ABSTRACT
OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66-77.
Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Small Fiber Neuropathy/immunology , Adult , Aged , Autoantibodies/blood , Cohort Studies , Female , Humans , Keratin-8/immunology , Male , Microfilament Proteins/immunology , Middle Aged , Myxovirus Resistance Proteins/immunology , Small Fiber Neuropathy/blood , src Homology Domains/immunologyABSTRACT
Impaired sense of smell occurs in a fraction of patients with COVID-19 infection, but its effect on cerebral activity is unknown. Thus, this case report investigated the effect of COVID-19 infection on frontotemporal cortex activity during olfactory stimuli. In this preliminary study, patients who recovered from COVID-19 infection (n = 6) and healthy controls who never contracted COVID-19 (n = 6) were recruited. Relative changes in frontotemporal cortex oxy-hemoglobin during olfactory stimuli was acquired using functional near-infrared spectroscopy (fNIRS). The area under curve (AUC) of oxy-hemoglobin for the time interval 5 s before and 15 s after olfactory stimuli was derived. In addition, olfactory function was assessed using the Sniffin' Sticks 12-identification test (SIT-12). Patients had lower SIT-12 scores than healthy controls (p = 0.026), but there were no differences in oxy-hemoglobin AUC between healthy controls and patients (p > 0.05). This suggests that past COVID-19 infection may not affect frontotemporal cortex function, and these preliminary results need to be verified in larger samples.
