Immune Cells Profiles in the Different Sites of COVID-19-Affected Lung Lobes in a Single Patient

Iwabuchi, Sadahiro; Miyamoto, Kyohei; Hatai, Mayuko; Mikasa, Yurina; Katsuda, Masahiro; Murata, Shin‐ichi; Kondo, Toshikazu; Yamaue, Hiroki; Hashimoto, Shinichi

doi:10.3389/fmed.2022.841170

Cited by 3 publications

(5 citation statements)

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“…Several BCR IgH and IgK chains have been detected in the upper lung lobe, following signs of mild inflammation and SARS-CoV-2 detection (15). IGHV1-69, IGHV3-23, IGKV2-28, and IGKV3-20, which were the most frequently detected IgH chains (Figure 1C), were compared with the BCR repertoires associated with COVID-19 reported in other studies.…”

Section: Discussionmentioning

confidence: 80%

“…Although the types of (D) and (J) of CDR3 were different, the heavy chains, IGHV1-69 and IGHV3-23, were detected in 9.2% and 12.5% of the total, respectively, whereas the light chains, IGKV2-28 and IGKV3-20, accounted for 31.3% and 23.7% of the total, respectively (Supplementary Data Sheet 2). In 25%-30% of the LUL regions, we observed mildly thickened alveolar walls and hyaline membrane formation with mild inflammation and diffused alveolar damage, whereas the lower lung lobes showed fibrous and thickened alveolar walls with severe inflammation (15). Therefore, it was difficult to identify multiple IgH genes from the RLL samples, as the sequencing library was excessively fragmented (Supplementary Figure 1); therefore, only two IgH genes and 18 IgK chain genes were identified in the RLL tissues (Supplementary Data Sheet 2).…”

Section: Identified Specific B Cell Repertoire In Lower Lung Lobesmentioning

confidence: 78%

“…We had provided an overview of RNA expression, immune cell populations, cytokine expression, and histopathological characteristics of the formalin fixation and paraffin-embedding (FFPE) lung lobes of a patient with COVID-19 (15,16), and the comprehensive analysis indicates the distribution of SARS-CoV-2 and the cellular and molecular differences among mild-to-severely inflamed microenvironment in different lung lobes. We further found that the severely inflamed lung lobes highly express aquaporin-3 (AQP3)-positive basal-like cells and alveolar type II cells, which proliferate abnormally to fill the alveolar space and stromal tissue that collapses upon SARA-CoV-2 infection (15). The B-cells and plasma cells existed in the inflamed lung lobes; therefore, we hypothesized the presence of antibodies with neutralizing activity against SARS-CoV-2 more in the lung lobes.…”

Section: Introductionmentioning

confidence: 99%

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B cell receptor repertoire analysis from autopsy samples of COVID-19 patients

Iwabuchi

Tsukahara²,

Okayama³

et al. 2023

Front. Immunol.

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Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being developed world over. We investigated the possibility of producing artificial antibodies from the formalin fixation and paraffin-embedding (FFPE) lung lobes of a patient who died by coronavirus disease 2019 (COVID-19). The B-cell receptors repertoire in the lung tissue where SARS-CoV-2 was detected were considered to have highly sensitive virus-neutralizing activity, and artificial antibodies were produced by combining the most frequently detected heavy and light chains. Some neutralizing effects against the SARS-CoV-2 were observed, and mixing two different artificial antibodies had a higher tendency to suppress the virus. The neutralizing effects were similar to the immunoglobulin G obtained from healthy donors who had received a COVID-19 mRNA vaccine. Therefore, the use of FFPE lung tissue, which preserves the condition of direct virus sensitization, to generate artificial antibodies may be useful against future unknown infectious diseases.

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Section: Discussionmentioning

confidence: 80%

Section: Identified Specific B Cell Repertoire In Lower Lung Lobesmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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B cell receptor repertoire analysis from autopsy samples of COVID-19 patients

Iwabuchi

Tsukahara²,

Okayama³

et al. 2023

Front. Immunol.

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“…Furthermore, the expression pattern of the identified gene CSMD1 in COVID-19 shows important similarities to basal cell-related carcinomas. Iwabuchi et al (2022) While CSMD1 might be associated with insulin sensitivity and lipid levels in type 2 diabetes patients, this gene may also have an important impact on long-term elevated HbA1c levels. ( Goswami et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis

Bennett

et al. 2022

Front. Genet.

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Recent studies have shown that, compared with healthy individuals, patients with type 2 diabetes (T2D) suffer a higher severity and mortality of COVID-19. When infected with this retrovirus, patients with T2D are more likely to face severe complications from cytokine storms and be admitted to high-dependency or intensive care units. Some COVID-19 patients are known to suffer from various forms of acute respiratory distress syndrome and have a higher mortality risk due to extreme activation of inflammatory cascades. Using a conditional false discovery rate statistical framework, an independent genome-wide association study data on individuals presenting with T2D (N = 62,892) and COVID-19 (N = 38,984) were analysed. Genome-wide association study data from 2,343,084 participants were analysed and a significant positive genetic correlation between T2D and COVID-19 was observed (T2D: r for genetic = 0.1511, p-value = 0.01). Overall, 2 SNPs (rs505922 and rs3924604) shared in common between T2D and COVID-19 were identified. Functional analyses indicated that the overlapping loci annotated into the ABO and NUS1 genes might be implicated in several key metabolic pathways. A pathway association analysis identified two common pathways within T2D and COVID-19 pathogenesis, including chemokines and their respective receptors. The gene identified from the pathway analysis (CCR2) was also found to be highly expressed in blood tissue via the GTEx database. To conclude, this study reveals that certain chemokines and their receptors, which are directly involved in the genesis of cytokine storms, may lead to exacerbated hyperinflammation in T2D patients infected by COVID-19.

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“…AQP3 expression can be found in various parts of the intestine, regulates the proliferation and migration of intestinal epithelial cells, and is responsible for glycerol and hydrogen peroxide transport [13]. It is expressed and also has a direct function in immune cells [11,14,15]. The role of AQP3 described in immune systems is predominantly its function in T-cells [16,17].…”

Section: Introductionmentioning

confidence: 99%

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion

Ziehe,

Marko,

Thon

et al. 2024

IJMS

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Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and expression of aquaporin-3 (AQP3) and correlated these measurements with the survival of sepsis patients. Accordingly, we collected blood samples on several days (plus clinical data) from 265 sepsis patients who stayed in different ICUs in Germany. Serum plasma, DNA, and RNA were then separated to detect the promotor genotypes of AQP3 mRNA expression of AQP3 and several cytokines. The results showed that the homozygote CC genotype exhibited a significant decrease in 30-day survival (38.9%) compared to the CT (66.15%) and TT genotypes (76.3%) (p = 0.003). Moreover, AQP3 mRNA expression was significantly higher and nearly doubled in the CC compared to the CT (p = 0.0044) and TT genotypes (p = 0.018) on the day of study inclusion. This was accompanied by an increased IL-33 concentration in the CC genotype (day 0: p = 0.0026 and day 3: p = 0.008). In summary, the C allele of the AQP3 polymorphism (rs17553719) shows an association with increased AQP3 expression and IL-33 concentration accompanied by decreased survival in patients with sepsis.

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Immune Cells Profiles in the Different Sites of COVID-19-Affected Lung Lobes in a Single Patient

Cited by 3 publications

References 50 publications

B cell receptor repertoire analysis from autopsy samples of COVID-19 patients

B cell receptor repertoire analysis from autopsy samples of COVID-19 patients

Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion

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