Ask about this productRelated genes to: SH2D1A Blocking Peptide
- Gene:
- SH2D1A NIH gene
- Name:
- SH2 domain containing 1A
- Previous symbol:
- IMD5, LYP
- Synonyms:
- XLP, MTCP1, DSHP, XLPD, EBVS, SAP
- Chromosome:
- Xq25
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-30
- Date modifiied:
- 2019-04-23
Related products to: SH2D1A Blocking Peptide
Related articles to: SH2D1A Blocking Peptide
- Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in malignant melanoma, yet accessible, tissue-based predictive biomarkers of response remain limited. PD-L1 expression, which remains widely used, offers some prognostic value but performs poorly at low expression levels. We performed liquid chromatography-mass spectrometry proteomic profiling on 185 melanoma samples, including 52 pretreatment samples from ICI responders and nonresponders. Differential expression and pathway analyses identified a 73-protein immune activation signature correlating with ICI response. Within this immune context, SH2D1A (SAP), a regulator of T- and natural killer-cell cytotoxicity, emerged as a top candidate biomarker. Internal immunohistochemical validation confirmed its strong predictive accuracy (area under the receiver operating characteristic curve: 0.93; sensitivity: 88%; specificity: 91%) in distinguishing responders from nonresponders, outperforming PD-L1, CD3, and CD8. Notably, SH2D1A retained its predictive power in PD-L1-low tumors (combined positive score < 10), suggesting clinical use in which the current markers fall short. Independent validation in an external tissue microarray cohort revealed attenuated predictive performance, likely reflecting the impact of intratumoral heterogeneity, as further suggested by whole-slide validation. Nevertheless, SH2D1A remained significantly enriched in tumors that responded to ICIs and was associated with improved survival outcomes, outperforming CD3, CD8, and PD-L1. In conclusion, these results suggest that SH2D1A provides information beyond established immune infiltration- and exhaustion-related markers, supporting further investigation of its potential role in biomarker-guided prediction of ICI response in melanoma. - Source: PubMed
Publication date: 2026/03/24
Fusco FedericoWeigel JohannesSchliemann MariusSchneider AnnikaZhou YuxiangPersa Oana-DianaPosch ChristianKrackhardt AngelaFörg SarahSchott ChristinaSteiger KatjaMogler CarolinGaumann AndreasKuster BernhardKuhn Peer-Hendrik - A small percentage of people living with HIV (PLHIV) spontaneously regulate viral replication without suppressive antiretroviral treatment (ART) and are categorized into 'elite controllers' (EC, HIV-RNA < 50 c/mL) and 'viremic controllers' (VC, HIV-RNA between 50-10,000 c/ml). Some EC and VC may lose controller status in time. Here we provide extensive plasma proteomics to identify biomarkers and pathways related to spontaneous viral control and its long-term preservation among 36 EC and 147 VC (discovery) and 14 EC and 5 VC (validation). VC exhibited higher concentrations of CRTAM, LY9, and CD6 and lower concentrations of VAT1 compared to EC in both the discovery and validation cohort. Longitudinal analysis of pre- and post-ART samples (median follow-up: 5.3 years) revealed downregulation of various immune-related proteins in both EC and VC. Over a 17-year follow-up period, loss of viral control occurred in 31% of VC and 3% of EC. T-cell associated proteins (CRTAM, LY9, CD6), along with ICAM3, SH2D1A, C1QL2, and CNGB3, predicted loss of viral control years before its occurrence. Markers of chronic immune activation (sPD-L1, sCD25, IL-10, TGF-β, IFN-γ, and TNF-α) and systemic inflammation (TNF, IL-1β, IL-6, and sCD14) were not predictive. Our findings underscore the dynamic interplay between T cell function and viral replication in maintaining HIV control and identify key biomarkers that predict viral load surges. - Source: PubMed
Publication date: 2026/01/22
Vadaq NadiraGroenendijk Albert LDos Santos Jéssica CMehta KavitaWit Ferdinand W N MVos Wilhelm A J WBlaauw Martinus J Tvan Eekeren Louise ELambrechts LaurensRutsaert SofieNelwan Erni JXu Cheng-JianJoosten Leo A Bde Mast QuirijnMatzaraki Vasilikivan Lunzen JanRokx CasperVerbon AnneliesNetea Mihai GVandekerckhove Linosvan der Ven André J A M - The gut microbiota plays an essential role in mucosal immunity, with secretory immunoglobulin A (IgA) acting as a key effector in neutralizing pathogens and maintaining host-microbiota homeostasis. IgA production occurs via T cell-dependent (TD) and -independent pathways, with T follicular helper (Tfh) cells driving high-affinity, antigen-specific IgA responses. However, the specific microbial taxa and metabolites that regulate Tfh-mediated IgA responses under steady-state conditions remain poorly understood. This study investigated how gut microbiota-derived signals shape Tfh responses and IgA production, with implications for enhancing mucosal vaccine efficacy. - Source: PubMed
Publication date: 2026/01/21
Ko HaeunKim Chan JohngChoi SeungyeonNoh JaegyunKim Seung WonLee JuhunByun SeohyunLee HaenaPark John ChulhoonPark Hye EunSharma AmitPark MinhyukPark JunghwanLee Choong-GuCha Kwang HyunIm Sin-Hyeog - The SAP-SLAM receptor system plays a critical role in immune regulation, with SAP deficiency leading to apoptosis resistance in T cells and disrupting immune homeostasis, as seen in XLP-1. This disorder, characterized by uncontrolled lymphoproliferation, often presents with a variable clinical spectrum. - Source: PubMed
Publication date: 2025/06/25
Zea-Vera Andrés FGiraldo-Ocampo SebastiánFernandes-Pineda MónicaBonelo-Perdomo AnilzaKang Elizabeth M - Clinical laboratories searching for pathogenic variants focus mostly on the protein-coding region and corresponding essential splicing sites. Screening for variants in intronic regions requires dedicated bioinformatics tools and detailed experimental studies to confirm deleteriousness and pathogenicity. We report intronic variants in a cohort of eight patients from seven kindreds with unexplained inborn errors of immunity (IEI). Using ad hoc bioinformatics tools, we identified seven kindreds carrying three branchpoint variants at three loci (, , and ) and four AG-gain acceptor site variants at another three loci (, , , and ). The variants were located between positions -9 and -49 relative to the wild-type acceptor site. The deleteriousness and, thus, pathogenicity of these variants were confirmed by exon-captured transcriptome studies and flow cytometry analyses of protein production or function. Our findings indicate that intronic variants should be systematically screened and investigated, even in clinical laboratory settings. - Source: PubMed
Publication date: 2025/07/17
Alioua NajibaLambert NathaliePuel MathildeHanein SylvainBastard PaulFusaro MathieuJaffray MarieMedel BernarditaKhellaf LydiaSeeleuthner YoannPerin MélodieJacques CorinnePasquet MarlèneOlivier LauraSepulveda FernandoLe Voyer TomCobat AurélieNitschké PatrickGalicier LionelSchleinitz NicolasOksenhendler EricMalphettes MarionNeven BénédicteMoshous DespinaSuarez FelipeFieschi ClaireCasanova Jean-Laurentde Saint Basile GenevièveDorval GuillaumePicard CapucineBustamante JacintaZhang PengRosain Jérémie