CD4+ T cells migrate from airway to bone marrow after antigen inhalation in rats

BACKGROUND: IL-5-producing T lymphocytes increase in rat bone marrow after inhalational challenge with allergen. OBJECTIVE: To test the hypothesis that T cells migrate from the airways to the marrow, we examined the trafficking of T cells in Brown Norway rats after sensitization and challenge with ovalbumin. METHODS: Purified CD4+ T cells, harvested from cervical lymph nodes of naive and ovalbumin-sensitized donors, were labeled with carboxy fluorescein diacetate succinimidyl ester; 20 x 10(6) cells were placed in the trachea of naive or sensitized recipients under anesthesia, and 18 hours later, animals were challenged with inhaled ovalbumin. Cells were harvested 24 hours later from the bone marrow, bronchoalveolar lavage fluid, lungs, the lung blood pool of cells, lung draining lymph nodes, peripheral blood, and spleen. RESULTS: The number of carboxy fluorescein diacetate succinimidyl ester-positive cells, measured by fluorescence-activated cell sorter, in the bone marrow of ovalbumin sensitized, primed T-cell recipients was higher than either the sham-sensitized, primed T-cell recipients or sham-sensitized, naive T-cell recipients (P < .05). The number of eosinophils in both bone marrow and bronchoalveolar lavage fluid was increased in ovalbumin-sensitized, primed T-cell recipients. The expression of the T-cell chemoattractants eotaxin and IL-16, evaluated by immunohistochemistry, was higher in the bone marrow of ovalbumin-sensitized, primed T-cell recipients. CONCLUSIONS: CD4+ T cells travel from airway to bone marrow after antigen inhalation. The homing of the CD4+ T cells might be facilitated by eotaxin and IL-16 expression in the bone marrow and might contribute to the stimulation of eosinophilopoiesis after airway allergen exposure.     

Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

ABSTRACT: BACKGROUND: Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). METHODS: Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. RESULTS: We found that monocytes from chronic HCV infected treatment-naive (cHCV) but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFalpha, and had increased TNFalpha production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFalpha production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. CONCLUSION: In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate increased miR-155 and TNFalpha production in chronic HCV infection. The positive correlation between serum miR-155 and miR-122 increase in cHCV may be an indicator of inflammation-induced hepatocyte damage.     

T‐cell responses and therapies against SARS‐CoV‐2 infection

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel coronavirus strain. Some studies suggest that COVID‐19 could be an immune‐related disease, and failure of effective immune responses in initial stages of viral infection could contribute to systemic inflammation and tissue damage, leading to worse disease outcomes. T cells can act as a double‐edge sword with both pro‐ and anti‐roles in the progression of COVID‐19. Thus, better understanding of their roles in immune responses to SARS‐CoV‐2 infection is crucial. T cells primarily react to the spike protein on the coronavirus to initiate antiviral immunity; however, T‐cell responses can be suboptimal, impaired or excessive in severe COVID‐19 patients. This review focuses on the multifaceted roles of T cells in COVID‐19 pathogenesis and rationalizes their significance in eliciting appropriate antiviral immune responses in COVID‐19 patients and unexposed individuals. In addition, we summarize the potential therapeutic approaches related to T cells to treat COVID‐19 patients. These include adoptive T‐cell therapies, vaccines activating T‐cell responses, recombinant cytokines, Th1 activators and Th17 blockers, and potential utilization of immune checkpoint inhibitors alone or in combination with anti‐inflammatory drugs to improve antiviral T‐cell responses against SARS‐CoV‐2.     

The role of the computerized tomography scanner in the cross-transmission of carbapenem-resistant Acinetobacter baumannii between hospitalized patients

