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OBJECTIVES: While myeloid-derived suppressor cells (MDSCs) were previously shown to promote a proinflammatory T helper (Th) 17 response in autoimmune conditions, a potential impact of the MDSC-Th17 immune axis on abnormal bone destruction in RA remains largely unknown. METHODS: We investigated the correlation between the frequency of MDSCs or its subsets and joint destruction in RA patients. The reciprocal actions of patient-derived MDSCs and Th17 cells were studied using osteoclast (OC) differentiation and bone resorption assays in vitro, which were further validated using mouse models of RA. Contribution of MDSCs to osteoclastogenesis and bone erosion in vivo was determined by depletion or transfer of MDSCs. RESULTS: Human MDSCs, particularly monocytic MDSCs (M-MDSCs), exhibit inherent OC-differentiating capacity and positively correlate with clinical bone erosion in RA patients. Strikingly, patient-derived M-MDSCs can program Th17 cells towards a pro-osteoclastogenic phenotype, which in return potentiates OC differentiation via the receptor activator of nuclear factor κΒ ligand (RANK-L)-RANK signalling. This enhanced osteolysis driven by the reciprocal actions of M-MDSCs and Th17 cells is further confirmed using mouse models of RA. Selective depletion of M-MDSCs significantly ameliorates osteoclastogenesis and disease severity in arthritic mice, whereas transfer of M-MDSCs aggravates bone erosion associated with increased OCs in recipient mice. CONCLUSION: Our findings highlight the functional plasticity of MDSCs and identify a novel pro-osteoclastogenic pathway governed by interplay between myeloid cells and T lymphocytes in autoimmune RA.

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Since the original recognition of these conditions in 1961, a great deal has been learned about the pathogenesis, clinical manifestations, and appropriate treatment of gout and pseudogout, and the role of crystals in osteoarthritis has been further defined. The variable manifestations of crystal-induced arthritis in elderly populations has led to a greater need for proper diagnosis and treatment strategies for these increasingly common forms of arthritis.

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Since the original descriptions of the involvement of crystals in arthritis, our understanding of the clinical syndromes of gout and pseudogout, and the role of basic calcium crystals in arthritis has increased. Gout is usually considered an affliction confined to middle-aged men, but has an increasing prevalence in older populations, with unique and often atypical features. Calcium pyrophosphate dihydrate crystal deposition disease is common in elderly patients. The diagnosis of both of these common forms of arthritis and the need to individualize therapy in patients with other medical problems remain important clinical challenges to the practicing physician.

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A case of granulomatous myositis as a manifestation of chronic graft-versus-host disease is presented. The clinical presentation, MR imaging appearances, pathologic features and excellent response to treatment with immunosuppression are described. To the best of our knowledge, based on a world literature search, this is the first report of graft-versus-host disease presenting as granulomatous polymyositis.,

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Synovial fluid white blood cell counts are considered to be useful in diagnosing infectious arthritis, however, considerable overlap exists between infectious and noninfectious types of inflammatory arthritis. We undertook this review of synovial fluid studies at our institution to better define this degree of overlap and characterize the features of infectious arthritis in relationship to synovial fluid white cell counts. The records of 202 consecutive patients with synovial fluid white blood cell counts >2000/mm were reviewed. Infectious arthritis was diagnosed in 77% (10/13) of patients with counts >100,000, 47% (8/17) in the 50,000-100,000 range, and 5% (9/172) with counts <50,000. Crystal-induced arthritis and rheumatoid arthritis made up 81% of patients in the 15,000-50,000 range. Overall, 10 of 27 (37%) cases of infectious arthritis had white cell counts >100,000, and 18 of 27 (67%) had counts >50,000. A majority of these infections (14/18) were related to Staphylococcus aureus, while 5 of 7 infections associated with counts <20,000 were associated with atypical organisms. This study confirms that a majority of patients with very high synovial fluid white blood cell counts have infectious arthritis, and that the likelihood of infection is markedly reduced, but certainly not excluded, below this level. The presence of atypical infections in a small percentage of patients with low counts emphasizes the importance of clinical judgment in evaluating all patients with inflammatory arthritis, regardless of synovial fluid white cell counts.