Scandinavian Journal of Immunology最新文献

{"title":"Blood defense system – Proposal for a new concept of an immune system against blood borne pathogens comprising the liver, spleen and bone marrow","authors":"Makoto Kashimura","doi":"10.1111/sji.13363","DOIUrl":"https://doi.org/10.1111/sji.13363","url":null,"abstract":"Blood‐borne pathogen (BBP) infections can rapidly progress to life‐threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high‐affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long‐lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high‐affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"22 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046051","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":"The presence of autoantibodies as a potential prognostic biomarker for breast cancer","authors":"Libo Ouyang, Keying Jing, Chunkai Zhu, Rong Wang, Peiming Zheng","doi":"10.1111/sji.13365","DOIUrl":"https://doi.org/10.1111/sji.13365","url":null,"abstract":"The presence of autoantibodies is closely associated with the occurrence and development of cancer. Autoantibodies can be used as biomarkers for early breast cancer diagnosis. However, the relationship between autoantibodies and the prognosis of breast cancer patients remains elusive. This retrospective study aimed to investigate the correlation between the presence of autoantibodies and outcomes in breast cancer patients. This study included a total of 155 patients from People's Hospital of Henan University (Zhengzhou, China) who were diagnosed with breast cancer from January 2017 to December 2021. The enrolled patients' clinicopathological features were collected, and 88 patients were ultimately involved in the analysis. Univariate and multivariate Cox regression analyses were performed to search for the risk factors related to the poor prognosis of breast cancer patients. The association between the presence of autoantibodies and patients' survival was analysed using Kaplan–Meier curves. After screening, there were 38 autoantibody‐positive cases and 50 autoantibody‐negative cases. Breast cancer patients with autoantibody‐positive had a 57% lower risk of death compared with autoantibody‐negative patients. Multivariate Cox regression analysis indicated that the presence of autoantibody could be a potential prognostic predictor for breast cancer, independent of age, histological grade, pathological classification, clinical stage, and the expression levels of hormonal receptors. In addition, autoantibody‐positive breast cancer patients had longer progression‐free survival and overall survival compared with autoantibody‐negative cases. Positive autoantibody was found as an independent biomarker of better prognosis in breast cancer patients, providing a new strategy for the prognostic assessment of breast cancer patients.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"21 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002270","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":"Interaction of T-cell-specific adapter protein with Src- and Tec-family kinases","authors":"Zsuzsa Huszenicza, Brian C. Gilmour, Lise Koll, Hanna Kjelstrup, Hanna Chan, Vibeke Sundvold, Stine Granum, Anne Spurkland","doi":"10.1111/sji.13358","DOIUrl":"https://doi.org/10.1111/sji.13358","url":null,"abstract":"Adapter proteins are flexible and dynamic modulators of cellular signalling that are important for immune cell function. One of these, the T-cell-specific adapter protein (TSAd), interacts with the non-receptor tyrosine kinases Src and Lck of the Src family kinases (SFKs) and Itk of the Tec family kinases (TFKs). Three tyrosine residues in the TSAd C-terminus are phosphorylated by Lck and serve as docking sites for the Src homology 2 (SH2) domains of Src and Lck. The TSAd proline-rich region (PRR) binds to the Src homology 3 (SH3) domains found in Lck, Src and Itk. Despite known interactors, the role TSAd plays in cellular signalling remains largely unknown. TSAd's ability to bind both SFKs and TFKs may point to its function as a general scaffold for both kinase families. Using GST-pulldown as well as peptide array experiments, we found that both the SH2 and SH3 domains of the SFKs Fyn and Hck, as well as the TFKs Tec and Txk, interact with TSAd. This contrasts with Itk, which interacts with TSAd only through its SH3 domain. Although our analysis showed that TSAd is both co-expressed and may interact with Fyn, we were unable to co-precipitate Fyn with TSAd from Jurkat cells, as detected by Western blotting and affinity purification mass spectrometry. This may suggest that TSAd-Fyn interaction in intact cells may be limited by other factors, such as the subcellular localization of the two molecules or the co-expression of competing binding partners.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"9 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584851","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":"Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection","authors":"Charles W. Armitage, Emily R. Bryan, Logan Trim, Ella Palframan, Lucas Wager, Kenneth W. Beagley, Alison J. Carey","doi":"10.1111/sji.13359","DOIUrl":"https://doi.org/10.1111/sji.13359","url":null,"abstract":"<i>Chlamydia trachomatis</i> infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early <i>Chlamydia muridarum</i> infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A^−/− mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A^−/− immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)^−/− female mice and observed a significant reduction in immunopathology in IL17RA^−/− mice. WT bone marrow transplants to IL17RA^−/− recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early <i>C. muridarum</i> infection of the female reproductive tract.