IgA autoantibodies target pulmonary surfactant in patients with severe COVID-19

ABSTRACTComplications affecting the lung are hallmarks of severe coronavirus disease 2019 (COVID-19). While there is evidence for autoimmunity in severe COVID-19, the exact mechanisms remain unknown. Here, we established a prospective observational cohort to study lung specific autoantibodies (auto-Abs). Incubation of plasma from severe COVID-19 patients with healthy human lung tissue revealed the presence of IgA antibodies binding to surfactant-producing pneumocytes. Enzyme-linked immunosorbent assays (ELISA) and protein pull-downs using porcine surfactant confirmed the presence of auto-Abs binding to surfactant proteins in severe COVID-19 patients. Mass spectrometry and ELISAs with recombinant proteins identified IgA auto-Abs that target human surfactant proteins B and C. In line with these findings, lungs of deceased COVID-19 patients showed reduced pulmonary surfactant. Our data suggest that IgA-driven autoimmunity against surfactant may result in disease progression of COVID-19.

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Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS

Analytical Chemistry ◽

10.1021/acs.analchem.0c02815 ◽

2020 ◽

Vol 92 (17) ◽

pp. 12079-12087

Author(s):

Sebastiaan Van Nuffel ◽

Marceau Quatredeniers ◽

Alexander Pirkl ◽

Julia Zakel ◽

Jean-Pierre Le Caer ◽

...

Keyword(s):

Mass Spectrometry ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Lung Tissue ◽

Multimodal Imaging ◽

Human Lung ◽

Imaging Mass Spectrometry ◽

Human Lung Tissue ◽

Tof Sims ◽

Pulmonary Arterial

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Surfactant proteins A and D: role in the pathogenesis of community-acquired pneumonia and possible predictive perspectives

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.03.000275 ◽

2020 ◽

Vol 92 (3) ◽

pp. 109-115

Author(s):

O. S. Kharlamovа ◽

K. Yu. Nikolaev ◽

Yu. I. Ragino ◽

M. I. Voevoda

Keyword(s):

Pulmonary Surfactant ◽

Causes Of Death ◽

Human Lung ◽

Serum Levels ◽

Biological Properties ◽

Community Acquired Pneumonia ◽

Surfactant Proteins ◽

Immunomodulatory Activity ◽

Microbial Infection ◽

Life Threatening

Community-acquired pneumonia is one of the most common infectious diseases and remains one of the leading causes of death in this group of diseases. Studies of community-acquired pneumonia are extremely relevant for modern clinical practice. One of the important role in the pathogenesis of bacterial, viral, fungal invasion in the system of a human lung system belongs to the pulmonary surfactant, in particular, its proteins SP-A and SP-D. This article reviews the well-known mechanisms of important biological properties of immunomodulatory activity of the proteins SP-A and SP-D in response to microbial infection in the lungs. The mechanisms of participation of surfactant proteins SP-A and SP-D in the cascade of reactions that lead to severe life-threatening complications in community-acquired pneumonia are considered. The use of serum levels of surfactant proteins SP-A and SP-D can help finding new diagnostic and prognostic approaches in patients with community-acquired pneumonia.

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A novel system for the culture of human lung: lung development and the response to injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1992.263.3.l308 ◽

1992 ◽

Vol 263 (3) ◽

pp. L308-L316

Author(s):

M. T. Hsu ◽

M. Dimaio ◽

O. K. Reiss ◽

D. Ciurea ◽

J. Gil

Keyword(s):

Organ Culture ◽

Pulmonary Surfactant ◽

Human Lung ◽

Lipid Analysis ◽

Calf Serum ◽

Fetal Lung ◽

Type I ◽

Human Lung Tissue ◽

Cell Hyperplasia ◽

Lung Organ Culture

Existing methods of fetal lung organ culture are complicated and require special skills. With the use of a polyester-based plastic sheet, we have developed a simpler human fetal lung organ culture that is viable for 6 wk. This novel method permits the study of growth and differentiation, pulmonary surfactant secretion, and the response of human lung tissue to injury in vitro. Lung tissues, obtained from human fetuses ranging in gestational age from 14 to 18 wk, were cultured on the polyester sheet in Dulbecco's modified Eagle medium supplemented with 15% fetal calf serum and gentamicin. Microscopic study of the fetal lung before culturing revealed round epithelial tubules, lined by glycogen-rich columnar cells and a thick cellular interstitium. After 1 wk in culture, morphological examination showed the development and expansion of alveolar saccules and thinning of the interstitium; type I and II pneumocytes as well as fibroblasts and myofibroblasts were present. Lipid analysis of the tissues, 2 wk after the initiation of the culture, demonstrated a high percentage of dipalmitoyl phosphatidylcholine characteristic of pulmonary surfactant. Treatment of the organ culture with asbestos fibers induced type II cell hyperplasia, increased numbers of collagen fiber bundles within the interstitium, and the accumulation of multi-lamellated surfactant material within the alveolar lumens. We conclude that this organ culture system is suitable for studying lung growth, development, and injury in human tissue.

