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Several recent studies have demonstrated the central role of Fc receptors (FcR) rather than the complement system in triggering hypersensitivity reactions. We investigated the role of FcR for IgG (FcγR) using a murine model of accelerated anti‐glomerular basement membrane (GBM) antibody‐mediated glomerulonephritis as a representative of type II hypersensitivity diseases. Intravenous injection of rabbit anti‐GBM antibody after preimmunization with normal rabbit IgG induced proteinuria and azotemia in wild‐type C57BL / 6 and CD40+ / – mice but not in FcR γ chain (FcRγ)– / – mice or CD40– / – mice. Light microscopic findings revealed marked tissue damage in the glomeruli of wild‐type C57BL / 6 and CD40+ / – mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glomeruli of FcRγ– / – mice. The glomeruli of CD40– / – mice were almost normal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti‐GBM antibody. However, depositions of mouse IgG and complement to the glomeruli were not observed in CD40– / – mice, and deposition of fibrin was not observed in FcRγ– / – or CD40– / – mice. These findings suggest that FcγR may initiate anti‐GBM antibody‐mediated renal disease. We conclude that FcγR rather than the complement system is critically involved in the development of type II hypersensitivity diseases.

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Background Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. Subjects, Materials, and Methods In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self‐assessment questionnaire to determine whether the patients believed oral morphine was effective. Results Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty‐four patients (76.1%) reported that oral morphine was effective on the self‐assessment questionnaire. Among the background factors, a high score for “sense of discomfort” on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack‐years were associated with greater effectiveness. Conclusion Oral morphine was effective and feasible for treating cancer‐related dyspnea. A higher score for “sense of discomfort” on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. Implications for Practice This study demonstrated that oral morphine was effective in alleviating cancer‐related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for “sense of discomfort” on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in “morphine‐ineffective” patients.

Anaphylaxis denotes an immediate hypersensitivity reaction to allergen, exclusively mediated by IgE antibodies. However, IgE antibodies do not explain all the syndromes that are encountered. We investigated potent IgG-mediated anaphylaxis in CD40-deficient mice that lack the immunoglobulin class switching for T cell-dependent antigens. Immunization with ovalbumin did not induce either humoral responses of IgG, IgA, and IgE, or systemic anaphylaxis in CD40-deficient mice. Although systemic anaphylaxis by active immunization was not observed in CD40-deficient mice, both passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis assessed by mouse blood pressure monitoring with cervical artery catheterization did take place when antigen-specific IgG was transferred and then antigen challenge given. Further, to investigate the inflammatory pathway of IgG-mediated immediate hypersensitivity reactions, we focused on the Fc gamma receptor (Fc gammaR) function. Pretreatment of the mice with the anti-Fc gammaRII/Fc gammaRIII MoAb clearly blocked the response of PCA and passive systemic anaphylaxis, suggesting that they were initiated through Fc gammaR. In conclusion, we directly demonstrate the IgG-mediated anaphylaxis and its triggering mechanism through Fc gammaR in in vivo conditions. In addition to IgE-mediated anaphylaxis, IgG-mediated anaphylaxis should be considered and the blocking of Fc gammaR would provide one of the therapeutic targets for the control of IgG-mediated hypersensitivity diseases.