Red blood cells in type 1 diabetes and multiple sclerosis and technologies to measure their emerging roles.

Autoimmune diseases affect over 40 million people in the United States. The cause of most autoimmune diseases is unknown; therefore, most therapies focus on treating the symptoms. This review will focus on the autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis (MS) and the emerging roles of red blood cells (RBCs) in the mechanisms and treatment of T1D and MS. An understanding of the role of the RBC in human health is increasing, especially with respect to its role in the regulation of vascular caliber and vessel dilation. The RBC is known to participate in the regulation of blood flow through the release of key signaling molecules, such as adenosine triphosphate (ATP) and the potent vasodilator nitric oxide (NO). However, while these RBC-derived molecules are known to be determinants of blood flow in vivo, disruptions in their concentrations in the circulation are often measured in common autoimmune diseases. Chemical and physical properties of the RBC may play a role in autoimmune disease onset, especially T1D and MS, and complications associated with downstream extracellular levels of ATP and NO. Finally, both ATP and NO are highly reactive molecules in the circulation. Coupled with the challenging matrix posed by the bloodstream, the measurement of these two species is difficult, thus prompting an appraisal of recent and novel methods to quantitatively determining these potential early indicators of immune response.

Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

Commissural communication allows mouse intergeniculate leaflet and ventral lateral geniculate neurons to encode interocular differences in irradiance.

KEY POINTS: Unlike other visual thalamic regions, the intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) possess extensive reciprocal commissural connections, the functions of which are unknown. Using electrophysiological approaches, it is shown that commissural projecting IGL/vLGN cells are primarily activated by light increments to the contralateral eye while cells receiving commissural input typically exhibit antagonistic binocular responses. Across antagonistic cells, the nature of the commissural input (excitatory or inhibitory) corresponds to the presence of ipsilateral ON or OFF visual responses and in both cases antagonistic responses disappear following inactivation of the contralateral thalamus. The steady state firing rates of antagonistic cells uniquely encode interocular differences in irradiance. There is a pivotal role for IGL/vLGN commissural signalling in generating new sensory properties that are potentially useful for the proposed contributions of these nuclei to visuomotor/vestibular and circadian control. ABSTRACT: The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) are portions of the visual thalamus implicated in circadian and visuomotor/vestibular control. A defining feature of IGL/vLGN organisation is the presence of extensive reciprocal commissural connections, the functions of which are at present unknown. Here we use a combination of multielectrode recording, electrical microstimulation, thalamic inactivation and a range of visual stimuli in mice to address this deficit. Our data indicate that, like most IGL/vLGN cells, those that project commissurally primarily convey contralateral ON visual signals while most IGL/vLGN neurons that receive this input exhibit antagonistic binocular responses (i.e. excitatory responses driven by one eye and inhibitory responses driven by the other), enabling them to encode interocular differences in irradiance. We also confirm that this property derives from commissural input since, following inactivation of the contralateral visual thalamus, these cells instead display monocular contralateral-driven ON responses. Our data thereby reveal a fundamental role for commissural signalling in generating new visual response properties at the level of the visual thalamus.