The onset of symptoms can range from weeks up to tens of years from the initial exposure. In some individuals, a single exposure to beryllium can cause berylliosis. Pathogenesis
In susceptible persons, beryllium exposure can lead to a cell-mediated immune response. The T-cells become sensitized to beryllium. Each subsequent exposure leads to an immune response involving CD4+ helper T-lymphocytes and macrophages accumulating in the lungs. As this response continues macrophages, CD+4 T-lymphocytes and plasma cells aggregate together to form the noncaseating granulomas. When beryllium is phagocytized by macrophages, the beryllium triggers macrophage apoptosis, thereby reducing beryllium clearance from the lungs and eventually resulting in secondary necrosis and lysis. Eventually, the outcome is fibrosis of the lung.Several studies have shown that there is a genetic component to beryllium sensitivity. Specifically, those beryllium exposed workers with a mutation at the HLA-DPB1 Glu69 position have increased prevalence of beryllium sensitization and CBD. The HLA-DPB1 gene is important for MHC class II molecule function on antigen presenting cells.According to the International Agency for Research on Cancer (IARC), beryllium and beryllium compounds are Category 1 carcinogens; they are carcinogenic to both animals and humans. Diagnosis
The differential diagnosis for berylliosis includes:
Sarcoidosis
Granulomatous lung diseases
Tuberculosis
Fungal infections (e.g., histoplasmosis)
Granulomatosis with polyangiitis
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
AsthmaOf these possibilities, berylliosis presents most similarly to sarcoidosis. Some studies suggest that up to 6% of all cases of sarcoidosis are actually berylliosis.Definitive diagnosis of berylliosis is based on history of beryllium exposures, documented beryllium sensitivity and granulomatous inflammation on lung biopsy.
: 160  CD3 is one of the proteins that make up the TCR complex. : 166  The TCR transduces the signal for the T cell to proliferate and attack the antigen. : 160 Muromonab-CD3 is a murine (mouse) monoclonal IgG2a antibody which was created using hybridoma technology. It binds to the T cell receptor-CD3-complex (specifically the CD3 epsilon chain) on the surface of circulating T cells, initially leading to an activation, but subsequently inducing the clearance of TCR complex from cell surface and apoptosis of the T cells. This protects the transplant against the T cells. When administered for transplant induction, the drug is administered daily thereafter for up to 7 days.Newer monoclonal antibodies in development with the same mechanism of action include otelixizumab (also known as TRX4), teplizumab (also known as hOKT3γ1(Ala-Ala) ), and visilizumab (with a tentative trade name of Nuvion). They are being investigated for the treatment of other conditions like Crohns disease, ulcerative colitis, and type 1 diabetes. Further development of teplizumab is uncertain, due to one-year data from a recent Phase III trial being "disappointing". Adverse effects
Especially during the first infusion, the binding of muromonab-CD3 to CD3 can activate T cells to release cytokines like tumor necrosis factor and interferon gamma. This cytokine release syndrome, or CRS, includes side effects like skin reactions, fatigue, fever, chills, myalgia, headaches, nausea and diarrhea, and could lead to life-threatening conditions like apnoea, cardiac arrest, and flash pulmonary edema.