Biomedical subjects

Anne Schaefer

Publications and source records attributed to Anne Schaefer.

5 recordsLinked to original sources

PubMed2025

Lymphoid gene expression supports neuroprotective microglia function.

Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)1. The microglial response to amyloid plaques in AD can range from neuroprotective to neurotoxic2. Here we show that the protective function of microglia is governed by the transcription factor PU.1, which becomes downregulated following microglial contact with plaques. Lowering PU.1 expression in microglia reduces the severity of amyloid disease pathology in mice and is linked to the expression of immunoregulatory lymphoid receptor proteins, particularly CD28, a surface receptor that is critical for T cell activation3,4. Microglia-specific deficiency in CD28, which is expressed by a small subset of plaque-associated PU.1low microglia, promotes a broad inflammatory microglial state that is associated with increased amyloid plaque load. Our findings indicate that PU.1low CD28-expressing microglia may operate as suppressive microglia that mitigate the progression of AD by reducing the severity of neuroinflammation. This role of CD28 and potentially other lymphoid co-stimulatory and co-inhibitory receptor proteins in governing microglial responses in AD points to possible immunotherapy approaches for treating the disease by promoting protective microglial functions.

Microglia↗

PubMed2006

CT angiography in acute stroke: does it provide additional information on occurrence of infarction and functional outcome after 3 months?

OBJECTIVE: To investigate whether acute phase intracranial CT angiography (CTA) independently predicts infarction and functional outcome in ischemic stroke. METHODS: Hundred and fifty-one consecutive patients with acute (<12 h) ischemic stroke who received intracranial CTA were investigated. Stroke severity on admission was determined using the National Institute of Health Stroke Scale (NIHSS). Reconstructed CTAs were investigated for relevant pathology. Follow-up imaging was performed 24-48 h after admission. Functional outcome was assessed after 3 months using the modified Rankin scale. Single factor and multiple logistic regression analyses were performed to predict infarction and dependency (modified Rankin scale > or = 3) on follow-up. RESULTS: Median NIHSS on admission was 10 (IQR 3-14). Out of the 151 patients, 61 (40%) had pathological CTA findings. Infarction was demonstrated in 60/61 patients (98%) with and in 67/90 patients (74%) without vessel pathology. Presence of infarction on follow-up imaging and dependency at 3 months were correlated with pathological CTA findings on admission in single factor analysis (each p < 0.001). After adjustment for age (> or =/<65 years), NIHSS (> or =/<10), sex, therapy, and time to presentation (> or =/<3 h), only NIHSS > or = 10 on admission was predictive of dependency at follow-up (p < 0.001). CONCLUSIONS: Pathological CTA findings in the acute phase of ischemic stroke do not independently predict a poor outcome at 3 months after acute stroke.

Acute Disease↗

PubMed2003

Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies.

Human B cells that coexpress surrogate and conventional light chains (V-preB+L+) show an unusual heavy and light chain antibody repertoire that display evidence of receptor editing. However, it is unclear whether V-preB+L+ B cells have been silenced by receptor editing or still express autoreactive antibodies. Here we report that 68% of the antibodies expressed by V-preB+L+ B cells are autoreactive. A majority of these autoantibodies are true antinuclear antibodies (ANA), and 50% of the ANAs are also reactive with a diverse group of antigens that include dsDNA, ssDNA, immunoglobulin, insulin, and bacterial lipopolysaccharide. Such antibodies are rarely encountered among conventional B cells. We conclude that V-preB+L+ B cells are a unique subset of normal circulating human B cells that escape central tolerance mechanisms and express self-reactive antibodies including potentially harmful ANAs.

Amino Acid Sequence↗

PubMed2003

Predominant autoantibody production by early human B cell precursors.

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.

Antibodies, Antinuclear↗

PubMed2003

High-dose cyclophosphamide does not eradicate paroxysmal nocturnal haemoglobinuria haematopoiesis in mice carrying a Piga gene mutation.

Recently, high-dose cyclophosphamide (HD CY) has been used in the treatment of aplastic anaemia. Several reports have suggested that the treatment may either eradicate or suppress mutant clonal haematopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH). We therefore treated mice that have a proportion of blood cells deficient in GPI-anchor molecules (PIGA-) with HD CY, and monitored their peripheral blood counts during and after treatment. HD CY produced a transient myelosuppression; however, the contribution of PIGA- haematopoiesis to the peripheral blood remained unchanged, suggesting that HD CY is unlikely to eliminate an existing PNH clone in patients treated for aplastic anaemia.

Animals↗