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Breville, G.

Publications and source records attributed to Breville, G..

2 recordsLinked to original sources

Abnormal pro-inflammatory immune cell responses precede clinical onset of hypertensive disorders of pregnancy

BackgroundHypertensive disorders of pregnancy (HDP) are significant contributors to maternal morbidity and mortality as well as to long-term cardiovascular health, with an inequitable burden among Black individuals. While there is growing interest in the possibility that inflammatory responses are involved with HDP, work to date has primarily been cross-sectional, and immune cell profiling has focused on cell phenotyping that may not capture relevant functional properties of the immune cells. ObjectiveTo examine whether an inflammatory cellular response is found in the blood of pregnant women preceding the clinical onset of HDP. Study designThis nested case-control study included 27 pregnant women who later developed HDP and 73 who had a healthy pregnancy delivered at term, all of whom provided blood samples during the second trimester. ResultsWe observed a greater abundance of peripheral blood T cells in individuals later diagnosed with HDP. Among these were CD161+ CD4 T cells that showed increased expression of pro-inflammatory cytokines, including GM-CSF and TNF. Similarly, monocytes from these individuals exhibited increased expression of pro-inflammatory cytokines. Anti-inflammatory T cells and monocytes were not altered in those with versus without a future diagnosis of HDP. ConclusionWe identify a pro-inflammatory cellular immune signature in pregnant individuals destined to have HDP. Immune signatures may serve as a new biomarker to identify subsets of individuals at particular risk for HDP and/or point to new therapeutic targets to prevent HDP.

immunology↗

Pediatric cerebrospinal fluid immune profiling distinguishes pediatric-onset multiple sclerosis from other pediatric-onset acute neurological disorders

The cerebrospinal fluid (CSF) provides a unique glimpse into the central nervous system (CNS) compartment and offers insights into immune processes associated with both healthy immune surveillance as well as inflammatory disorders of the CNS. The latter include demyelinating disorders, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), that warrant different therapeutic approaches yet are not always straightforward to distinguish on clinical and imaging grounds alone. Here, we establish a comprehensive phenotypic landscape of the pediatric CSF immune compartment across a range of non-inflammatory and inflammatory neurological disorders, with a focus on better elucidating CNS-associated immune mechanisms potentially involved in, and discriminating between, pediatric-onset MS (MS) and other pediatric-onset suspected neuroimmune disorders, including MOGAD. We find that CSF from pediatric patients with non-inflammatory neurological disorders is primarily composed of non-activated CD4+ T cells, with few if any B cells present. CSF from pediatric patients with acquired inflammatory demyelinating disorders is characterized by increased numbers of B cells compared to CSF of both patients with other inflammatory or non-inflammatory conditions. Certain features, including particular increased frequencies of antibody-secreting cells (ASCs) and decreased frequencies of CD14+ myeloid cells, distinguish MS from MOGAD and other acquired inflammatory demyelinating disorders.

immunology↗