Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor FcγRIIB

Rheumatoid arthritis (RA) is a complex autoimmune disease with a poorly understood pathogenesis. The disease is associated with polyclonal B cell activation and the production of autoantibodies (autoAbs), but there is a longstanding controversy as to whether such Abs contribute to, or are secondary to, the pathogenesis of RA. To address the potential pathogenicity of human RA–associated Abs, we developed a passive transfer model involving mice deficient in the low-affinity inhibitory Fc receptor, FcγRIIB. We report that plasma or serum from patients with active RA can induce inflammation and histological lesions in FcγRIIB−/− mice consistent with arthritis, and that this pathogenic activity is caused by the immunoglobulin G–rich fraction. Our results suggest that humoral autoimmunity can contribute directly to autoimmune arthritis, and that FcγRIIB−/− mice are a promising model to evaluate the arthritogenic potential of human autoAbs

The Role of Minor Histocompatibility Antigens in Tissue Transplant Rejection

Hematopoietic stem cell transplantation (HSCT) is an affective treatment for many malignant diseases including hematological malignancies, solid tumors that are sensitive to myeloablative therapy, non malignant diseases and severe autoimmune diseases. Graft versus host disease (GVHD) is the most serious and life-threatening complication post HSCT. The immune response that causes GVHD in HSCT between major histocompatibility complex matched donors and recipients are directed mainly against few immunodominant minor histocompatibility antigens (mHAgs) despite the presence of numerous other mHAgs. Remarkably \u3e30% of the total CD8+ T cells immune response to the mHAgs was directed against a single mHAg (H60). The mechanism by which H60 achieves its immunodominance is unknown. A major goal of the study is to investigate the mechanism by which H60 overwhelmingly dominates other mHAgs and determine the kinetics of CD8+ T cells immune response to various immunodominant mHAgs in immunization and GVHD settings. Furthermore, we sought to determine the relative impact of matching or mismatching of a single or multiple mHAgs in development of GVHD following bone marrow (BM) transplantation between MHC matched background disparate mouse strains. We generated H60 transgenic mice and a battery of congenic mice for single and multiple combinations of mHAgs and we performed several immunizations and BM and spleen cell transfers. We hypothesized that the immunodominance of H60 is due to the lack of self analog in the responding mice that cause loss of T cells negative selection in the thymus which lead to presence of high T cell precursor frequency specific for H60. Herein we show that introduction of self analog of H60 in mice that do not express H60 did not ameliorate their immune response to H60, thus we ruled out this mechanism for the immunodominance of H60. Furthermore, we show that any of the tested single mHAgs are not a risk factor for lethal GVHD; however, we show that matching for mHAgs resulted in the attenuation of GVHD. Understanding the mechanism of immunodominance is of importance in transplantation, immunotherapy targeting mHAgs in cancer treatment and vaccine development

Mpox Perceptions and Vaccine Advocacy among the Healthcare Workers of Solid Organ Transplant Centers: A Multicenter, Cross-Sectional Survey in Saudi Arabia

Background: In response to the global Mpox outbreaks, this survey aimed to assess the knowledge, perceptions, and advocacy of Mpox vaccines among solid organ transplant healthcare workers (HCWs) in Saudi Arabia. Methods: A cross-sectional survey was conducted among solid organ transplant HCWs in Saudi Arabia from 15 August to 5 September 2022. A total of 199 responses were received from participants primarily working in the kidney (54.8%) and liver (14.6%) transplant units. Results: The survey found that most participants were aware of the 2022 Mpox outbreak, but the majority were more concerned about COVID-19 than Mpox. While the majority of participants thought laboratory personnel and HCWs in direct contact with Mpox patients should receive the vaccine, less than 60% believed that all HCWs should be vaccinated. Additionally, over half of the participants lacked knowledge of animal–human transmission of the virus. Conclusion: The results highlight the need for increased education on Mpox among transplant HCWs in Saudi Arabia, particularly regarding the virus’s transmission dynamics and vaccines. This education is crucial to improve HCWs’ understanding of this emerging disease, especially given their vulnerability during the COVID-19 pandemic