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HIV-1 Genotypes and Disease Progression Among Chinese Men Who Have Sex with Men: An Observational Cohort Study

SSRN Electronic Journal ◽

10.2139/ssrn.3234880 ◽

2018 ◽

Author(s):

Yuanhao Liang ◽

Zhigang Han ◽

Jingwei Shui ◽

Weibin Cheng ◽

Fei Zhong ◽

...

Keyword(s):

Cohort Study ◽

Disease Progression ◽

Observational Cohort Study ◽

Chinese Men ◽

Observational Cohort ◽

Sex With Men ◽

Hiv 1

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P0741CHRONIC KIDNEY DISEASE PROGRESSION IN A LARGE PREVENTION COHORT IN COLOMBIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0741 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Angela Rivera ◽

Angelito Bernardo ◽

Jasmin Vesga ◽

Izcay Ronderos ◽

Mauricio Sanabria

Keyword(s):

Kidney Disease ◽

Disease Progression ◽

Prevention Program ◽

Reduction Rate ◽

Progression Rate ◽

Ckd Progression ◽

Care Services ◽

Kaplan Meier ◽

Observational Cohort ◽

Kidney Disease Progression

Abstract Background and Aims Chronic kidney disease (CKD) is a syndrome that today has important implications for the health of populations and the economic sustainability of health systems around the world, therefore strategies to slow disease progression are necessary. Aims: To estimate the incidence of renal replacement therapy (RRT) in a cohort of patients included in a CKD secondary prevention program and to describe the decrease of the estimated glomerular filtration rate (eGFR). Method This is a historical, multicenter, observational cohort study in a prevention program between January 1, 2010, and December 31, 2017, with follow-up until December 31, 2018, at the Renal Care Services (RCS) network. Socio-demographic and clinical characteristics of all patients were summarized descriptively. We estimated the incidence of RRT rate with Kaplan Meier analysis. Progression rate to RRT was analyzed by mixed-effects model adjusted for the eGFR reduction rate at 180 days; the model considered the diagnosis of diabetes. Results 7131 patients met the inclusion criteria for data analysis. The mean age was 65 years, 50.5% were female, (Table 1). There were 577 events of RRT with a rate of 2.02 events of RRT per 100 patients-year [95% CI,1.86 to 2.19], characteristics at the RRT initiation are presented in Table 2. At the beginning of the program the eGFR was 45.3 ml / min / 1.73m2 in non-diabetics, and 40.9 3 ml / min / 1.73m2 in diabetics. The CKD progression was - 0.48 ml / min / 1.73m2 per 180 days in diabetics and - 0.20 ml / min / 1.73m2 per 180 days in non-diabetics. The final events of the cohort are presented in Figure 1; the mortality rate was 0.89 events per 100 patients-year [95% CI, 0,79 to 1,01]. Conclusion This population of patients in a CKD prevention program presented a low rate of initiation of dialysis therapy and a slight decrease of eGFR; the diabetic status influences the CKD progression.

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Steady-state kinetics of serum bile acids in healthy human subjects: single and dual isotope techniques using stable isotopes and mass spectrometry.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)38702-2 ◽

1987 ◽

Vol 28 (3) ◽

pp. 238-252

Author(s):

G T Everson

Keyword(s):

Mass Spectrometry ◽

Stable Isotopes ◽

Steady State ◽

Bile Acids ◽

Human Subjects ◽

Healthy Human ◽

Dual Isotope ◽

Steady State Kinetics ◽

Healthy Human Subjects ◽

Kinetics Of

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Mast Cell Heterogeneity in Human Lung Tissue

Clinical Science ◽

10.1042/cs0770297 ◽

1989 ◽

Vol 77 (3) ◽

pp. 297-304 ◽

Cited By ~ 10

Author(s):

F. J. Van Overveld ◽

L. A. M. J. Houben ◽

F. E. M. Schmitz du Moulin ◽

P. L. B. Bruijnzeel ◽

J. A. M. Raaijmakers ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Alcian Blue ◽

Lung Tissue ◽

Human Lung ◽

Immunoglobulin E ◽

Prostaglandin D2 ◽

Leukotriene C4 ◽

Human Lung Tissue ◽

No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

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