Autoimmunity to citrullinated type II collagen in rheumatoid arthritis

The production of autoantibodies to citrullinated type II collagen and the citrullination of type II collagen were analyzed in rheumatoid arthritis. Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum samples from 130 rheumatoid arthritis patients. Autoantibodies to native noncitrullinated type II collagen were detected in 14.6% of serum samples, all of which were positive for anti-citrullinated type II collagen antibodies. Serum samples were also positive for anti-citrullinated type II collagen antibodies in 1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis patients, and 18 psoriatic arthritis patients were all negative for anti-citrullinated type II collagen antibodies. Anti-citrullinated type II collagen antibodies and fragments of citrullinated type II collagen were found in the synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis patients. Moreover, anti-citrullinated type II collagen antibodies were isolated from the synovium of affected knee joints in 8 rheumatoid arthritis patients using antigen/antibody immunocomplex dissociation buffer but not by using standard buffers. These findings indicate that autoantibodies that react with citrullinated type II collagen are specifically produced and that immunocomplexes composed of fragments of citrullinated type II collagen and autoantibodies are deposited in the inflamed articular synovium in rheumatoid arthritis patients. Assaying for the presence of anti-citrullinated type II collagen antibodies may therefore be useful for diagnosing rheumatoid arthritis, and the deposition of these immunocomplexes in the articular synovium may be involved in pathogenesis

Autocitrullination confers monocyte chemotactic properties to peptidylarginine deiminase 4

Abstract Peptidylarginine deiminase 4 (PAD4) contributes to the production of citrullinated proteins as autoantigens for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). PAD4 can also self-deiminate via autocitrullination. However, the role of this process in RA pathogenesis has not been elucidated. This study aimed to clarify PAD4 function before and after autocitrullination and identify citrullinated PAD4 in the synovial fluid of patients with RA. The autocitrullination of recombinant human PAD4 (rhPAD4) was catalyzed in vitro and determined using anti-modified citrulline immunoblotting. Monocyte chemotaxis was evaluated using Boyden chambers, and citrullinated rhPAD4’s ability to induce arthritis was assessed in a C57BL/6J mouse model. Citrullinated PAD4 levels were measured in the synovial fluid of patients with RA and osteoarthritis using a novel enzyme-linked immunosorbent assay. Chemotactic findings showed that citrullinated rhPAD4 recruited monocytes in vitro, whereas unmodified rhPAD4 did not. Compared to unmodified rhPAD4, citrullinated rhPAD4 induced greater inflammation in mouse joints through monocyte migration. More citrullinated PAD4 was found in the synovial fluid of patients with RA than in those with osteoarthritis. Citrullinated PAD4 was even detected in ACPA-negative patients with RA. The autocitrullination of PAD4 amplified inflammatory arthritis through monocyte recruitment, suggesting an ACPA-independent role of PAD4 in RA pathogenesis

Positioning the femoral bone socket and the tibial bone tunnel using a rectangular retro-dilator in anterior cruciate ligament reconstruction.

PurposeThe purpose of this study was to evaluate the positions of femoral bone sockets and tibial bone tunnels made with the rectangular retro-dilator (RRD), which we manufactured for anterior cruciate ligament reconstruction (ACLR) with a bone-patella tendon-bone (BPTB) graft which is fixed into the rectangular bone socket and tunnel made at anatomical ACL insertion sites.Methods42 patients who had undergone ACLR with BPTB using the RRD were evaluated to assess bone socket and tunnel positions by the quadrant method and Magnussen classification using three-dimensional (3-D) CT. Intra-operative complications were also investigated in all patients.Results3-D CT of the operated knee joints using the RRD showed that the bone socket and tunnel were placed in anatomical positions. In the quadrant method, the mean position of the femoral bone socket aperture was located at 22.0 ± 4.2% along the Blumensaat's line, and 37.4 ± 7.2% across the posterior condylar rim. The mean positions of the tibial bone tunnel aperture were 37.7 ± 5.2% and 46.1 ± 2.2% antero-posteriorly and medio-laterally, respectively. In addition, according to the Magnussen classification, 39 cases were evaluated as type 1, and almost all were located behind the lateral intercondylar ridge (also known as the resident's ridge). 3 cases were classified as type 2, which overlapped with the resident's ridge. A partial fracture of BPTB bone fragment was observed in 2 patients, but no serious complications including neurovascular injury were observed.ConclusionThe study indicates that the use of RRD achieves a safe anatomical reconstruction of the ACL

Anterior Cruciate Ligament Reconstruction With Bone–Patellar Tendon–Bone Graft Through a Rectangular Bone Tunnel Made With a Rectangular Retro-dilator: An Operative Technique

Good clinical results have been reported with anatomic anterior cruciate ligament (ACL) reconstructions in which rectangular bone–patellar tendon–bone (BTB) grafts were fixed into rectangular bone tunnels made at anatomic ACL insertion sites of the femur and tibia (anatomic rectangular tunnel BTB ACL reconstruction). Notwithstanding these good results, some problems have remained unsolved, including procedural complexity and risk of damage to the femoral posterior tunnel wall, damage to nerves and blood vessels, and damage to cartilage. The purpose of this report is to present our technique of ACL reconstruction with BTB graft through a rectangular bone tunnel made with a rectangular retro-dilator. Our procedure may become a safe option for anatomic rectangular tunnel BTB ACL reconstruction because of the following advantages: (1) bone tunnels can be created more safely and accurately than in methods using transtibial and far medial portals, (2) the bone tunnel preparation procedure is less invasive than the standard outside-in method, (3) technical failure–related risks are lower because the guidewire is inserted only once, and (4) the operation time is shorter because the method is a single-bundle procedure