Hypoparathyroidism, Retardation, and Dysmorphism Syndrome: Impaired Early Growth and Increased Susceptibility to Severe Infections Due to Hyposplenism and Impaired Polymorphonuclear Cell Functions

AbstractCOVID-19 can cause acute respiratory distress syndrome (ARDS), leading to death in a significant number of individuals. Evidence of a strong role of the innate immune system is accumulating, but the precise cells and mechanism involved remain unclear. In this study, we investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 patients. Eighty-four consecutive patients were included, 44 of which were in intensive care units (ICU). We performed an in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, myeloid cell functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Resulting parameters were linked to disease severity and prognosis. Both ICU and non-ICU patients had circulating neutrophils and monocytes with an activated phenotype, as well as elevated concentrations of soluble activation markers (calprotectin, myeloperoxidase, neutrophil extracellular traps, MMP9, sCD14) in their plasma. ICU patients were characterized by increased CD10low CD13low immature neutrophils, LOX-1+ and CCR5+ immunosuppressive neutrophils, and HLA-DRlow CD14low downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity and poor outcome. Moreover, neutrophils and monocytes of ICU patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Our study reveals a marked dysregulation of innate immunity in COVID-19 patients, which was correlated with severity and prognosis. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.One Sentence SummaryOur study reveals a marked dysregulation of innate immunity in COVID-19 patients, which correlates with severity and prognosis.

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Evaluation of the Polymorphonuclear Cell Functions of Bottlenose Dolphins

Journal of Veterinary Medical Science ◽

10.1292/jvms.65.727 ◽

2003 ◽

Vol 65 (6) ◽

pp. 727-729 ◽

Cited By ~ 16

Author(s):

Katsura NODA ◽

Mika AOKI ◽

Hideo AKIYOSHI ◽

Hiroshi ASAKI ◽

Terumasa SHIMADA ◽

...

Keyword(s):

Bottlenose Dolphins ◽

Polymorphonuclear Cell ◽

Cell Functions

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Effect of glucose concentration, osmolality, and sterilization process of peritoneal dialysis fluids on cytokine production by peripheral blood mononuclear cells and polymorphonuclear cell functions in vitro

American Journal of Kidney Diseases ◽

10.1053/ajkd.1998.v31.pm9469498 ◽

1998 ◽

Vol 31 (2) ◽

pp. 273-282 ◽

Cited By ~ 45

Author(s):

M Cendoroglo ◽

S Sundaram ◽

BL Jaber ◽

BJ Pereira

Keyword(s):

Mononuclear Cells ◽

Cytokine Production ◽

Polymorphonuclear Cell ◽

Peripheral Blood Mononuclear ◽

Cell Functions ◽

Blood Mononuclear Cells ◽

Sterilization Process ◽

Effect Of Glucose ◽

Dialysis Fluids

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Oral vitamin C treatment increases polymorphonuclear cell functions in type 2 diabetes mellitus patients with poor glycemic control

Nutrition Research ◽

10.1016/j.nutres.2020.05.010 ◽

2020 ◽

Vol 79 ◽

pp. 50-59

Author(s):

Nisa Chuangchot ◽

Chongchira Boonthongkaew ◽

Wisitsak Phoksawat ◽

Amonrat Jumnainsong ◽

Chanvit Leelayuwat ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Vitamin C ◽

Poor Glycemic Control ◽

Polymorphonuclear Cell ◽

Oral Vitamin ◽

Cell Functions

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Combinatorial CAR design improves target restriction

10.1101/2020.10.09.333724 ◽

2020 ◽

Author(s):

Hakan Köksal ◽

Pierre Dillard ◽

Asta Juzeniene ◽

Gunnar Kvalheim ◽

Erlend B. Smeland ◽

...

Keyword(s):

B Lymphocyte ◽

Clinical Results ◽

Target Specificity ◽

Car T Cells ◽

Serum Igg ◽

Car T ◽

B Cell Leukemia ◽

Severe Infections ◽

B Lineage ◽

Increased Susceptibility

AbstractCAR T cells targeting the B-lymphocyte antigen CD19 have led to remarkable clinical results in B-cell leukemia and lymphoma, but eliminate all B-lineage cells, leading to increased susceptibility to severe infections. As malignant B cells will express either immunoglobulin (Ig) light chain κ or λ, we designed a second-generation CAR targeting Igκ, IGK CAR. This construct demonstrated high target specificity, but displayed reduced efficacy in the presence of serum IgG. Since CD19 CAR is insensitive to serum IgG, we designed various combinatorial CAR constructs in order to maintain the CD19 CAR T cell efficacy, but with IGK CAR target selectivity. The Kz-19BB design, combining CD19 CAR containing a 4-1BB co-stimulatory domain with an IGK CAR containing a CD3zeta stimulatory domain, maintained the target specificity of IgK CAR and was resistant to the presence of soluble IgG. Our results demonstrate that a combinatorial CAR approach can improve target selectivity and efficacy.

