AbstractDiagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α1-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α1-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α1-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α1-AT concentration as independently predicting SR-GVHD together with initial stage > 2 GI-GVHD. Our results showed that fecal calprotectin and α1-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.

Transcranial magnetic stimulation (TMS) can be used to study sensorimotor integration in humans non-invasively. Motor excitability has been found to be inhibited when afferent stimuli are given to a peripheral nerve and precede TMS at interstimulus intervals (ISIs) of 20-50 ms. This phenomenon has been referred to as short-latency afferent inhibition (SAI). To better understand the functional meaning of these phenomena, we examined the effect of the size of the receptive field on SAI to cutaneous afferents in upper-limb sensorimotor areas in humans. We examined the effect of the stimulation of the isolated right first (D1), second (D2) and third finger (D3), the right second and third finger together (D23) and the right first three fingers together (D123) on the amplitude of motor evoked potentials (MEPs) to TMS in hand and forearm muscles. We examined the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles. Digital stimulation preceded TMS at ISIs of 20-50 ms. The effect of D2 stimulation was MEP inhibition (SAI), which was more marked and consistent in APB and FDI muscles than in ECR and FCR muscles. Similarly, D1 and D3 stimulation caused MEP reduction, while no MEP enhancement could be found to single finger stimulation. In contrast, D123 stimulation induced less effective SAI in upper-limb muscles. MEP potentiation was recorded in some muscles to D123 stimulation. A significant difference between D2 and D123 stimulation was found in APB (ISIs = 30-50 ms) and FDI (ISIs = 40-50 ms) muscles, but not in forearm muscles. The effect to D23stimulation on MEP amplitude was intermediate between those to D2 and D123 stimulation. Our data suggest that motor excitability to cutaneous afferents may be influenced by the size of the receptive fields, this effect being the result of increasing convergence between hand afferents in the somatosensory system. These phenomena appear to be topographically arranged across the representation of upper-limb muscles. These findings may help to understand the functional significance of SAI in normal physiology and pathophysiology.