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"32 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139517985","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":"The role of hormones in ILC2-driven allergic airway inflammation","authors":"Zhongling Dai, Zhande Gong, Cui Wang, WeiXiang Long, Duo Liu, Haijun Zhang, Aihua Lei","doi":"10.1111/sji.13357","DOIUrl":"https://doi.org/10.1111/sji.13357","url":null,"abstract":"Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"54 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139517811","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":"Unlocking PD-1 antibody resistance: The MUC1 DNA vaccine augments CD8+ T cell infiltration and attenuates tumour suppression","authors":"Xiaoqin Wang, Yinsha Miao, Jinghui Shen, Dandan Li, Xinyue Deng, Chengcheng Yang, Yanhong Ji, ZhiJun Dai, Yunfeng Ma","doi":"10.1111/sji.13356","DOIUrl":"https://doi.org/10.1111/sji.13356","url":null,"abstract":"In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8⁺ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8⁺/CD4⁺ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"3 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139518034","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":"Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells","authors":"Ke Zhu, Chen Liu, Xiaofang Guo, Xuting Zhang, Jiaxin Xie, Songmiao Xie, Qing Qi, Bin Yang","doi":"10.1111/sji.13354","DOIUrl":"https://doi.org/10.1111/sji.13354","url":null,"abstract":"Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPARγ, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"14 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498207","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":"Predictive model for CAR-T cell therapy success in patients with relapsed/refractory B-cell acute lymphoblastic leukaemia","authors":"Lianfang Pu, Huiping Wang, Fan Wu, Furun An, Hao Xiao, Yangyang Wang, Xue Liang, Zhimin Zhai","doi":"10.1111/sji.13352","DOIUrl":"https://doi.org/10.1111/sji.13352","url":null,"abstract":"Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B-cell lymphoblastic leukaemia (R/R B-ALL). However, a subset of patients does not benefit from CAR-T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR-T therapy. Fifty-five R/R B-ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B-MRD) as indicators for predicting the success of CAR-T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3⁺ T count, CD4⁺ T/CD8⁺ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR-T therapy with AUC of 0.938. Notably, a model based on CD4⁺ T/CD8⁺ T ratio, B, Treg and EMD were used in predicting the success of CAR-T therapy with AUC 0.966 [0.908–1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR-T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR-T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR-T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR-T cell therapy.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498243","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":"Concerns about the histological assessment in a mouse model of human celiac disease","authors":"Tobias L. Freitag, Leif C. Andersson, Anja Kipar","doi":"10.1111/sji.13351","DOIUrl":"https://doi.org/10.1111/sji.13351","url":null,"abstract":"&lt;p&gt;Celiac disease (CD) is a common immune-mediated, gluten-sensitive enteropathy that develops in human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 allele carriers due to the dysregulation of gluten-specific T helper cells. Although ingested gluten from cereals was identified as the disease driver in the 1950s, the ultimate cause (or disease trigger) remains unknown. CD is further characterized by the production by intestinal B cells of autoantibodies against tissue transglutaminase 2, an enzyme that can modify gluten peptides by deamidation, thus rendering gluten more recognizable for celiac patient T cells. The celiac intestinal lesion is hallmarked by crypt hyperplasia and villus atrophy, but also by intraepithelial T cells and lamina propria plasma cell infiltration.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;So far, an accurate CD model in rodents that would unite the features listed above does not exist.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; HLA-DQ2 or HLA-DQ8 transgenic, mouse class II knockout models provide appropriate restriction of T helper cells, valuable for the experimental study of cellular and humoral immune responses directed at gluten. But HLA-transgenic mice do not develop disease on gluten-containing diet, or following various additional challenges, while any histological changes in the intestine remain mild and rudimentary.&lt;span&gt;&lt;sup&gt;4-7&lt;/sup&gt;&lt;/span&gt; In contrast, Rag1&lt;sup&gt;−/−&lt;/sup&gt; mice adoptively transferred with gliadin memory T cells have been described as a CD model with an intestinal phenotype that includes villus atrophy, crypt hyperplasia and mucosal mononuclear cell infiltration.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; However, the gluten-sensitive enteropathy in this model depends on the quantitative depletion of regulatory T cells. Consequently, negative control mice on gluten-free diet also show mild-to-moderate (autoimmune) enteropathy.&lt;/p&gt;\u0000&lt;p&gt;In-depth histological analyses are vital for the development of animal models of human diseases. Since CD primarily affects the proximal small intestine, and is characterized by well-documented histological changes,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; thorough histological investigation of at least the entire small intestine, that is, duodenum, jejunum and ileum, is key for the validation of any animal model of human CD.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Non-validated surrogate biomarkers such as immune mediators or anti-gliadin antibodies cannot replace histological parameters. The assessment of architectural changes in the small intestine forms an important part of the histological analysis in CD and its animal models. However, it is well known that villus/crypt (V/C) ratios are notoriously unreliable as sole parameters of intestinal damage for various reasons; they are affected by diets, the age of the animal, and location in the intestinal compartment, as well as technical issues, for example, sampling consistency,&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; tissue orientation&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; or compression by luminal content. Intraepithel","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"2615 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498204","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":"Antibody responses to immunoevasion proteins BBK32 and OspE constitute part of the serological footprint in neuroborreliosis but are insufficient to prevent the disease","authors":"Vinaya Dulipati, Juha Kotimaa, Mikel Rezola, Mikko Kontiainen, Hanna Jarva, Dag Nyman, Seppo Meri","doi":"10.1111/sji.13353","DOIUrl":"https://doi.org/10.1111/sji.13353","url":null,"abstract":"Lyme borreliosis, caused by <i>Borrelia burgdorferi</i> sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. <i>Borrelia</i> outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B-cell recruitment during neuroinflammation, in patients' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well-characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K-means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti-BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti-ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421742","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}