Immunogenetics最新文献

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The antigen recognition portion of African buffalo class I MHC is highly polymorphic, consistent with a complex pathogen challenge environment, and the 3' region suggests distinct haplotype configurations. 非洲水牛I类MHC抗原识别部分具有高度多态性,与复杂的病原体挑战环境相一致,并且3'区域显示出不同的单倍型配置。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-022-01287-0
Isaiah Obara, Ard Nijhof, Patrick Atimnedi, Domnic Mijele, Anne Nanteza, Khawla Elati, Richard Bishop
{"title":"The antigen recognition portion of African buffalo class I MHC is highly polymorphic, consistent with a complex pathogen challenge environment, and the 3' region suggests distinct haplotype configurations.","authors":"Isaiah Obara,&nbsp;Ard Nijhof,&nbsp;Patrick Atimnedi,&nbsp;Domnic Mijele,&nbsp;Anne Nanteza,&nbsp;Khawla Elati,&nbsp;Richard Bishop","doi":"10.1007/s00251-022-01287-0","DOIUrl":"https://doi.org/10.1007/s00251-022-01287-0","url":null,"abstract":"<p><p>African buffalo (Syncerus caffer) have been distinct from the Auroch lineage leading to domestic cattle for 5 million years, and are reservoirs of multiple pathogens, that affect introduced domestic cattle. To date, there has been no analysis of the class I MHC locus in African buffalo. We present the first data on African buffalo class I MHC, which demonstrates that gene and predicted protein coding sequences are approximately 86-87% similar to that of African domestic cattle in the peptide binding region. The study also shows concordance in the distribution of codons with elevated posterior probabilities of positive selection in the buffalo class I MHC and known antigen binding sites in cattle. Overall, the diversity in buffalo class I sequences appears greater than that in cattle, perhaps related to a more complex pathogen challenge environment in Africa. However, application of NetMHCpan suggested broad clustering of peptide binding specificities between buffalo and cattle. Furthermore, in the case of at least 20 alleles, critical peptide-binding residues appear to be conserved with those of cattle, including at secondary anchor residues. Alleles with six different length transmembrane regions were detected. This preliminary analysis suggests that like cattle, but unlike most other mammals, African buffalo appears to exhibit configuration (haplotype) variation in which the loci are expressed in distinct combinations.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"115-132"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9196397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Expression analysis of Carassius auratus-leukocyte-immune-type receptors (CaLITRs) during goldfish kidney macrophage development and in activated kidney leukocyte cultures. 金鱼肾巨噬细胞发育和活化肾白细胞培养中鲫鱼白细胞免疫型受体(CaLITRs)的表达分析。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-023-01298-5
Jiahui Wang, Amro M Soliman, Jeff Norlin, Daniel R Barreda, James L Stafford
{"title":"Expression analysis of Carassius auratus-leukocyte-immune-type receptors (CaLITRs) during goldfish kidney macrophage development and in activated kidney leukocyte cultures.","authors":"Jiahui Wang,&nbsp;Amro M Soliman,&nbsp;Jeff Norlin,&nbsp;Daniel R Barreda,&nbsp;James L Stafford","doi":"10.1007/s00251-023-01298-5","DOIUrl":"https://doi.org/10.1007/s00251-023-01298-5","url":null,"abstract":"<p><p>Carassius auratus leukocyte immune-type receptors (CaLITRs) were recently discovered immunoregulatory receptors in goldfish that have diverse immunoglobulin-like (Ig-like) ectodomains and intracellular signaling motifs. Genomic analysis shows that CaLITR-types are also located as distinct gene clusters across multiple goldfish chromosomes. For example, CaLITR1 (unplaced) is a functionally ambiguous receptor having two Ig-like domains, a transmembrane domain (TM), and a short cytoplasmic tail (CYT) devoid of any recognizable signaling motifs. CaLITR2 (Chr47) is a putative inhibitory receptor containing four Ig-like domains, a TM, and a long CYT with an immunoreceptor tyrosine-based inhibition motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM). A putative activating receptor-type, CaLITR3 (Chr3), has four Ig-like domains, a TM, and a short CYT containing a positively