scholarly journals Persistent Activation of Innate Immunity in Patients with Primary Antibody Deficiencies

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Gerasimina Tsinti ◽  
Demosthenes Makris ◽  
Anastasios E. Germenis ◽  
Matthaios Speletas
Keyword(s):  
Innate Immunity ◽  
Cell Activation ◽  
Immune Cell ◽  
Primary Antibody ◽  
Favorable Effect ◽  
Polymorphonuclear Cells ◽  
Replacement Treatment ◽  
Primary Antibody Deficiencies ◽  
Immunoglobulin Replacement ◽  
Clinical Conditions

Primary antibody deficiencies (PAD) represent a heterogeneous group of disorders, with common variable immunodeficiency being the most common with clinical significance. The main phenotypic defect resides in the inability of B cells to produce antibodies, and the cornerstone of therapy is immunoglobulin replacement treatment in order to fight infections. However, the management of the other inflammatory manifestations is inadequate, reinforcing the hypothesis that a complex genetic background affecting additional cell populations, such as polymorphonuclear cells (PMN) and monocytes, influences the expression of the clinical phenotype of the disease. In this study, we investigated by flow cytometry in different conditions (resting state, and after isolation and incubation, with and without stimuli) the expression pattern of several markers on PMN and monocytes, indicative of their maturation, capacity for chemotaxis, adhesion, opsonization, migration, and phagocytosis in 25 PAD patients, 12 healthy blood donors, and 4 septic patients. In this context, we also analyzed patients before and after the initiation of replacement treatment, as well as an untreated patient in different clinical conditions. Interestingly, we observed that PAD patients exhibit a chronic activation status of the innate immunity compartment, along with several differences in the expression of activation, maturation, and adhesion markers, with respect to different clinical conditions. Moreover, immunoglobulin replacement treatment had a favorable effect on PMN, as it was expressed by a more mature and less activated phenotype on basal state cells, and an enhanced activation capacity after LPS exposure. Thus, we conclude that PAD patients display a persistent innate immune cell activation, which is probably associated with the chronic inflammatory stress, usually observed in these disorders.

scholarly journals SIAE Rare Variants in Juvenile Idiopathic Arthritis and Primary Antibody Deficiencies

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Eirini Sevdali ◽  
Elena Tsitsami ◽  
Maria Tsinti ◽  
Evangelia Farmaki ◽  
Efimia Papadopoulou-Alataki ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Sialic Acid ◽  
Cell Activation ◽  
Rare Variants ◽  
Primary Antibody ◽  
Healthy Children ◽  
B Cell Activation ◽  
Loss Of Function ◽  
Primary Antibody Deficiencies ◽  
Sialic Acid Binding

Sialic acid acetylesterase (SIAE) deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA), yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA) and autoimmune oligo/polyarticular (aJIA), and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs), the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs. A cohort of 69 patients with JIA, 117 healthy children, 54 patients, and family members with PADs were enrolled in the study. Three novel SIAE variants (p.Q343P, p.Y495X, and c.1320+33T>C) were found only in patients with aJIA but interestingly also in their healthy relatives without autoimmunity, while none of PAD patients or their relatives carried SIAE defects. Our results show that SIAE rare variants are not causative of autoimmunity as single defects.

scholarly journals Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Kang ◽  
Marjan Nasr ◽  
Yiru Guo ◽  
Shizuka Uchida ◽  
Tyler Weirick ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Innate Immunity ◽  
Mechanism Of Action ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Mesenchymal Cell ◽  
Cell Types

Abstract Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration—suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably linked to wound healing/remodeling in the ischemically injured heart, the reparative actions of CMCs may be attributed to their immunoregulatory properties. The current study evaluated the consequences of CMC administration on post myocardial infarction (MI) immune responses in vivo and paracrine-mediated immune cell function in vitro. CMC administration preferentially elicited the recruitment of cell types associated with innate immunity (e.g., monocytes/macrophages and neutrophils). CMC paracrine signaling assays revealed enhancement in innate immune cell chemoattraction, survival, and phagocytosis, and diminished pro-inflammatory immune cell activation; data that identifies and catalogues fundamental immunomodulatory properties of CMCs, which have broad implications regarding the mechanism of action of CMCs in cardiac repair.

