{"title":"Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.","authors":"Ingrid Lamminpää, Elena Niccolai, Amedeo Amedei","doi":"10.1111/sji.13405","DOIUrl":"10.1111/sji.13405","url":null,"abstract":"<p><p>In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13405"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rucha Chandwaskar, Rajdeep Dalal, Saurabh Gupta, Aishwarya Sharma, Deepak Parashar, Vivek K Kashyap, Jagdip Singh Sohal, Subhash K Tripathi
{"title":"Dysregulation of T cell response in the pathogenesis of inflammatory bowel disease.","authors":"Rucha Chandwaskar, Rajdeep Dalal, Saurabh Gupta, Aishwarya Sharma, Deepak Parashar, Vivek K Kashyap, Jagdip Singh Sohal, Subhash K Tripathi","doi":"10.1111/sji.13412","DOIUrl":"10.1111/sji.13412","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are gut inflammatory diseases that were earlier prevalent in the Western Hemisphere but now are on the rise in the East, with India standing second highest in the incidence rate in the world. Inflammation in IBD is a cause of dysregulated immune response, wherein helper T (Th) cell subsets and their cytokines play a major role in the pathogenesis of IBD. In addition, gut microbiota, environmental factors such as dietary factors and host genetics influence the outcome and severity of IBD. Dysregulation between effector and regulatory T cells drives gut inflammation, as effector T cells like Th1, Th17 and Th9 subsets Th cell lineages were found to be increased in IBD patients. In this review, we attempted to discuss the role of different Th cell subsets together with other T cells like CD8<sup>+</sup> T cells, NKT and γδT cells in the outcome of gut inflammation in IBD. We also highlighted the potential therapeutic candidates for IBD.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13412"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abel Lissom, Rosette Megnekou, Thibau Flaurant Tchouangueu, Loveline Ngu, Jean Claude Djontu, Herve Fotso Ouambo, Carrie Sanders, Jules Colince Tchadji, Carole Stephanie Sake, Salomon Bonsi Tchuandom, Swapnil Bawage, Arinze Stanley Okoli, Chae Gyu Park, Alain Bopda Waffo, Nchinda Wapimewah Godwin
{"title":"Specific antibody responses to Qβ-displayed Plasmodium falciparum-derived UB05 and MSP3 proteins in mother-neonate couples.","authors":"Abel Lissom, Rosette Megnekou, Thibau Flaurant Tchouangueu, Loveline Ngu, Jean Claude Djontu, Herve Fotso Ouambo, Carrie Sanders, Jules Colince Tchadji, Carole Stephanie Sake, Salomon Bonsi Tchuandom, Swapnil Bawage, Arinze Stanley Okoli, Chae Gyu Park, Alain Bopda Waffo, Nchinda Wapimewah Godwin","doi":"10.1111/sji.13404","DOIUrl":"10.1111/sji.13404","url":null,"abstract":"<p><p>Malaria blood-stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood-stage antigens were well reported in non-pregnant individuals. However, little is still known during placental malaria. To assess the antibody responses specific to Plasmodium falciparum-derived MSP3 and UB05 malaria vaccine candidates in mother-neonate couples, mother's peripheral blood and neonate's cord blood samples were collected at delivery. After malaria diagnostic, plasma levels of IgG and IgG subclass responses specific to UB05, MSP3 and UB05-MSP3 were determined using ELISA. As outcomes, both mothers and neonates had significantly higher IgG responses to UB05 and UB05-MSP3 compared to anti-MSP3 IgG (p < 0.05), irrespective of malaria status. Significant negative correlations were observed between IgG levels specific to the three antigens and parasitaemia (p < 0.01). Anti-UB05 and anti-UB05-MSP3 IgG levels in neonates showed a significant positive correlation with the corresponding mothers' antibodies (r<sub>s</sub> = 0.25 with p = 0.04; r<sub>s</sub> = 0.31 with p = 0.01, respectively). UB05MSP3-specific IgG3 and IgG1 subclass responses were significantly higher than the IgG4 subclass (p < 0.01). The neonates IgG1 and IgG3 levels positively correlated with the corresponding antibody subclasses of mothers. These findings suggest an association between UB05 and UB05-MSP3-specific antibody responses and malaria control during pregnancy. Maternal-foetal transfer of MSP3 and UB05-specific IgG occurs during pregnancy, suggesting the interest in the future malaria vaccination strategies in pregnant women to generate early protective immunity in baby against malaria.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13404"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fengjiao Huang, Lijuan Zhang, Yingying Zhou, Shuiying Zhao, Jiao Wang