charged histidine residue and CaLITR4 (ChrLG28B) is a receptor with putative multifunctional signaling potential as well as five Ig-like domains, a TM, and a long tyrosine-motif containing CYT region. The variable genomic locations of the CaLITRs suggest that they are likely under the influence of different cis- and/or trans-regulatory elements. To better understand the transcriptional activities of select CaLITRs from variable genomic regions, we used an RT-qPCR-based approach to examine the expression of CaLITR1, CaLITR2, CaLITR3, and CaLITR4 during goldfish primary kidney macrophage (PKM) development and in mixed leukocyte reaction cultures (MLRs) of the goldfish. Our results showed that the select CaLITRs are differentially expressed during PKM development and in goldfish MLRs exposed to T-cell mitogens/immunosuppressive drugs, supporting that the transcription of these CaLITRs is likely regulated by distinct cis- and/or trans-regulatory elements.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"171-189"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9250691","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}
引用次数: 1
Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain. 全外显子组测序鉴定出白细胞介素2受体α链剪接供体位点的新变异。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-022-01278-1
Nadia Waheed, Maryam Naseer, Nighat Haider, Sufyan Suleman, Asmat Ullah
{"title":"Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain.","authors":"Nadia Waheed,&nbsp;Maryam Naseer,&nbsp;Nighat Haider,&nbsp;Sufyan Suleman,&nbsp;Asmat Ullah","doi":"10.1007/s00251-022-01278-1","DOIUrl":"https://doi.org/10.1007/s00251-022-01278-1","url":null,"abstract":"<p><p>Interleukin 2 receptor alpha chain (IL-2Rα or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in the IL-2Rα gene encoding IL-2Rα also known as CD25 protein. IL-2Rα combines with γ and β chains of interleukin 2 receptor to form a functional interleukin 2 receptor (IL-2R). In the present study, we identified a Pakistani family presenting a unique presentation of IL-2Rα deficiency. Clinical whole exome sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G > A) in the IL-2Rα gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. The IL-2Rα gene mutation usually presents with autoimmunity and immunodeficiency but in our patient, it presents with congenital diarrhea, metabolic crisis, and strong family history of death in infancy due to the similar complications. Her congenital diarrhea is attributed to autoimmunity in the form of autoimmune enteropathy and eczema. The laboratory findings revealed severe metabolic acidosis hypokalemia and elevated lactate and ammonia levels. This is a new presentation of IL-2Rα gene mutation. The present study highlights the importance of clinical whole exome sequencing in the correct diagnosis of congenital disorders. The study will also help clinical geneticists for genetic counseling and prevention of the disease in the affected family.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"71-79"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548656","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}
引用次数: 0
Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation. 肿瘤坏死因子-α通过激活STAT3诱导结直肠癌细胞增殖并减少凋亡。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-023-01302-y
Wei Wei, Juanhong Wang, Pu Huang, Siqi Gou, Daihua Yu, Lei Zong
{"title":"Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation.","authors":"Wei Wei,&nbsp;Juanhong Wang,&nbsp;Pu Huang,&nbsp;Siqi Gou,&nbsp;Daihua Yu,&nbsp;Lei Zong","doi":"10.1007/s00251-023-01302-y","DOIUrl":"https://doi.org/10.1007/s00251-023-01302-y","url":null,"abstract":"<p><p>Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory factor that plays an important role in establishing a complicated connection between inflammation and cancer. TNF-α promotes tumor proliferation, migration, invasion, and angiogenesis according to numerous studies. Studies have shown the significant role of STAT3, a downstream transcription factor of another important inflammatory cytokine, IL-6 in the development and progression of different tumors especially colorectal cancer. In the present study, we investigated whether TNF-α has a role in proliferation and apoptosis of colorectal cancer