| 1. |
- Topping, Louise M., et al.
(författare)
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Standardization of Antigen-Emulsion Preparations for the Induction of Autoimmune Disease Models
- 2022
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Ingår i: Frontiers in Immunology. - Stockholm : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune murine disease models are vital tools for identifying novel targets and finding better treatments for human diseases. Complete Freund’s adjuvant is commonly used to induce disease in autoimmune models, and the quality of the adjuvant/autoantigen emulsion is of critical importance in determining reproducibility. We have established an emulsification method using a standard homogenizer and specially designed receptacle. Emulsions are easy to prepare, form stable and uniform water-in-oil particles, are faster to make than the traditional syringe method, use less material and are designed to fill syringes with ease. In the present study, we have validated the emulsions for induction of experimental autoimmune encephalitis, collagen II induced arthritis, antigen induced arthritis, and delayed type hypersensitivity models. These models were induced consistently and reproducibly and, in some cases, the new method outperformed the traditional method. The method described herein is simple, cost-effective and will reduce variability, thereby requiring fewer animals for in vivo research involving animal models of autoimmune disease and in vaccine development.
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| 2. |
- Aartse, A, et al.
(författare)
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Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1026951-
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and dynamics of the strain-specific hemagglutinin (HA) head- and stem-directed antibody responses are directly after primary influenza virus infection. Here, sera of twelve H1N1pdm2009 influenza virus-infected cynomolgus macaques were evaluated for HA-head and HA-stem domain antibody responses. We observed an early induction of HA-stem antibody responses, which was already decreased by day 56. In contrast, responses against the HA-head domain were low early after infection and increased at later timepoint. The HA-specific B cell repertoires in each animal showed diverse VH-gene usage with preferred VH-gene and JH-gene family usage for HA-head or HA-stem B cells but a highly diverse allelic variation within the VH-usage. HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels relative to HA-stem B cells. In conclusion, our data suggest that HA-stem antibodies are the first to react to the infection while HA-head antibodies show a delayed response, but a greater propensity to enter the germinal center and undergo affinity maturation.
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| 3. |
- Abolhassani, H, et al.
(författare)
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Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1032358-
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Tidskriftsartikel (refereegranskat)abstract
- The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.
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| 4. |
- Abolhassani, H, et al.
(författare)
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Hallmarks of Cancers: Primary Antibody Deficiency Versus Other Inborn Errors of Immunity
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 720025-
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Tidskriftsartikel (refereegranskat)abstract
- Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected patients manifest a frequent and early incidence of malignancies, mainly lymphoma and leukemia. Primary antibody deficiency (PAD) is the most common form of IEI with the highest proportion of malignant cases. In this review, we aimed to compare the oncologic hallmarks and the molecular defects underlying PAD with other IEI entities to dissect the impact of avoiding immune destruction, genome instability, and mutation, enabling replicative immortality, tumor-promoting inflammation, resisting cell death, sustaining proliferative signaling, evading growth suppressors, deregulating cellular energetics, inducing angiogenesis, and activating invasion and metastasis in these groups of patients. Moreover, some of the most promising approaches that could be clinically tested in both PAD and IEI patients were discussed.
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| 5. |
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| 6. |
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| 7. |
- Adler, Anna, et al.
(författare)
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A Robust Method to Store Complement C3 With Superior Ability to Maintain the Native Structure and Function of the Protein
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Complement components have a reputation to be very labile. One of the reasons for this is the spontaneous hydrolysis of the internal thioester that is found in both C3 and C4 (but not in C5). Despite the fact that approximate to 20,000 papers have been published on human C3 there is still no reliable method to store the protein without generating C3(H2O), a fact that may have affected studies of the conformation and function of C3, including recent studies on intracellular C3(H2O). The aim of this work was to define the conditions for storage of native C3 and to introduce a robust method that makes C3 almost resistant to the generation of C3(H2O). Here, we precipitated native C3 at the isoelectric point in low ionic strength buffer before freezing the protein at -80 degrees C. The formation of C3(H2O) was determined using cation exchange chromatography and the hemolytic activity of the different C3 preparations was determined using a hemolytic assay for the classical pathway. We show that freezing native C3 in the precipitated form is the best method to avoid loss of function and generation of C3(H2O). By contrast, the most efficient way to consistently generate C3(H2O) was to incubate native C3 in a buffer at pH 11.0. We conclude that we have defined the optimal storage conditions for storing and maintaining the function of native C3 without generating C3(H2O) and also the conditions for consistently generating C3(H2O).
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| 8. |
- Ahlberg, Emelie, et al.
(författare)
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Breast milk microRNAs : Potential players in oral tolerance development
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development.
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| 9. |
- Ajibola Omotesho, Quadri, et al.
(författare)
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Epigenetic targets to enhance antitumor immune response through the induction of tertiary lymphoid structures
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15
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Forskningsöversikt (refereegranskat)abstract
- Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates found in sites of chronic inflammation such as tumors and autoimmune diseases. The discovery that TLS formation at tumor sites correlated with good patient prognosis has triggered extensive research into various techniques to induce their formation at the tumor microenvironment (TME). One strategy is the exogenous induction of specific cytokines and chemokine expression in murine models. However, applying such systemic chemokine expression can result in significant toxicity and damage to healthy tissues. Also, the TLS formed from exogenous chemokine induction is heterogeneous and different from the ones associated with favorable prognosis. Therefore, there is a need to optimize additional approaches like immune cell engineering with lentiviral transduction to improve the TLS formation in vivo. Similarly, the genetic and epigenetic regulation of the different phases of TLS neogenesis are still unknown. Understanding these molecular regulations could help identify novel targets to induce tissue-specific TLS in the TME. This review offers a unique insight into the molecular checkpoints of the different stages and mechanisms involved in TLS formation. This review also highlights potential epigenetic targets to induce TLS neogenesis. The review further explores epigenetic therapies (epi-therapy) and ongoing clinical trials using epi-therapy in cancers. In addition, it builds upon the current knowledge of tools to generate TLS and TLS phenotyping biomarkers with predictive and prognostic clinical potential.
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