Abstract
BackgroundGenetic studies have pointed out that CD226 variants, encoding DNAM-1, could be associated with susceptibility to rheumatoid arthritis. Therefore, we aimed to determine the influence of DNAM-1 on the development of arthritis using the collagen-induced arthritis (CIA) mouse model.MethodsCIA was induced in mice on a DBA/1 background, treated in parallel with a DNAM-1 neutralizing monoclonal antibody, a control IgG and PBS, respectively. CIA was also induced in mice deficient for DNAM-1(dnam1−/−) and control dnam-1+/+ mice on a C57/BL6 background. Mice were monitored for clinical and ultrasound signs of arthritis. Histological analysis was performed to search for inflammatory infiltrates and erosions. The Mann–Whitney U test for non-related samples was used for statistical analysis.ResultsThere was a non-significant trend for a less arthritic phenotype in mice receiving anti-DNAM-1 mAb at both clinical, ultrasound and histological assessments. But, we did not observe any difference between dnam1+/+ and dnam1−/− mice for incidence nor severity of clinical arthritis. Histological analysis revealed inflammatory scores similar in both groups, without evidence of erosion. Collagen antibodies levels were similar in all mice, confirming immunization with collagen.ConclusionDespite some clues suggesting a role of DNAM-1 in arthritis, these complementary approaches demonstrate no contribution of CD226/DNAM-1 in the arthritic phenotype. These results contrast with previous studies showing a role in vivo of DNAM-1 in some autoimmune disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0056-5) contains supplementary material, which is available to authorized users.
Highlights
Genetic studies have pointed out that CD226 variants, encoding DNAX accessory molecule 1 (DNAM-1), could be associated with susceptibility to rheumatoid arthritis
Anti-DNAM-1 monoclonal antibody (mAb) does not protect from the development of collagen-induced arthritis (CIA) The mouse model of CIA was used to evaluate the antiarthritic potential of DNAM-1 inhibition in vivo using a neutralizing anti-DNAM-1 mAb
Clinical evidence of arthritis was observed in 5/7 (71%) mice treated with anti-DNAM-1 mAb, 6/7 (86%) mice treated with control IgG and 7/7 (100%) mice injected with PBS (p = 0.51 and 0.13) (Figure 1a)
Summary
Genetic studies have pointed out that CD226 variants, encoding DNAM-1, could be associated with susceptibility to rheumatoid arthritis. Rheumatoid arthritis (RA) is a frequent disease leading to joint destruction, deformity, and disability. Biologics have shown their efficacy in limiting joint destruction and have dramatically improved the outcome of RApatients. The pathogenesis of RA is characterized by chronic inflammation and synovial infiltration of immune cells [4,5]. It results from the combination of genetic susceptibility genes and environmental factors [6]. The majority of these genetic factors was associated with other autoimmune diseases, which were not characterized by an arthritic phenotype, underlining the concept of a shared genetic background between autoimmune diseases [8,9,10]
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