cells through STAT3 activation. HCT116 cell line as human colorectal cancer cells was used in this study. Major assays were MTT assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that TNF-α significantly increased the phosphorylation of STAT3 and expression of all the STAT3 target genes related to cell proliferation, survival, and metastasis compared with control. Moreover, our data showed that the STAT3 phosphorylation and expression of its target genes significantly were reduced in the presence of TNF-α + STA-21 compared with TNF-α-treated group demonstrating that the increase in genes expression partially was due to the TNF-α-induced STAT3 activation. On the other hand, STAT3 phosphorylation and mRNA levels of its target genes were partially decreased in the presence of TNF-α + IL-6R supporting the indirect pathway of STAT3 activation by TNF-α through inducing IL-6 production in cancer cells. Given the growing evidence for STAT3 as a key mediator of inflammation-induced colon cancer, our findings support further investigation of STAT3 inhibitors as potential cancer therapies.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"161-169"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9197211","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}
引用次数: 1
Assessment of regulatory T cells (Tregs) and Foxp3 methylation level in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy. 评估接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的调节性 T 细胞(Tregs)和 Foxp3 甲基化水平。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 Epub Date: 2022-12-26 DOI: 10.1007/s00251-022-01291-4
Shahla'a Fadhil Sabir, Bassam Francis Matti, Wifaq Mahmood Ali Alwatar
{"title":"Assessment of regulatory T cells (Tregs) and Foxp3 methylation level in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy.","authors":"Shahla'a Fadhil Sabir, Bassam Francis Matti, Wifaq Mahmood Ali Alwatar","doi":"10.1007/s00251-022-01291-4","DOIUrl":"10.1007/s00251-022-01291-4","url":null,"abstract":"<p><p>The key cell population permits cancer cells to avoid immune-surveillance is regulatory T cells (Tregs). This study evaluates the level of Tregs in chronic myeloid leukemia (CML) patients and the effect of Tyrosine kinase inhibitor (TKI) on Treg levels, as a pathway to understand the immune response and behavior among advance stage and optimal response CML patients using imatinib therapy. Blood samples were collected from 30 CML patients (optimal response to TKI), 30 CML patients (failure response to TKI), and 30 age- and gender-matched controls. Analysis involved measuring percentages of Tregs (CD4 + CD25 + FOXP3 +) by flow cytometer and demethylation levels of FOXP3 Treg-specific demethylated region (TSDR) by PCR. The data revealed that Tregs and the FOXP3-TSDR demethylation percentages significantly increased in failure response group in comparison to the optimal response and control groups, while no significant difference between optimal response and control groups. Tregs and FOXP3 TSDR demethylation percentages showed high sensitivity and specificity, suggesting powerful discriminatory biomarkers between failure and optimal groups. An assessment of the Tregs and demethylation percentage among different BCR-ABL levels of CML patients on TKI revealed no significant differences in parameter percentage in the optimal response to TKI patients with different molecular responses (log 3 reduction or other deeper log 4.5 and 5 reduction levels). Our findings demonstrate an effective role of functional Tregs among different CML stages. Also, the study suggests that the major molecular response to therapy at level 0.1% of BCR-ABL transcript could be enough to induce immune system restoration in patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"145-153"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9196806","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}
引用次数: 0
X-linked hyper-immunoglobulin M syndrome harboring a novel CD40-ligand gene mutation: a case report. 携带一种新的cd40配体基因突变的x连锁超免疫球蛋白M综合征:一例报告。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-022-01289-y
Rahul Ramachandran, Yamini Krishnan, Parminder Singh, Ashok Kumar, Abhishek Mohanty