{"title":"NrCAM activates the NF-κB signalling pathway by competitively binding to SUMO-1 and promotes Th17 cell differentiation in Graves' disease.","authors":"Fengjiao Huang, Lijuan Zhang, Yingying Zhou, Shuiying Zhao, Jiao Wang","doi":"10.1111/sji.13401","DOIUrl":"10.1111/sji.13401","url":null,"abstract":"<p><p>This study aimed to explore the molecular mechanism of neuronal cell adhesion molecule (NrCAM) by regulating Th17 cell differentiation in the pathogenesis of Graves' disease (GD). Naïve CD4<sup>+</sup> T cells were isolated from peripheral blood mononuclear cells of GD patients and healthy control (HC) subjects. During the differentiation of CD4<sup>+</sup> T cells into Th17 cells, NrCAM level in GD group was improved. Interference with NrCAM in CD4<sup>+</sup> T cells of GD patients decreased the percentage of Th17 cells. NrCAM overexpression in CD4<sup>+</sup> T cells of HC subjects increased the percentage of Th17 cells and upregulated p-IκBα, p50, p65, c-Rel protein expressions, and NF-κB inhibitor BAY11-7082 partially reversed NrCAM effect. NrCAM overexpression promoted the degradation of IκBα, and overexpression of small ubiquitin-related modifier 1 (SUMO-1) inhibited IκBα degradation. NrCAM overexpression reduced IκBα binding to SUMO-1. During Th17 cell differentiation in HC group, NrCAM overexpression increased IL-21 levels and secretion, and IL-21 neutralizing antibody reversed this effect. IL-21 level was decreased after p65 interference in CD4<sup>+</sup> T cells of HC subjects. p65 interacts with IL-21 promoter region. In conclusion, NrCAM binds to SUMO-1 and increases phosphorylation of IκBα, leading to activation of NF-κB pathway, which promotes Th17 cell differentiation.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13401"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can autoantibodies be transferred by immunoglobulin replacement therapy?","authors":"Peter Bergman","doi":"10.1111/sji.13413","DOIUrl":"10.1111/sji.13413","url":null,"abstract":"<p><p></p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"100 5","pages":"e13413"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of autoantibodies associated with intravenous immunoglobulin replacement therapy in children with primary immunodeficiency.","authors":"Murat Özer, Seher Tekeli, Selçuk Doğan, Sema Çetin, Rıdvan Selen, Caner Aytekin","doi":"10.1111/sji.13396","DOIUrl":"10.1111/sji.13396","url":null,"abstract":"<p><p>While it is known that immunoglobulin replacement therapy (IgRT) used in the treatment of primary immunodeficiency disorders (PIDs) can lead to the passive transfer of autoantibodies, there is no data indicating that these antibodies can cause clinical symptoms in patients. This study aimed to investigate the presence of autoantibodies and their clinical correlation in patients diagnosed with PIDs receiving IgRT. Paediatric patients who were diagnosed with PIDs, and administered IgRT at our immunology clinic between 1 January 2012 and 31 December 2021, were included in the study. The medical records of these patients were retrospectively analysed, and autoantibodies were screened. Autoantibody screening was conducted at least once in 48 cases. Among these cases, 29 cases (60.4%) demonstrated positivity for at least one of the autoantibodies screened in the study. Among these cases, 23 tested positive for anti-TPO, 9 for anti-TG and 2 for both anti-TPO and anti-TG. Only two of these patients were confirmed to have Hashimoto's thyroiditis. In 30 cases, autoantibodies related to Celiac disease (CD) were screened, with at least one being positive in five different cases; CD was not confirmed. The results of our study suggest that passive transfer of autoantibodies to patients with IgRT does not cause any significant clinical findings. In addition, in cases of PID, autoantibodies detected in the blood passed to patients with IgRT can lead to misdiagnosis. Screening for autoantibodies in patients with PID undergoing IgRT may not yield accurate results in terms of detecting autoimmune diseases.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13396"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahsa Eshkevar Vakili, Niloofar Mashhadi, Mohammad Reza Ataollahi, Seppo Meri, Dieter Kabelitz, Kurosh Kalantar
{"title":"Hepatitis B vaccine responders show higher frequencies of CD8<sup>+</sup> effector memory and central memory T cells compared to non-responders.","authors":"Mahsa Eshkevar Vakili, Niloofar Mashhadi, Mohammad Reza Ataollahi, Seppo Meri, Dieter Kabelitz, Kurosh Kalantar","doi":"10.1111/sji.13402","DOIUrl":"10.1111/sji.13402","url":null,"abstract":"<p><p>Hepatitis B (HB) infection is a major global health problem. There is limited knowledge about HB vaccination-induced immune memory responses. We compared the frequency of CD8<sup>+</sup> memory T cell subsets between responders (RSs) and non-responders (NRs) to HB vaccination. Blood samples were collected from RSs and NRs. PBMCs were cultured in the presence of Hepatitis B surface antigens (HBsAg) and PHA for 48 h to restimulate CD8<sup>+</sup> memory T cells and T cell memory subsets were detected by flow cytometry using memory cell markers. The frequency of T<sub>EM</sub>, T<sub>CM</sub>, and T<sub>CM</sub> <sup>hi</sup> was significantly higher in responders compared to non-responders (p = 0.024, 0.022, and 0.047, respectively). Additionally, we report a positive correlation between the frequency of T<sub>EM</sub> cells in RSs with age and anti-HBsAb level (p = 0.03 and r<sub>s</sub> = 0.5; p = 0.01 and r<sub>s</sub> = 0.06). Responders display a higher level of CD8<sup>+</sup> T cell-mediated immunity. Therefore, we suggest a possible defect in the formation of immunological CD8<sup>+</sup> memory T cells in NRs and it may reduce antibody production compared to the RSs, although more experiments are needed.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13402"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rashmi Rikhi, Suprit Basu, Kanika Arora, Koon-Wing Chan, Ankur Kumar Jindal, Amit Rawat, Yu-Lung Lau, Deepti Suri
