of proinflammatory cytokines such as TNF-α, IL-8, and IL-1β in synovial fluid, 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. [ABSTRACT FROM AUTHOR]

Exposure to pathogen-associated molecular patterns (PAMPs) by vaccination or infection is known to have beneficial effects on neoplastic diseases, although the underlying molecular mechanisms are so far unclear. In this article, we report that Abs against (l→6)-β-D-glucan, a typical microbial PAMP and a major target for high titer circulating natural Abs in healthy human subjects, cross-recognize a novel tumor-associated carbohydrate Ag on cancer cells. The (l→6)-β-glucan cross-reactive moiety is immunologically dominant in tumor cells, as C57BL/6 mice harboring EL-4 solid tumors produced anti-(1→6)-β-glucan Abs and the titer of which significantly correlated with enhanced survival and smaller tumor burden. Moreover, the (1→6)-β-glucan-specific Abs exhibited potent tumoricidal activities in vitro. C57BL/6 mice immunized with Candida albicans produced protective immunity against inoculated EL-4 tumors, which was attributed to the formation of (1→6)-β-glucan-specific Abs. Importantly, (l剂6)-β-glucan-specific Abs significantly prolonged the survival and reduced the tumor size in mice inoculated with EL-4 tumors. Our results demonstrate that the (1→6)-β-glucan cross-reactive moiety represents a focal point between infection immunity and cancer surveillance, and natural Abs against this epitope may contribute to the first-line antitumor surveillance in humans. Our data also provide important explanation for the long-observed relationship between feverish infection and concurrent remission from cancer. [ABSTRACT FROM AUTHOR]