Do autoantibody-responses mature between presentation with arthralgia suspicious for progression to rheumatoid arthritis and development of clinically apparent inflammatory arthritis? A longitudinal serological study

Pathophysiology and treatment of rheumatic disease

Radiofrequency ablation versus hepatic resection for hepatocellular carcinoma within the Milan criteria – A comparative study

AbstractBackgroundTo compare the results of radiofrequency ablation (RFA) with hepatic resection in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria.MethodsA nonrandomized comparative study was performed with 111 consecutive patients who underwent laparoscopic RFA (n = 31) or curative hepatic resection (n = 80) for HCC within Milan criteria.ResultsProcedure related complications were less often and severe after RFA than resection (3.2% vs. 25%). There was no significant difference in hospital mortality (0% vs. 3.8%). Hospital stay was significantly shorter in the RFA group than in the resection group (mean, 3.8 vs. 6.8 days). The 1-, 3-, and 5-year disease-free survival rates for the RFA group and the resection group were 76%, 40%, 40% and 76%, 60%, 60%, respectively. Disease-free survival was significantly lower in the RFA group than in the resection group. The corresponding 1-, 3-, and 5-year overall survival rates for the RFA group and the resection group were 100%, 92%, 84%, and 92%, 75%, 71%, respectively. The overall survival for RFA and resection were not significantly different.ConclusionsOur result showed comparable overall survival between RFA and surgery, although RFA was associated with a significantly higher tumor recurrence rate. RFA had the advantages over surgical resection in being less invasive and having lower morbidity

Human mast cells costimulate T cells through a CD28-independent interaction

Pathophysiology and treatment of rheumatic disease

Differential TLR-induced cytokine production by human mast cells is amplified by Fc epsilon RI triggering

Pathophysiology and treatment of rheumatic disease

Expansion of Th17 Cells by Human Mast Cells Is Driven by Inflammasome-Independent IL-1 beta

Pathophysiology and treatment of rheumatic disease

The Effect of Rituximab on B Cells in Skin and Peripheral Blood in Systemic Sclerosis

Dermatology-oncolog

Fc gamma RIIB regulates autoantibody responses by limiting marginal zone B cell activation

Fc gamma RIIB is an inhibitory receptor expressed throughout B cell development. Diminished expression or function is associated with lupus in mice and humans, in particular through an effect on autoantibody production and plasma cell (PC) differentiation. Here, we analyzed the effect of B cell-intrinsic Fc gamma RIIB expression on B cell activation and PC differentiation. Loss of Fc gamma RIIB on B cells in Fcgr2b-conditional KO (Fcgr2b-cKO) mice led to a spontaneous increase in autoantibody titers. This increase was most striking for IgG3, suggestive of increased extrafollicular responses. Marginal zone (MZ) B cells had the highest expression of Fc gamma RIIB in both mice and humans. This high expression of Fc gamma RIIB was linked to increased MZ B cell activation, Erk phosphorylation, and calcium flux in the absence of Fc gamma RIIB triggering. We observed a marked increase in IgG3+ PCs and B cells during extrafollicular PC responses in Fcgr2b-cKO mice. The increased IgG3 response following immunization of Fcgr2b-cKO mice was lost in MZ-deficient Notch2 Fcgr2b-double KO mice. Importantly, patients with systemic lupus erythematosus (SLE) had a decrease in Fc gamma RIIB expression that was strongest in MZ B cells. Thus, we present a model in which high Fc gamma RIIB expression in MZ B cells prevented their hyperactivation and ensuing autoimmunity

Fc gamma RIIB regulates autoantibody responses by limiting marginal zone B cell activation

Fc gamma RIIB is an inhibitory receptor expressed throughout B cell development. Diminished expression or function is associated with lupus in mice and humans, in particular through an effect on autoantibody production and plasma cell (PC) differentiation. Here, we analyzed the effect of B cell-intrinsic Fc gamma RIIB expression on B cell activation and PC differentiation. Loss of Fc gamma RIIB on B cells in Fcgr2b-conditional KO (Fcgr2b-cKO) mice led to a spontaneous increase in autoantibody titers. This increase was most striking for IgG3, suggestive of increased extrafollicular responses. Marginal zone (MZ) B cells had the highest expression of Fc gamma RIIB in both mice and humans. This high expression of Fc gamma RIIB was linked to increased MZ B cell activation, Erk phosphorylation, and calcium flux in the absence of Fc gamma RIIB triggering. We observed a marked increase in IgG3+ PCs and B cells during extrafollicular PC responses in Fcgr2b-cKO mice. The increased IgG3 response following immunization of Fcgr2b-cKO mice was lost in MZ-deficient Notch2 Fcgr2b-double KO mice. Importantly, patients with systemic lupus erythematosus (SLE) had a decrease in Fc gamma RIIB expression that was strongest in MZ B cells. Thus, we present a model in which high Fc gamma RIIB expression in MZ B cells prevented their hyperactivation and ensuing autoimmunity.Pathophysiology and treatment of rheumatic disease

Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium (Retracted article. See vol. 17, pg. 354, 2015)

Introduction: Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17 is an important inflammatory mediator. Recent data suggest that the synovial mast cell is a main producer of IL-17, although T cells have also been implicated as prominent IL-17 producers as well. We aimed to identify IL-17 expression by mast cells and T cells in synovium of arthritis patients.Methods: Synovial samples of anticitrullinated protein antibody-positive (ACPA+) and ACPA-negative (ACPA-) RA and osteoarthritis (OA) patients were stained for IL-17 in combination with CD117 (mast cells), CD3 (T cells) and CD68 (macrophages). Concentrations of IL-17 in synovial fluid were determined by ELISA.Results: The number of IL-17+ cells in synovium was comparable in all groups. Although the vast majority of IL-17+ cells are mast cells, no difference in the percentage of IL-17+ mast cells was observed. Nonetheless, levels of IL-17 in synovial fluid were increased in ACPA+ RA patients compared to ACPA-RA and OA patients.Conclusions: The synovial mast cell is the main IL-17+ cell in all three arthritis groups analyzed. These data are relevant for studies aimed at blocking IL-17 in the treatment of arthritis.Pathophysiology and treatment of rheumatic disease