Searching for highly sensitive and specific biomarkers for sepsis: State-of-the-art in post-mortem diagnosis of sepsis through immunohistochemical analysis

Abstract

The autoptical observations commonly ascribed to sepsis deal with unspecific general and local signs of inflammation or ischemia, such as myocardial inflammation, pulmonary edema and infiltration, cerebral swallowing, and tubular necrosis in the kidney. In the two last decades, some studies have been carried out to implement immunohistochemical markers for post-mortem diagnosis. All of these target molecules are specifically up-regulated or down-regulated during systemic inflammatory responses, especially for infective causes. Among these, we found some antigens expressed on leukocyte surfaces (very late antigen-4 (VLA-4), cluster differentiation-15 (CD15)), enzyme contained in neutrophils granules (lysozyme (LZ), lactoferrin (LF)), endothelial markers and junctions (E-selectin, vascular endothelial cadherin (VE-cadherin)), and soluble factors (vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1)). All of these showed potential reliability in differentiating sepsis cases from controls. Further studies are needed to provide a concrete validation for a combination of markers on specific organ samples in order to reach a post-mortem diagnosis of sepsis also in the absence of clinical records.

Post-Mortem Investigations for the Diagnosis of Sepsis: A Review of Literature

“…Several immunohistochemical markers to date were tested as possible post-mortem markers for the diagnosis of sepsis [ 3 , 4 , 12 , 14 , 21 , 27 , 28 , 29 ]. The lung, representing the mostly impaired organ in sepsis, has rapidly become the main target for immunohistochemical assays in order not only to improve the knowledge of sepsis pathophysiology, but also to establish whether an immunohistochemical marker exists, specific enough to allow a differential diagnosis between sepsis and non-sepsis fatalities within a medico-legal context [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] ( Table 3 ).…”

Oxidative Stress and Inflammation Interdependence in Multiple Sclerosis

“…[34]. Also, neutrophils granule contains enzyme-like lysozyme or lactoferrin which can be markers of organ-specific inflammation [35]. However, only limited studies described NLR association in MS diseases [36,37] and it is still a growing interest aiming to establish potential serological markers associated with a local and systemic inflammatory status that are cost-effective and minimally invasive.…”

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features

“…Regarding the assessment of a causal correlation between the traumatic event and the meningeal infection, this may result to be extremely complex. In fact, as described in the scientific literature, the time-lapse between trauma and clinical signs of infectious disease result can be extremely variable, from a minimum of a few hours to a maximum time of several years [96][97][98][99].…”

“…It is also possible to perform immunohistochemical studies for the post-mortem diagnosis of sepsis related to meningitis [97,98]. For the pathologist, the historical immunohistochemical markers used (β-APP, GFAP) will continue to play an important role in the diagnostic evaluation process; the best understanding of the molecular mechanisms involved in the pathogenesis of the resulting damage to a TBI, however, as well as the understanding of oxidative stress leading to apoptosis, will assume greater importance, as the potential to allow for a more precise diagnosis in time compared with classic markers (Figure 6).…”