ENT manifestations in Iranian patients with primary antibody deficiencies

2008 ◽  
Vol 122 (4) ◽  
pp. 409-413 ◽  
Author(s):  
A Aghamohammadi ◽  
K Moazzami ◽  
N Rezaei ◽  
A Karimi ◽  
M Movahedi ◽  
...  
Keyword(s):  
Otitis Media ◽  
Antibody Deficiency ◽  
Primary Antibody ◽  
Demographic Information ◽  
Primary Antibody Deficiency ◽  
Medical Problems ◽  
Primary Antibody Deficiencies ◽  
Immunoglobulin Replacement ◽  
Medical Histories ◽  
Iranian Patients

AbstractObjective:One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications.Method:Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment.Results:Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011).Conclusion:ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

scholarly journals The Chemokine CCL6 Promotes Innate Immunity via Immune Cell Activation and Recruitment

2007 ◽  
Vol 179 (8) ◽  
pp. 5474-5482 ◽  
Author(s):  
Ana L. Coelho ◽  
Matthew A. Schaller ◽  
Claudia F. Benjamim ◽  
Amos Z. Orlofsky ◽  
Cory M. Hogaboam ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cell Activation ◽  
Immune Cell ◽  
Immune Cell Activation

Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs

The Lancet ◽  
1995 ◽  
Vol 345 (8946) ◽  
pp. 365-369 ◽  
Author(s):  
A.Gardulf Rn ◽  
L Hammarström ◽  
R Gustafson ◽  
T Nyström ◽  
C.I.Edvard Smith ◽  
...  
Keyword(s):  
Primary Antibody ◽  
Subcutaneous Immunoglobulin ◽  
Primary Antibody Deficiencies ◽  
Immunoglobulin Replacement

scholarly journals Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies

2009 ◽  
Vol 160 (2) ◽  
pp. 240-245 ◽  
Author(s):  
J. Beauté ◽  
P. Levy ◽  
V. Millet ◽  
M. Debré ◽  
Y. Dudoit ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Primary Antibody ◽  
Primary Antibody Deficiencies ◽  
Immunoglobulin Replacement

scholarly journals Innate Immunity Modulating Impurities and the Immunotoxicity of Nanobiotechnology-Based Drug Products

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7308
Author(s):  
Claire K. Holley ◽  
Marina A. Dobrovolskaia
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Pharmaceutical Products ◽  
Drug Effectiveness ◽  
Host Immune Responses ◽  
Drug Products ◽  
The Many

Innate immunity can be triggered by the presence of microbial antigens and other contaminants inadvertently introduced during the manufacture and purification of bionanopharmaceutical products. Activation of these innate immune responses, including cytokine secretion, complement, and immune cell activation, can result in unexpected and undesirable host immune responses. These innate modulators can also potentially stimulate the activation of adaptive immune responses, including the formation of anti-drug antibodies which can impact drug effectiveness. To prevent induction of these adverse responses, it is important to detect and quantify levels of these innate immunity modulating impurities (IIMIs) that may be present in drug products. However, while it is universally agreed that removal of IIMIs from drug products is crucial for patient safety and to prevent long-term immunogenicity, there is no single assay capable of directly detecting all potential IIMIs or indirectly quantifying downstream biomarkers. Additionally, there is a lack of agreement as to which of the many analytical assays currently employed should be standardized for general IIMI screening. Herein, we review the available literature to highlight cellular and molecular mechanisms underlying IIMI-mediated inflammation and its relevance to the safety and efficacy of pharmaceutical products. We further discuss methodologies used for direct and indirect IIMI identification and quantification.

scholarly journals Metabolic and hematologic changes occurring after rapid intravenous infusion of gammaglobulin in patients with antibody deficiency syndromes

1998 ◽  
Vol 116 (5) ◽  
pp. 1815-1820 ◽  
Author(s):  
Beatriz Tavares Costa-Carvalho ◽  
Marisa Lin ◽  
Dirceu Solé ◽  
Magda Maria Sales Carneiro-Sampaio ◽  
Ricardo Uhr Sorensen ◽  
...  
Keyword(s):  
Side Effects ◽  
Intravenous Infusion ◽  
Infusion Rate ◽  
Pediatric Patients ◽  
Antibody Deficiency ◽  
Primary Antibody ◽  
Rapid Infusion ◽  
Replacement Treatment ◽  
Primary Antibody Deficiencies ◽  
Ivig Preparation

OBJECTIVE: We wished to investigate whether increased IgG infusion rates are associated with metabolic and hematologic changes in pediatric patients with antibody deficiency syndromes. METHODS: We studied 7 patients (2-16 years old) with primary antibody deficiencies who had been on regular IgG replacement treatment, 350-600 mg/kg/dose every 3 weeks with a 3% IVIG preparation, for periods ranging from 6 months to 4 years. Initially, the IgG concentration of IVIG preparations was increased to 6, 9 and 12% in consecutive infusions at a constant IgG infusion rate of 4 mg/kg/min. Subsequently, the infusion rates were increased to 8, 12, and 16 mg/kg/min using the IVIG 12% preparation. RESULTS: Clinically, all patients tolerated increases in IVIG concentrations while the infusion rate was 4 mg/kg/min. However, 3 patients presented side effects when the infusion rate was increased to 8 and 16 mg/kg/min. CONCLUSION: We conclude that metabolic and hematologic sides effects occur with rapid infusion of IVIG even in patients who tolerate the increased infusion rate clinically. The advantages of using high infusion rates have to be re-evaluated.

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