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Pulmonary arterial hypertension (PAH) from autopsy study: T-cells, B-cells and mastocytes detection as morphological evidence of immunologically mediated pathogenesis.
Mansueto, Gelsomina; Di Napoli, Mario; Campobasso, Carlo Pietro; Slevin, Mark.
  • Mansueto G; Department of Advanced Medical and SurgicalSciences, University of Campania "Luigi Vanvitelli"; Clinical Department of Laboratory Services and Public Health, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy; Clinical Department of Laboratory Services and Public Health, University of Ca
  • Di Napoli M; Neurological Service, SS Annunziata Hospital, Viale Mazzini 100 Sulmona, 67039 L'Aquila, Italy. Electronic address: mariodinapoli@katamail.com.
  • Campobasso CP; Clinical Department of Laboratory Services and Public Health, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy; Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. Electronic address: carlopietro.campobasso@unicampania.it.
  • Slevin M; Departmentof Life Sciences Manchester Metropolitan University, Chester Street, Manchester M1 5GD, United Kingdom; University of Medicine and Pharmacy, Scienceand Technology, W1G 7ET Târgu Mures, Romania. Electronic address: m.a.slevin@mmu.ac.uk.
Pathol Res Pract ; 225: 153552, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1440296
ABSTRACT

BACKGROUND:

Pulmonary arterial hypertension (PAH) is characterized by severe vascular remodelling, resulting in increased pulmonary vascular resistance with cardiac hypertrophy and heart failure. However, the diagnosis of PAH is often inaccurate. Many cases of PAH are incorrectly diagnosed or missed, and they are often associated with death. The aim of this study was to verify the morphological and histological criteria of fatal cases of PAH and evaluate the lymphocytic populations associated to lesions with reactive neo-angiogenesis.

METHODS:

Pulmonary lung sections from 10 cases of sudden unexpected death (SUD) in the absence of previously diagnosed diseases and in an apparent state of well-being, with final histological post autopsy diagnosis of PAH were collected. The pathological findings were compared using ten controls from non-pathological lung from deaths from other causes. The autopsies included 4 males (40%) and 6 females (60%) with an average age of 52.1 ± 10.1 years. Sections stained with hematoxylin and eosin (H&E) were revised for a morphological diagnosis. Subsequently, serial sections were performed and stained with immunohistochemistry for anti-CD20 (B-lymphocytes), anti-CD3 (T-lymphocytes), anti-CD4 (T-helper lumphocytes), anti-CD8 (T-cytotoxic lymphocytes) and anti-CD117/C-Kit (mast cells/MCs) to detect inflammatory infiltrate and different ratios of cell-type. Statistical analysis was conducted using a paired t-test looking at 100 cells in 3 different tissue samples representative of vascular lesion and 3 different random normal lung parenchyma fields without lesion (from 10 normal control lungs), to identify specific lymphocyte subpopulations in inflammatory infiltrates.

RESULTS:

There was a significant percentage increase of CD20 (p < 0.001), CD8 (p = 0.002), CD4 (p < 0.001), and CD117/C-Kit positive (C-Kit+; p < 0.001) cells mainly detected around wall vessels; while increased MCs positivity and C-Kit+ were observed especially in alveolar septa. In addition, reactive angiomatosis was observed.

CONCLUSIONS:

The inflammatory infiltrate should be included for a correct diagnosis of PAH besides the vascular remodelling. The inflammatory infiltrate seems to be implicated as a main factor in the pathogenesis. This finding is important to rule out secondary pulmonary hypertension, to identify SUDs of unknown causes and to add new elements to the literature that can explain the immunologically related pathogenesis of PAH.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / T-Lymphocytes / Pulmonary Arterial Hypertension / Lung / Mast Cells Type of study: Experimental Studies / Observational study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Pathol Res Pract Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / T-Lymphocytes / Pulmonary Arterial Hypertension / Lung / Mast Cells Type of study: Experimental Studies / Observational study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Pathol Res Pract Year: 2021 Document Type: Article