{"title":"Somatic reversion in Wiskott-Aldrich syndrome: Case reports and mechanistic insights.","authors":"Rashmi Rikhi, Suprit Basu, Kanika Arora, Koon-Wing Chan, Ankur Kumar Jindal, Amit Rawat, Yu-Lung Lau, Deepti Suri","doi":"10.1111/sji.13408","DOIUrl":"10.1111/sji.13408","url":null,"abstract":"<p><p>This report describes two brothers from India and a Chinese patient with somatic reversion of an inherited deleterious mutation in the WAS gene. Both the Indian siblings had inherited a single nucleotide deletion causing a frameshift mutation (c.1190del, p.Pro397Argfs*48) (variant 1: marked in blue) from the mother. Another variant (variant 2: marked in red), a 12-nucleotide deletion at position 1188-1199 (c.1188_1199del, p.P401_P404del) was also found, which resulted in restoration of the frame and subsequent rescue of the protein sequence. DNA sequencing from buccal mucosal cells revealed only the inherited variant (variant 1), while no reversion mutation was identified in the mucosal cells. Similarly, the Chinese patient was found to have a novel germline 14-base duplication (ACGAAAATGCTTGG) c.120_132 + 1dup (variant 1). This resulted in abolishment of the original splice junction coupled with the creation of a new junction 14 bases 3' and a frameshift mutation with predicted protein truncation p. Thr45Aspfs*. DNA from the patient's PBMC showed co-existence of wild-type and mutated sequences, but only the mutant was present in the buccal cells. Genomic and mRNA analysis of the isolated CD3+ T lymphocytes, CD3- mononuclear cells, and EBV-transformed B lymphocytes indicated that the reverant variant (germline variant was restored to wild-type sequence) were selectively found in CD3+ T lymphocytes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13408"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phagolysosomal resistance hypothesized to be a danger signal.","authors":"Christopher A Forden","doi":"10.1111/sji.13400","DOIUrl":"10.1111/sji.13400","url":null,"abstract":"<p><p>Antigen presenting cells sometimes require T cell \"help\" to kill and decompose microbes they capture, especially when those microbes resist effector molecules including nitric oxide and reactive oxygen species. Pathogens are more likely to resist those effectors, shared by the innate and adaptive immune systems, than are commensals. Does such resistance alert the immune system to the danger posed by those pathogens? Several lines of evidence suggest this occurs. Mouse studies showed a surprising exacerbation, not alleviation of experimental autoimmune encephalomyelitis, by suppression of nitric oxide production, but only when the suppression was applied to animals undergoing vaccination with myelin. In contrast, animals receiving T cells activated by vaccination without suppression of nitric oxide benefitted from reduced autoimmune cytotoxicity when nitric oxide production was suppressed after adoptive transfer. Vaccinia and adenovirus suppress nitric oxide production and have been successful vaccine platforms, also consistent with the above phagolysosomal resistance hypothesis. The hypothesis solves a long-standing quandary-how can nitric oxide protect against both infection and autoimmunity, especially autoimmune diseases for which it seems a major effector? The importance of physical linkage between epitopes, first proposed in Bretscher's Two-Step, Two-Signal theory dependent on B cells, is extended to include phagolysosomal resistance in general, plus a corollary proposition that the immune system detects resistance to dissociation of high-affinity pathogenic ligands from host binding sites to make neutralizing antibodies.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13400"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayca Ceylan, Mehmet Artac, Mehmet Zahid Kocak, Hasibe Artac
{"title":"Epidermal growth factor receptor and programmed cell death-1 expression levels in peripheral T cell subsets of patients with non-small cell lung cancer.","authors":"Ayca Ceylan, Mehmet Artac, Mehmet Zahid Kocak, Hasibe Artac","doi":"10.1111/sji.13398","DOIUrl":"10.1111/sji.13398","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4<sup>+</sup>T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8<sup>+</sup>follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3<sup>+</sup>T, CD4<sup>+</sup>Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3<sup>+</sup>T, CD4<sup>+</sup>Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3<sup>+</sup>T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3<sup>+</sup>T, CD4<sup>+</sup>Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13398"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}