AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to...AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers.Blood samples were stimulated with brimonidine 0.15%,timolol 0.5%or brimonidine tartrate/timolol maleate 0.2%/0.5%.Premixed antibodies(CD63/FITC and aIgE/PE)were added for direct staining and whole-blood samples were lysed,fixed and analyzed by a flow cytometer.The basophil population was defined by high IgE cell expression.Degranulation was identified by the expression of the activation molecule CD63.RESULTS:Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine(2.58%,2.45%,respectively,P=0.72).There was a significant suppression of basophil activation when a combination of brimonidine-timolol(0.87%)was compared to timolol(2.27%;P=0.012)and to brimonidine alone(2.58%;P=0.017).CONCLUSION:The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction.Basophil activation was suppressed by the presence ofβ-blockers in patients hypersensitive to brimonidine and in healthy individuals.This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.展开更多
Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed aut...Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed autoimmune pathophysiology of dysregulation in NT1;however,is the subject of ongoing speculation and debate with advances in gene sequencing and technology.Here,we present a case of a patient with concomitant refractory AD and NT1 and review the current research on their immunological relationship and the challenges in management relative to disease burden and psychiatric comorbidities.展开更多
Hajdu-Cheney syndrome （HCS） is a rare disorder which is characterized by developmental delay, craniofacial anomalies, congenital heart defects, hearing deficit, polycystic kidneys, and bone abnormalities, including ...Hajdu-Cheney syndrome （HCS） is a rare disorder which is characterized by developmental delay, craniofacial anomalies, congenital heart defects, hearing deficit, polycystic kidneys, and bone abnormalities, including progressive osteoporosis, acroosteolysis, wormian bones, and abnormal bonefractures.展开更多
Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic heterogeneity.Utilizing the current gold standard of whole ...Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic heterogeneity.Utilizing the current gold standard of whole exome sequencing for diagnosis,pathogenic gene variants are only identified in less than 20% of patients.While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis,many other genes may remain as yet undefined to enable definitive diagnosis,prognostic monitoring and targeted therapy of patients.Considering that many patients display a relatively late onset of disease presentation in their 2^(nd) or 3^(rd) decade of life,it is questionable whether a single genetic lesion underlies disease in all patients.Potentially,combined effects of other gene variants and/or non-genetic factors,including specific infections can drive disease presentation.In this review,we define(1)the clinical and immunological variability of PAD,(2)consider how genetic defects identified in PAD have given insight into B-cell immunobiology,(3)address recent technological advances in genomics and the challenges associated with identifying causal variants,and(4)discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates,improved prognostic monitoring and personalized medicine for PAD patients.A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.展开更多
文摘AIM:To evaluate the mechanism of which brimonidine tartrate 0.15%causes clinical hypersensitivity.METHODS:A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers.Blood samples were stimulated with brimonidine 0.15%,timolol 0.5%or brimonidine tartrate/timolol maleate 0.2%/0.5%.Premixed antibodies(CD63/FITC and aIgE/PE)were added for direct staining and whole-blood samples were lysed,fixed and analyzed by a flow cytometer.The basophil population was defined by high IgE cell expression.Degranulation was identified by the expression of the activation molecule CD63.RESULTS:Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine(2.58%,2.45%,respectively,P=0.72).There was a significant suppression of basophil activation when a combination of brimonidine-timolol(0.87%)was compared to timolol(2.27%;P=0.012)and to brimonidine alone(2.58%;P=0.017).CONCLUSION:The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction.Basophil activation was suppressed by the presence ofβ-blockers in patients hypersensitive to brimonidine and in healthy individuals.This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.
文摘Atopic dermatitis(AD)and narcolepsy type 1(NT1)are two distinct diseases that have not been classically shown to be related.The potential connection between the known immunological aetiology of AD and the proposed autoimmune pathophysiology of dysregulation in NT1;however,is the subject of ongoing speculation and debate with advances in gene sequencing and technology.Here,we present a case of a patient with concomitant refractory AD and NT1 and review the current research on their immunological relationship and the challenges in management relative to disease burden and psychiatric comorbidities.
基金This research was supported by a grant from the National Natural Science Foundation of China （No. 81571605）.
文摘Hajdu-Cheney syndrome （HCS） is a rare disorder which is characterized by developmental delay, craniofacial anomalies, congenital heart defects, hearing deficit, polycystic kidneys, and bone abnormalities, including progressive osteoporosis, acroosteolysis, wormian bones, and abnormal bonefractures.
基金supported by The Jeffrey Modell Foundation and the Australian National Health and Medical Research Council(NHMRC,Senior Research Fellowship 1117687 to M.C.v2.).
文摘Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic heterogeneity.Utilizing the current gold standard of whole exome sequencing for diagnosis,pathogenic gene variants are only identified in less than 20% of patients.While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis,many other genes may remain as yet undefined to enable definitive diagnosis,prognostic monitoring and targeted therapy of patients.Considering that many patients display a relatively late onset of disease presentation in their 2^(nd) or 3^(rd) decade of life,it is questionable whether a single genetic lesion underlies disease in all patients.Potentially,combined effects of other gene variants and/or non-genetic factors,including specific infections can drive disease presentation.In this review,we define(1)the clinical and immunological variability of PAD,(2)consider how genetic defects identified in PAD have given insight into B-cell immunobiology,(3)address recent technological advances in genomics and the challenges associated with identifying causal variants,and(4)discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates,improved prognostic monitoring and personalized medicine for PAD patients.A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.
