BACKGROUND: Approximately 40% to 50% of patients with chronic idiopathic urticaria (CIU) have functional IgG autoantibodies against FcepsilonRIalpha or IgE, which induce histamine release from basophils and cutaneous mast cells. A positive autologous serum skin test response is believed to reflect the presence of these autoantibodies. OBJECTIVE: We sought to further define the functional properties of and develop a sensitive functional assay for detection of autoantibodies in patients with CIU. METHODS: Sera from patients with CIU (n=61) and sera from healthy control subjects (n=23) were incubated with donor basophils. Activation of basophils was determined on the basis of CD 63 surface expression, as analyzed on a FACScan flow cytometer. RESULTS: A positive basophil activation test result was found in 51% of patients with CIU, and basophil-activating properties were present in the IgG fractions of sera. When both the in vitro test and the autologous serum skin test were considered, basophil/mast cell-activating autoantibodies were present in 62% of the patients. Patients with a positive basophil activation test result had a significantly higher prevalence of other autoantibodies, had more severe urticaria, and were more likely to have angioedema. CONCLUSION: The results demonstrate the presence of basophil-activating autoantibodies in about 50% of patients with CIU. The data support the autoimmune cause of the disease and provide a simple test for detection of these autoantibodies.
BACKGROUND: Approximately 40% to 50% of patients with chronic idiopathic urticaria (CIU) have functional IgG autoantibodies against FcepsilonRIalpha or IgE, which induce histamine release from basophils and cutaneous mast cells. A positive autologous serum skin test response is believed to reflect the presence of these autoantibodies. OBJECTIVE: We sought to further define the functional properties of and develop a sensitive functional assay for detection of autoantibodies in patients with CIU. METHODS: Sera from patients with CIU (n=61) and sera from healthy control subjects (n=23) were incubated with donor basophils. Activation of basophils was determined on the basis of CD 63 surface expression, as analyzed on a FACScan flow cytometer. RESULTS: A positive basophil activation test result was found in 51% of patients with CIU, and basophil-activating properties were present in the IgG fractions of sera. When both the in vitro test and the autologous serum skin test were considered, basophil/mast cell-activating autoantibodies were present in 62% of the patients. Patients with a positive basophil activation test result had a significantly higher prevalence of other autoantibodies, had more severe urticaria, and were more likely to have angioedema. CONCLUSION: The results demonstrate the presence of basophil-activating autoantibodies in about 50% of patients with CIU. The data support the autoimmune cause of the disease and provide a simple test for detection of these autoantibodies.
Authors: Martin Metz; Gordon Sussman; Rémi Gagnon; Petra Staubach; Tonny Tanus; William H Yang; Jeremy J Lim; Holly J Clarke; Joshua Galanter; Leslie W Chinn; Tom Chu; Anastasia Teterina; Tracy Burgess; D James Haddon; Timothy T Lu; Marcus Maurer Journal: Nat Med Date: 2021-11-08 Impact factor: 53.440