A shared epitope of collagen type XI and type II is recognized by pathogenic antibodies in mice and humans with arthritis
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12.04.2018 |
Tong D.
Lönnblom E.
Yau A.
Nandakumar K.
Liang B.
Ge C.
Viljanen J.
Li L.
Bãlan M.
Klareskog L.
Chagin A.
Gjertsson I.
Kihlberg J.
Zhao M.
Holmdahl R.
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Frontiers in Immunology |
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1 |
Ссылка
© 2018 Tong, Lönnblom, Yau, Nandakumar, Liang, Ge, Viljanen, Li, Bãlan, Klareskog, Chagin, Gjertsson, Kihlberg, Zhao and Holmdahl. Background: Collagen XI (CXI) is a heterotrimeric molecule with triple helical structure in which the a3(XI) chain is identical to the a1(II) chain of collagen II (CII), but with extensive posttranslational modifications. CXI molecules are intermingled in the cartilage collagen fibers, which are mainly composed of CII. One of the alpha chains in CXI is shared with CII and contains the immunodominant T cell epitope, but it is unclear whether there are shared B cell epitopes as the antibodies tend to recognize the triple helical structures. Methods: Mice expressing the susceptible immune response gene Aq were immunized with CII or CXI. Serum antibody responses were measured, monoclonal antibodies were isolated and analyzed for specificity to CII, CXI, and triple helical collagen peptides using bead-based multiplex immunoassays, enzyme-linked immunosorbent assays, and Western blots. Arthritogenicity of the antibodies was investigated by passive transfer experiments. Results: Immunization with CII or CXI leads to a strong T and B cell response, including a cross-reactive response to both collagen types. Immunization with CII leads to severe arthritis in mice, with a response toward CXI at the chronic stage, whereas CXI immunization induces very mild arthritis only. A series of monoclonal antibodies to CXI were isolated and of these, the L10D9 antibody bound to both CXI and CII equally strong, with a specific binding for the D3 epitope region of a3(XI) or a1(II) chain. The L10D9 antibody binds cartilage in vivo and induced severe arthritis. In contrast, the L5F3 antibody only showed weak binding and L7D8 antibody has no binding to cartilage and did not induce arthritis. The arthritogenic L10D9 antibody bound to an epitope shared with CII, the triple helical D3 epitope. Antibody levels to the shared D3 epitope were elevated in the sera from mice with arthritis as well as in rheumatoid arthritis. Conclusion: CXI is immunologically not exposed in healthy cartilage but contains T and B cell epitopes cross-reactive with CII, which could be activated in both mouse and human arthritis and could evoke an arthritogenic response.
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Rare case of orbital nodular fasciitis
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01.01.2018 |
Grusha Y.
Ismailova D.
Kochetkov P.
Fedorov A.
Dzemeshkevich V.
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Clinical and Experimental Surgery |
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0 |
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© 2018 GEOTAR Media. All rights reserved. A rare case of orbital nodular fasciitis in young female is presented. This case is of interest not only because of diagnosis but also due to localization of the mass with inferior orbital wall destruction and extension into maxillary sinus. The efficacy of surgical treatment is demonstrated. Excision of the mass was two-staged, the first performed by ophthalmologist and the second performed by ENT-specialist. Orbital implant was used to close bone defect after the mass was removed.
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Necrotizing infection of soft tissues as the complication of perforating tumor of sigmoid colon
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01.01.2018 |
Lipatov K.
Komarova E.
Borodin A.
Struchkov Y.
Frolkov V.
Kirillin A.
Kiryupina M.
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Novosti Khirurgii |
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0 |
Ссылка
© 2018 Vitebsk State Medical University. All rights reserved. This clinical case demonstrates the development of severe streptococcal (Streptococcus pyogenes) necrotizing soft tissue infection as a result of perforation of the sigmoid neoplasm. The rapidly progressive necrotic process in the soft tissues of the lumbar and gluteal region as well as necrotic process in the left thigh (with the predominant lesion of the superficial fascia, subcutaneous fat and skin) led to the formation of an extensive postnecrectomic wound defect with an area of more than 1000 square centimeters. In addition to the severity of illness, the patient's belated treatment and the underestimation of the clinical situation by surgeons who provided emergency care contributed to such an extensive spread of the pathological process. The development of sepsis was accompanied by severe multiple organ failure. Because of the severity of the patient's condition, the surgical removal of the sigmoid neoplasm extended in the abdomen wall became possible only after its stabilization as a result of surgical focal sanation and complex intensive therapy in the conditions of the ICU. The most important point of the stage-by-stage surgical treatment was the choice of methods for the plastic closure of an extensive postnecrectomic wound that involved the entire left gluteal region, part of the lumbar and antero-inner surface of the left thigh. Taking into account the size and localization of the defect, the plastic reserves of the surrounding skin, the wound was closed in three stages with the help of combined plastic surgery techniques: with local tissues by the method of tissue expansion and a split-thickness skin graft.
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