VH2+ Antigen-Experienced B Cells in the Cerebrospinal Fluid Are Expanded and Enriched in Pediatric Anti-NMDA Receptor Encephalitis.

Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti-NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti-NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti-NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti-NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti-NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti-NMDAR-AE patients may be relevant for clinical diagnosis and treatment.

Predictive Modeling for West Nile Virus and Mosquito Surveillance in Lubbock, Texas.

West Nile virus (WNV) was first detected in North America during 1999, and has since spread throughout the contiguous USA. West Nile virus causes West Nile fever and the more severe West Nile neuroinvasive disease. As part of a WNV vector surveillance program, we collected mosquitoes in Lubbock, Texas, using CO2-baited encephalitic vector survey (EVS) traps. During 219 wk from 2009 through 2017, EVS traps were operated for 1,748 trap nights, resulting in more than 101,000 mosquitoes captured. Weekly, selected female mosquito specimens were pooled by species and trap site, and screened for WNV using reverse transcription-polymerase chain reaction assay. Mosquitoes positive for WNV were detected during 16.9% (37/219) of the weeks. Using this information, we constructed a statistical model to predict the probability of detecting an infection within a mosquito pool as a factor of weather variables. The final model indicated that detection of WNV in mosquitoes was negatively associated with the week of year squared and average wind from 3 wk prior to sampling, and was positively associated with week of year, average visibility, average humidity from 2 wk prior to sampling, and average dew point from 4 wk prior to sampling. The model developed in this study may aid public health and vector control programs in swift and effective decision making relative to city-wide mosquito control efforts by predicting when the chances of mosquitoes having WNV are at their greatest.