RESUMO
BACKGROUND: Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). METHODS: A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and ß1AR-AAb in serum. RESULTS: MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 â± â0.7 vs. 5.5 â± â0.9; P â= â0.044) and in controls (4.1 â± â0.5 vs. 3.9 â± â0.6; P â= â0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 â± â1.2 vs. 5.3 â± â1.0; P â< â0.001) and ß1AR-AAb (5.7 â± â1.8 vs. 4.1 â± â0.9; P â< â0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P â= â0.007) and ß1AR-AAb activity (52% vs. 2%; P â< â0.001). CONCLUSIONS: The co-presence of norepinephrine in serum samples can artifactually elevate α1AR and ß1AR activity, which can be avoided by serum pre-treatment with MAO. Using this novel bioassay, we show that POTS patients have increased α1AR-AAb and ß1AR-AAb activity compared to healthy controls in the largest POTS cohort reported to-date.
RESUMO
A distractor placed nearby a saccade target will cause interference during saccade planning and execution, and as a result will cause the saccade's trajectory to curve in a systematic way. It has been demonstrated that making a distractor more task-relevant, for example by increasing its similarity to the target, will increase the interference it imposes on the saccade and generate more deviant saccadic trajectories. Is the extent of a distractor's interference within the oculomotor system limited to its relevance to a particular current task, or can a distractor's general real-world meaning influence saccade trajectories even when it is made irrelevant within a task? Here, it is tested whether a task-irrelevant distractor can influence saccade trajectory if it depicts a stimulus that is normally socially relevant. Participants made saccades to a target object while also presented with a task-irrelevant (upright or inverted) face, or scrambled non-face equivalent. Results reveal that a distracting face creates greater deviation in saccade trajectory than does a non-face distractor, most notably at longer saccadic reaction times. These results demonstrate the sensitivity of processing that distractors are afforded by the oculomotor system, and support the view that distractor relevance beyond the task itself can also influence saccade planning and execution.