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Depressed polymorphonuclear cell functions in periparturient cows that develop postpartum reproductive diseases

Veterinary Research Communications ◽

10.1007/s11259-017-9691-z ◽

2017 ◽

Vol 41 (3) ◽

pp. 201-209 ◽

Cited By ~ 3

Author(s):

Rafiqul Islam ◽

Harendra Kumar ◽

Gyanendra Singh ◽

Binsila B. Krishnan ◽

Sahadeb Dey

Keyword(s):

Polymorphonuclear Cell ◽

Cell Functions ◽

Periparturient Cows

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Total C4B Deficiency Due to Gene Deletion and Gene Conversion in a Patient with Severe Infections

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.2.195-201.2003 ◽

2003 ◽

Vol 10 (2) ◽

pp. 195-201 ◽

Cited By ~ 5

Author(s):

Taina Jaatinen ◽

Meri Lahti ◽

Olli Ruuskanen ◽

Riikka Kinos ◽

Lennart Truedsson ◽

...

Keyword(s):

Gene Deletion ◽

Mutation Screening ◽

Long Term Effects ◽

Chronic Infections ◽

Plasma Therapy ◽

Classical Complement Pathway ◽

New Information ◽

Severe Infections ◽

Mannan Binding Lectin ◽

Increased Susceptibility

ABSTRACT Deficiencies of the early components of the classical complement pathway impair the actions of innate and humoral immunity and may lead to increased susceptibility to infections. We have studied the genetic basis of total C4B deficiency in a Finnish patient with recurrent meningitis, chronic fistulas and abscesses. The maternal chromosome carried a four-gene deletion including the C4B gene, and a conversion from C4B to C4A gene was found on the paternal chromosome resulting in complete deficiency of C4B. In the converted C4A gene, mutation screening did not reveal any amino acid changes or prominent mutations, yet a large number of nucleotide variations were found. Further, the patient was heterozygous for structural deficiency of mannan binding lectin (MBL) associating with medium levels of serum MBL. Our data provides new information on the genetic instability of the C4 gene region, and on the association of homozygous C4B deficiency and variant MBL genotype with increased susceptibility to recurrent and chronic infections. Importantly, plasma therapy induced a prompt clinical cure with long-term effects.

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Combinatorial CAR design improves target restriction

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.016234 ◽

2020 ◽

pp. jbc.RA120.016234

Author(s):

Hakan Köksal ◽

Pierre Dillard ◽

Asta Juzeniene ◽

Gunnar Kvalheim ◽

Erlend Bremertun Smeland ◽

...

Keyword(s):

B Lymphocyte ◽

Clinical Results ◽

Target Specificity ◽

Car T Cells ◽

Serum Igg ◽

Car T ◽

B Cell Leukemia ◽

Severe Infections ◽

B Lineage ◽

Increased Susceptibility

CAR T cells targeting the B-lymphocyte antigen CD19 have led to remarkable clinical results in B-cell leukemia and lymphoma, but eliminate all B-lineage cells, leading to increased susceptibility to severe infections. As malignant B cells will express either immunoglobulin (Ig) light chain κ or λ, we designed a second-generation CAR targeting Igκ, IGK CAR. This construct demonstrated high target specificity, but displayed reduced efficacy in the presence of serum IgG. Since CD19 CAR is insensitive to serum IgG, we designed various combinatorial CAR constructs in order to maintain the CD19 CAR T cell efficacy, but with IGK CAR target selectivity. The Kz-19BB design, combining CD19 CAR containing a 4-1BB co-stimulatory domain with an IGK CAR containing a CD3zeta stimulatory domain, maintained the target specificity of IgK CAR and was resistant to the presence of sIgG. Our results demonstrate that a combinatorial CAR approach can improve target selectivity and efficacy.

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