Composition of the CD27+ Memory-B-Cell Compartment Delineates Immunoglobulin Deficiency Endotypes.

Abstract Purpose: The finding of reduced numbers of class-switched memory B cells (CSM) in peripheral blood is widely used to assist the diagnosis and subclassification of CVID. Limited data exists on this finding in relation to the entire class of PADs. In this study, consecutive 8-marker comprehensive B-cell panel results were analyzed to determine how reduced CSM quantities might inform the pathophysiology of CVID and other humoral immunodeficiencies. Methods: Subpopulations of CD27+ memory B cells from 64 consecutive subjects with or without humoral immunodeficiency were examined to identify associations with diagnosis and serum immunoglobulin level. Results: CD27+IgM-IgD- percentage (CSM%) was correlated with IgG level in a discontinuous manner with an estimated change point of 9.7% (95% CI: 4.7, 12.4). All subjects with a CSM% below 9.7% had substantially lower serum IgG and IgA levels compared with those above 9.7. CSM% below 9.7% is not associated with serum IgM level. Rather, the proportion of CD27+IgMonly B cells (IgMonly or IgMonly%) is correlated with serum IgM. Conclusion: Low CSM% may mark an endotype of humoral immune dysfunction defined by either loss of class switching or critical failure of the coordinated production of both memory cells and long-lived plasma cells responsible for adequate immunoglobulin levels in humans. In patients with low CSM%, maintenance or expansion of IgMonly cells and IgM production suggests the former explanation, while concomitant loss of IgMonly cells suggests the latter. These findings provide a simple endotypic stratification method for future studies on the failed coordinated B cell response in humans with PAD.

Predicting physical distancing on recreational trails during COVID-19.

The emergence of Coronavirus 19 led to societal and behavioral changes, including intensified use of many public parks and trails for mental respite and leisure time physical activity. As visitors sought stress-relief in the great outdoors, they also encountered stressful situations as they navigated risk exposure. Recommendations to physically distance between parties was a key component to reduce risk, but compliance is unknown in the outdoor arena. This observational study of more than 10 000 trail user encounters documented distancing and enabled predictive analysis that revealed wider trails, smaller groups and signage led to greater distancing compliance. Managers and planners can integrate these findings immediately and in consideration of future trail designs to minimize risk exposure. Management implications: Select site features increase odds of distancing compliance and can inform management decisions and designs immediately and in addressing future use surges: wider trails, unpaved surfaces, and COVID-19 signage.As distancing compliance waned with time but signage increased compliance, innovative and dynamic signs may sustain compliance and multi-media communications should be considered.Both activity size and group type influence distancing so considering group size recommendations and activity separation are in order.

Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis.

Background/Purpose: In rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likelihood and timing of future clinical RA. Materials and Methods: We evaluated relationships between ACPA, the shared epitope (SE), RF isotypes and incident RA in a prospective cohort of 90 ACPA(+) individuals without baseline arthritis identified through health-fair testing (i.e. Healthfair). We also evaluated ACPA and RF isotypes and time-to-diagnosis of RA in a retrospective cohort of 215 individuals with RA from the Department of Defense Serum Repository (DoDSR). Results: Twenty-six of 90 (29%) of ACPA(+) Healthfair participants developed incident RA. Baseline or incident dual RF-IgA and RF-IgM positivity was associated with increased risk for incident RA (HR 3.09; 95% CI 1.15 to 8.29) although RFs were negative in ~50% of individuals with incident RA. SE was associated with increased risk of RA (HR 2.87, 95% CI 1.22-6.76). In the DoDSR cohort, triple positivity for ACPA, RF-IgA and RF-IgM was present a median of 1-2 years prior to RA diagnosis, with some sex-specific differences. Conclusion: These findings can be used to counsel individuals at-risk for future RA and to design clinical trials for RA prevention. The findings also suggest that RF could be a surrogate outcome as a success of an immunologic intervention in RA prevention. Additional studies are needed to understand the biologic of different patterns of autoantibody elevations in RA evolution.