Apoptosis of Circulating Heterophils; Implications for the Interpretation of the Heterophil/Lymphocyte Ratio
Paul F. Cotter
Cotter Laboratory, Arlington, MA 02476, USA
The aim is to demonstrate a variety of apoptotic heterophils (equivalents of mammalian neutrophils) occurring in hemograms of 50 apparently healthy pullets housed in cages. These atypical cells are found in blood with normal total white cell levels (TWBC, ~20K) and in those ranging up to 100(K) a leukocytosis/leukemoid reaction level. Conversely heterophil/lymphocyte (H/L) ratios in all hens ranged between 0.14 – 0.50 (homeostasis). The Arneth index (a heterophil age measure) of 1.8 computed using only intact heterophils indicated a “left-shift”, suggesting inflammation even in the context of a normal hemogram.
The results: atypical heterophils with condensed (pyknotic) and fragmented nuclei (karyorrhexis), ruffled cytoplasmic membranes (zeiosis), apoptotic body formation, and other characteristics of apoptosis circulated in the blood of the study hens. Highly unusual cells as a monocyte containing a phagocytosed apoptotic body composed of heterophil granules, and a Mott cell (atypical plasmacyte) were also found.
More importantly, heterophils displaying thin, swollen and externalized nuclei suggestive of an unusual form of karyolysis were present. These cells were often seen in the company of free or RBC associated bacteria and fungi. There were also two examples of bacteria phagocytosed by apoptotic cells.
Other types of apoptotic cells were in 16/50 (32%) of hens from the study sample. These included small and medium size lymphocytes, monocytes, and metamyelocytes. Frank evidence of bacteremia (5/50, 10%) fungemia (4/50, 8%) and both (1/50, 2%) were detected. This suggests a relation between hematological atypia and the presence of circulating microorganisms possibly mediated through the release of toxins. Atypia of the circulation are sentinels, an alert to investigators or clinicians who are interested in the relation between the composition of blood and stress measurement or disease.
Conclusions: these observations apply to apparent morphologic plasticity of the heterophil, its role in the innate immune system, and its use in determining stress. In the cases described here the initial computation of the H/L ratios suggested the absence of stress. Moreover, this occurred in the context of either a normal or a high TWBC. However, heterophil age indicated a left-shift; a population predominated by young cells. This situation occurs when there is a demand to replace cells that have left the circulation either due to inflamed tissues or to death while circulating. Therefore, circulating apoptotic cells suggest stress even when the H/L is low and the TWBC is normal.
DOI: 10.29245/2578-3009/2021/4.1222 View / Download PdfEpitope-based Multi-variant SARS-Cov-2 Vaccine Design: Shared Epitopes Among the Natural SARS-Cov-2 Spike Glycoprotein and 5 of its Variants (D614G, α, β, γ, δ) with High in Silico Binding Affinity to Human Leukocyte Antigen (HLA) Class II Molecules
DOI: 10.29245/2578-3009/2021/4.1223 View / Download PdfVagaries of the Host Response to Chronic Hepatitis B Virus Infection: What is the Ultimate Outcome of So-called "Asymptomatic HBV Carriers" Observed Over Several Decades?
Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease.
Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver.
Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.
DOI: 10.29245/2578-3009/2021/4.1224 View / Download Pdf