ObjectiveTo assess the role of the computerized tomography (CT) scanner in cross-transmission of carbapenem-resistant Acinetobacter baumannii between hospitalized patients undergoing CT scan.MethodsA single-centre retrospective observational analysis of inpatients undergoing CT scans. Patient-unique CT scans were defined as ‘index cases’ (patients undergoing CT scan with carbapenem-resistant Acinetobacter baumannii (CRAB) colonization documented during the previous 60 days), ‘incident cases’ (patients found colonized with CRAB within 14 days following CT scan), and ‘negative cases’ (negative for CRAB before and after CT scan). CRAB acquisition was analysed by time interval between CT scan and CT scan of the prior index-case patient.ResultsAmongst 73 047 CT scans performed over 5 years, 4834 scans were performed within 12 hours of an index case. CRAB acquisition was detected in 20 patients (incident cases), including 16/2725 (5.8/1000 scans) who underwent CT scan within 6 hours of an index-case CT scan and 4/2109 (1.9/1000 scans) who had their CT scan 7–12 hours after the CT scan of an index-case patient (p 0.033, risk ratio 3.1, 95%CI 1.03–9.25). Patient characteristics for the two time periods were similar. While not the only significant predictor of CRAB acquisition (others included age and length of hospital stay prior to the CT scan), the time elapsed from an index case remained a significant predictor for CRAB acquisition on multivariate analysis (OR 0.84, 95%CI 0.74–0.95, p 0.007).ConclusionsPerforming a CT scan within 6 hours of a CT scan performed in a CRAB-positive patient was an independent predictor of CRAB acquisition, approximately tripling the risk. This probably reflects poor infection control practice in the CT suite.     

Fetal mid-thigh soft-tissue thickness: a novel method for fetal weight estimation

Purpose

To derive a novel formula for fetal weight estimation utilizing the linear measurement of mid-thigh soft-tissue thickness (STT).

Methods

300 women, with singleton uncomplicated pregnancy, were included in a prospective cross-sectional study. The study included four consecutive phases: phase (1) validated the original Scioscia’s formula, phase (2) derived a novel modified formula for fetal weight estimation, phase (3) validated the novel modified formula, and phase (4) evaluated the agreement between the modified and original formulae.

Results

A statistically significant correlation was found between actual fetal weight (AFW) and various sonographic biometric measurements including mid-thigh STT (r ² = 0.656, p < 0.001), femur length (FL) (r ² = 0.573, p < 0.001), bi-parietal diameter (BPD) (r ² = 0.250, p < 0.001), abdominal circumference (AC) (r ² = 0.310, p < 0.001), and estimated fetal weight (EFW) using the original Scioscia’s formula (r ² = 0.644, p < 0.001). The modified formula showed a better signed % difference (median = ?0.41 %, IQR ?1.88 to 2.03) than the original formula (median = ?0.51 %, IQR ?2.33 to 2.00). It was noted that, using the original formula, 88.7 % of the sample had absolute error below 5 and 98.3 % of the sample had absolute error below 10 %. On the other hand, using the modified formula, 87.3 % of the sample had absolute error below 5 %, while 97.3 % had absolute error below 10 %. The agreement between the two formulae was moderate as 134 patients out of 150 had similar ranking (κ = 0.57).

Conclusion

Fetal mid-thigh SST is a simple, useful, and easily applicable parameter for fetal weight estimation.     

Mastitis and Immunological Factors in Breast Milk of Lactating Women in Malawi

Although an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P < 0.0007); lysozyme, 266 versus 274 mg/liter (P = 0.55); SLPI, 76 versus 15 μg/liter, (P < 0.0002); IL-8, 339 versus 25 ng/liter (P < 0.0001); and RANTES, 82 versus 3 ng/liter (P < 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.     

Vaccine-associated paralytic poliomyelitis in a patient with MHC class II deficiency.

Vaccine-associated paralytic poliomyelitis (VAPP) is a rare complication of oral polio vaccine. We describe a fatal case of VAPP in an 8-month-old boy with Major Histocompatibility Class II deficiency. The isolated poliovirus was a Sabin type 2-type 1 recombinant that showed 1.4% VP1 divergence from Sabin type 2.     

Lack of C9ORF72 coding mutations supports a gain of function for repeat expansions in amyotrophic lateral sclerosis

Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue.     

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.     

COVID-19 and Heart Transplant: A Case Series and Review of the Literature

Coronavirus disease 2019 (COVID-19) has resulted in many challenges in patient care, especially among high-risk populations such as heart transplant recipients. Patients with heart transplant experience a significantly higher mortality rate with COVID-19 infection, and management is based on extrapolation from clinical trials done on nontransplant patients and from clinical experience. Here we report 4 cases of patients with heart transplant who presented with COVID-19 infection in late 2020. Patients presented with symptoms similar to those seen in the general population. All 4 patients were admitted to the hospital, and they were all treated with dexamethasone. In addition, 2 patients received remdesivir. Immunosuppressive medications were adjusted to maintain adequate levels of immunosuppression but at the same time allow for an adequate immune response against the infection. All patients were discharged alive from the hospital. We then performed a literature review on studies that included heart transplant patients who developed the infection and developed suggestions for a standardized management approach, which we share in this article.