{"title":"X-linked hyper-immunoglobulin M syndrome harboring a novel CD40-ligand gene mutation: a case report.","authors":"Rahul Ramachandran,&nbsp;Yamini Krishnan,&nbsp;Parminder Singh,&nbsp;Ashok Kumar,&nbsp;Abhishek Mohanty","doi":"10.1007/s00251-022-01289-y","DOIUrl":"https://doi.org/10.1007/s00251-022-01289-y","url":null,"abstract":"<p><p>The X-linked hyper-IgM syndrome (X-HIGM1) is a rare primary immunodeficiency disorder (PID) caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). X-HIGM1 is characterized by normal or elevated serum levels of IgM in association with decreased levels of IgG, IgA, and IgE. The CD40LG protein expressed on activated T cells interacts with its receptor protein, CD40, on B lymphocytes and dendritic cells. Mutations in the CD40LG gene lead to the production of an abnormal CD40L protein that fails to attach to its receptor, CD40 on B cells resulting in failure to produce IgG, IgA, and IgE antibodies. In the present study, we investigated the molecular defects underlying such a PID in a patient presenting with clinical history of pneumonia and acute respiratory distress syndrome (ARDS) at 7 months of age and diagnosed as transient hypogammaglobulinemia with decreased levels of IgG and increased levels of IgM. We have identified a novel and yet to be reported frame shift deletion of a single base pair (c.229delA) in exon 2 (p.Arg77AspfsTer6) of the CD40L gene ensuing the premature truncation of the protein by 6 amino acids by targeted gene sequencing. This frame shift mutation identified as a CD40L variant was found to be pathogenic which was also validated by Sanger sequencing. The in-silico analysis of c.229 del A mutation also predicted the change to be pathological affecting the structure and function of the CD40L (CD40L, CD154) protein and its protein-protein interaction properties.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"191-194"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201473","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}
引用次数: 0
Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19. IFIH1/MDA5基因变异对COVID-19危重症风险的年龄依赖性影响
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-022-01281-6
María G Muñiz-Banciella, Guillermo M Albaiceta, Laura Amado-Rodríguez, Estefanía Salgado Del Riego, Inés López Alonso, Cecilia López-Martínez, Paula Martín-Vicente, Marta García-Clemente, Tamara Hermida-Valverde, Ana I Enríquez-Rodriguez, Cristina Hernández-González, Elías Cuesta-Llavona, Victoria Alvarez, Juan Gómez, Eliecer Coto
{"title":"Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.","authors":"María G Muñiz-Banciella,&nbsp;Guillermo M Albaiceta,&nbsp;Laura Amado-Rodríguez,&nbsp;Estefanía Salgado Del Riego,&nbsp;Inés López Alonso,&nbsp;Cecilia López-Martínez,&nbsp;Paula Martín-Vicente,&nbsp;Marta García-Clemente,&nbsp;Tamara Hermida-Valverde,&nbsp;Ana I Enríquez-Rodriguez,&nbsp;Cristina Hernández-González,&nbsp;Elías Cuesta-Llavona,&nbsp;Victoria Alvarez,&nbsp;Juan Gómez,&nbsp;Eliecer Coto","doi":"10.1007/s00251-022-01281-6","DOIUrl":"https://doi.org/10.1007/s00251-022-01281-6","url":null,"abstract":"<p><p>MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18-2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"91-98"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9702716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9249121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Correction to: Llama peripheral B-cell populations producing conventional and heavy chain-only IgG subtypes are phenotypically indistinguishable but immunogenetically distinct. 修正:产生常规和仅重链IgG亚型的羊驼外周b细胞群在表型上无法区分,但在免疫遗传学上是不同的。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-023-01299-4
Kevin A Henry, Henk van Faassen, Doreen Harcus, Anne Marcil, Jennifer J Hill, Serge Muyldermans, C Roger MacKenzie
{"title":"Correction to: Llama peripheral B-cell populations producing conventional and heavy chain-only IgG subtypes are phenotypically indistinguishable but immunogenetically distinct.","authors":"Kevin A Henry,&nbsp;Henk van Faassen,&nbsp;Doreen Harcus,&nbsp;Anne Marcil,&nbsp;Jennifer J Hill,&nbsp;Serge Muyldermans,&nbsp;C Roger MacKenzie","doi":"10.1007/s00251-023-01299-4","DOIUrl":"https://doi.org/10.1007/s00251-023-01299-4","url":null,"abstract":"","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"195"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541412","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}
