{"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}
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}
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}
Shuting Lin, Dong Lai, Yan Tian, Fei Lai, Min Long, Changfu Ji, Gengxin Hao
{"title":"MicroRNA hsa-let-7e-5p in hUC-MSC-EVs alleviates oral mucositis by targeting TAB2.","authors":"Shuting Lin, Dong Lai, Yan Tian, Fei Lai, Min Long, Changfu Ji, Gengxin Hao","doi":"10.1111/sji.13399","DOIUrl":"10.1111/sji.13399","url":null,"abstract":"<p><p>Oral mucositis (OM) is a severe side effect of anti-cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC-MSC-EVs) and investigated their role in lipopolysaccharide (LPS)-induced human oral keratinocytes (HOKs). We observed that treatment with hUC-MSC-EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA-seq using miRNAs extracted from hUC-MSC-EVs, we identified hsa-let-7e-5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa-let-7e-5p may inhibit the NF-κB signalling pathway by targeting TAB2. Overexpression of the hsa-let-7e-5p inhibitor significantly attenuated the anti-inflammatory effect of hUC-MSC-EVs in LPS-induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC-MSC-EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa-let-7e-5p in hUC-MSC-EVs could protect the oral mucosa from OM by repressing TAB2 expression.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13399"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789014","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":"Early graft-infiltrating lymphocytes are not associated with graft rejection in a mouse model of skin transplantation.","authors":"Ryo Kanazawa, Ryoichi Goto, Takuya Harada, Takuji Ota, Nozomi Kobayashi, Kazuaki Shibuya, Yoshikazu Ganchiku, Masaaki Watanabe, Masaaki Zaitsu, Norio Kawamura, Tsuyoshi Shimamura, Akinobu Taketomi","doi":"10.1111/sji.13397","DOIUrl":"10.1111/sji.13397","url":null,"abstract":"<p><p>Graft-infiltrating lymphocytes (GILs) play an important role in promoting rejection after organ transplantation. We recently reported that GILs that accumulated up to 3 days post-transplantation did not promote rejection, whereas GILs present 3-5 days post-transplantation promoted rejection in a mouse heart transplantation model. However, the immunological behaviour of GILs in murine skin transplantation remains unclear. GILs were isolated on days 3, 5 or 7 post-transplantation from C57BL/6 (B6) allogeneic skin grafts transplanted onto BALB/c mice. BALB/c Rag2<sup>-/-</sup> γc<sup>-/-</sup> mice (BRGs) underwent B6 skin graft transplantation 10 weeks after adoptive transfer of day 3, 5, or 7 GILs. BRGs reconstituted with day 5 or 7 GILs completely rejected B6 grafts. However, when B6 grafts harvested from recipient BALB/c mice on day 5 or 7 were re-transplanted into BRGs, half of the re-transplanted day 5 grafts established long-term survival, although all re-transplanted day 7 grafts were rejected. BRGs reconstituted with day 3 GILs did not reject B6 grafts. Consistently, re-transplantation using day 3 skin grafts resulted in no rejection. Administration of anti-CD25 antibodies did not prevent the phenomenon observed for the day 3 skin grafts. Furthermore, BRGs reconstituted with splenocytes from naïve BALB/c mice immediately rejected the naïve B6 skin grafts and the re-transplanted day 3 B6 grafts, suggesting that day 3 GILs were unable to induce allograft rejection during the rejection process. In conclusion, the immunological role of GILs depends on the time since transplantation. Day 3 GILs had neither protective nor alloreactive effects in the skin transplant model.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13397"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856408","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}
Ole Bernt Lenning, Grete Jonsson, Tore Grimstad, Emiel A. M. Janssen, Geir Sverre Braut, Frode Berven, Roald Omdal
{"title":"No signs of mast cell involvement in long‐COVID: A case–control study","authors":"Ole Bernt Lenning, Grete Jonsson, Tore Grimstad, Emiel A. M. Janssen, Geir Sverre Braut, Frode Berven, Roald Omdal","doi":"10.1111/sji.13407","DOIUrl":"https://doi.org/10.1111/sji.13407","url":null,"abstract":"Long‐COVID caused by SARS‐CoV‐2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells—evolutionary old “multipurpose” innate immune cells—was reported recently in studies of acute infection and post‐acute‐COVID‐19 syndrome. Mast cell activity has been suggested in long‐COVID. In this case–control study, we compared data from 24 individuals with long‐COVID (according to the NICE criteria) and 24 age‐ and sex‐matched healthy individuals with a history of SARS‐CoV‐2 infection without developing sequelae. Serum levels of the proteases beta‐tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance. TPSB2 and CPA3 levels were median (range) 26.9 (2.0–1000) and 5.8 (1.5–14.0) ng/mL, respectively, in the long‐COVID group. The corresponding values in the control group were 10.9 (2.0–1000) (<jats:italic>p</jats:italic> = 0.93) and 5.3 (3.5–12.9) ng/mL (<jats:italic>p</jats:italic> = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF‐36, 3.1–3.10 were revealed. We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long‐COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long‐term pathogenesis of long‐COVID, at least in the majority of patients.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"19 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256646","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":"Relevance of antigen‐induced IL‐6 and mitogen‐induced or spontaneous IFN‐γ secretions in whole blood cultures for detection of Mycobacterium tuberculosis infection and disease","authors":"Sudhir Sinha, Komal Singh, Fareha Umam, Prerna Kapoor, Amita Aggarwal","doi":"10.1111/sji.13406","DOIUrl":"https://doi.org/10.1111/sji.13406","url":null,"abstract":"For an effective control of tuberculosis (TB), there is a persistent need for biomarkers that can report true estimates of TB infection (TBI) and predict its progression towards active TB disease. We investigated whether the cell‐mediated immune responses to <jats:italic>Mycobacterium tuberculosis</jats:italic> (Mtb) antigens could provide such biomarkers. The study subjects (<jats:italic>n</jats:italic> = 174) comprised a cohort of smear‐positive, drug‐sensitive, HIV‐negative pulmonary TB patients (<jats:italic>n</jats:italic> = 54) and their household contacts (HC, <jats:italic>n</jats:italic> = 120). Whole blood cultures, in the presence or absence of Mtb antigens‐ membrane (MtM), purified protein derivative (PPD) and alpha‐crystallin (Acr), or the mitogen PHA were subjected to determinations, by flow cytometry, for T cell proliferative and, by ELISA, for IFN‐γ, TNF‐α, and IL‐6 cytokine responses. Additionally, serum levels of the three cytokines were also estimated. The strongest cell‐proliferative and cytokine responses were induced by MtM and IL‐6 was the most abundantly produced cytokine. While none of the responses induced by Mtb antigens or the serum cytokines levels could discriminate between TB and HC, the ex vivo cytokine responses induced by PHA or ‘spontaneously’ could apparently do so. The concentrations of IFN‐γ induced by PHA in TB blood cultures were significantly lower than in HC cultures (AUC = 0.72). Conversely, the spontaneous IFN‐γ or TNF‐α secretions in TB cultures were significantly higher than in HC cultures (AUC = 0.66). Our results suggest that IL‐6 responses to MtM could be a sensitive indicator of TBI, and low levels of PHA‐induced or high levels of spontaneous IFN‐γ secretions in HC blood cultures may indicate a progressive infection.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256643","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}