引用次数: 0
Unfavorable immunotherapy plus tyrosine kinase inhibition outcome of metastatic renal cell carcinoma after radical nephrectomy with increased ADAM9 expression. 不良免疫治疗加酪氨酸激酶抑制转移性肾癌根治性肾切除术后ADAM9表达升高的结果。
IF 3.2 4区 医学
Immunogenetics Pub Date : 2023-04-01 DOI: 10.1007/s00251-022-01292-3
Xianglai Xu, Ying Wang, Zhaoyi Chen, Yanjun Zhu, Jiajun Wang, Jianming Guo
{"title":"Unfavorable immunotherapy plus tyrosine kinase inhibition outcome of metastatic renal cell carcinoma after radical nephrectomy with increased ADAM9 expression.","authors":"Xianglai Xu,&nbsp;Ying Wang,&nbsp;Zhaoyi Chen,&nbsp;Yanjun Zhu,&nbsp;Jiajun Wang,&nbsp;Jianming Guo","doi":"10.1007/s00251-022-01292-3","DOIUrl":"https://doi.org/10.1007/s00251-022-01292-3","url":null,"abstract":"<p><p>Immunotherapy plus tyrosine kinase inhibitor (IO-TKI) has become the standard first-line therapy for advanced renal cell carcinoma (RCC). However, the modest response rate of IO-TKI therapy and the absence of biomarkers limited the selection of treatment strategies for RCC patients. There were three cohorts enrolled: two from our facility (ZS-MRCC and ZS-HRRCC) and one from a clinical study (JAVELIN-101). By RNA sequencing, the expression of ADAM9 in each sample was measured. By flow cytometry and immunohistochemistry, immune infiltration and T cell function were examined. Primary outcomes were established as treatment response and progression-free survival (PFS). Patients with low-ADAM9 expression had a higher objective response rate (56.5% vs 13.6%, P = 0.01) and longer PFS in both cohorts. In the ZS-HRRCC cohort, the expression of ADAM9 was associated with increased tumor-infiltrating T cells, which was proved by immunohistochemistry (P < 0.05) and flow cytometry (Spearman's ρ = 0.42, P < 0.001). In the high-ADAM9 group, CD8<sup>+</sup> and CD4<sup>+</sup> T cells revealed an exhausted phenotype with decreased GZMB (Spearman's ρ =  - 0.31, P = 0.05, and Spearman's ρ =  - 0.49, P < 0.001, respectively), and fewer Macrophages were identified. A predictive RFscore was further constructed by random forest approach, involving ADAM9 and immunologic genes. Only in the subgroup with the lower RFscore did IO-TKI outperform TKI monotherapy. High-ADAM9 expression was associated with immunosuppression and IO-TKI resistance. Expression of ADAM9 was also associated with the exhaustion and dysfunction of T cells. ADAM9-based RFscore has the potential to be used as a biomarker to distinguish the optimal patient treatment methods between IO-TKI and TKI monotherapy.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 2","pages":"133-143"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201482","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}
引用次数: 0
Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses. 人类免疫球蛋白 G 亚类异型多态性的功能性后果。
IF 2.9 4区 医学
Immunogenetics Pub Date : 2023-02-01 Epub Date: 2022-07-29 DOI: 10.1007/s00251-022-01272-7
Andrew R Crowley, Simone I Richardson, Marina Tuyishime, Madeleine Jennewein, Meredith J Bailey, Jiwon Lee, Galit Alter, Guido Ferrari, Lynn Morris, Margaret E Ackerman
{"title":"Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses.","authors":"Andrew R Crowley, Simone I Richardson, Marina Tuyishime, Madeleine Jennewein, Meredith J Bailey, Jiwon Lee, Galit Alter, Guido Ferrari, Lynn Morris, Margaret E Ackerman","doi":"10.1007/s00251-022-01272-7","DOIUrl":"10.1007/s00251-022-01272-7","url":null,"abstract":"<p><p>Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors' affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed, label-free biophysical methods and cell-based functional assays to determine what effect, if any, human IgG polymorphisms have on antibody function. While we observed several differences in FcγR affinity among allotypes, there was little evidence of dramatically altered FcγR-based effector function or antigen recognition activity associated with this aspect of genetic variability.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"75 1","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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