Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 53 min ago
Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis

  • Alena I. Zagrebneva1,2
  • Elena N. Simonova2
  • Yuliya A. Gavrikova2,3
  • Vladislav V. Dolgov2,3
  • Anastasiia A. Buianova2,4
  • Ekaterina D. Glumova5
  • Maria I. Tubalova5
  • Galina S. Koksharova5
  • Artem R. Nurislamov5
  • Vadim I. Mazurov1,6
6 affiliations
  1. 1Organizational and Methodological Department, North-Western State Medical University Named After I.I. Mechnikov, 41, Kirochnaya St., Saint Petersburg 191015, Russia
  2. 2Moscow Clinical Research Center “Hospital No. 52”, 3, Pekhotnaya St., Moscow 123182, Russia
  3. 3Research Institute of Healthcare Organization and Medical Management, Moscow Department of Healthcare, 30, Bolshaya Tatarskaya St., Moscow 115184, Russia
  4. 4Russian Clinical Research Center of Gerontology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow 129226, Russia
  5. 5Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia
  6. 6Clinical Rheumatology Hospital No. 25 Named After V.A. Nasonova, 30, Bolshaya Podyacheskaya St., Saint Petersburg 190068, Russia
Read full textPDFDOICite

Abstract

Genetic determinants of response to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) remain insufficiently characterized. We developed a targeted sequencing panel of candidate immunogenetic variants identified through a literature review and evaluated associations with response to TNF-α inhibitors, response to IL-6 inhibitors, and difficult-to-treat RA (D2TRA). Whole-blood DNA was sequenced using custom hybridization capture on a DNBSEQ-G400 platform (2 × 150 bp). Reads were aligned to hg38 using BWA-MEM, and variants were called with GATK HaplotypeCaller. After quality control, the D2TRA analysis included 154 patients (59 D2TRA and 95 non-D2TRA); drug-response analyses included 66 anti-TNF patients (26 responders, 40 non-responders) and 69 anti-IL-6 patients (29 responders, 40 non-responders). Treatment-response associations were assessed using unadjusted allelic chi-square tests with multiple-testing correction; D2TRA was analyzed using logistic regression adjusted for age, sex, and body mass index. For IL-6 inhibitor response, rs11656130/MAP2K6 (p = 0.0163; FDR = 0.3704) and rs4910008/GALNT18 (p = 0.0212; FDR = 0.3704) were identified, while rs7767069/LINC02549 was associated with TNF-α inhibitor response (p = 0.0171; FDR = 0.5968). For D2TRA, rs1813443 in CNTN5 (OR = 1.85, p = 0.017) and rs12081765, an intergenic variant near LMX1A/RXRG (OR = 0.59, p = 0.028), were nominally associated; neither association remained significant after multiple-testing correction. With the current sample sizes, the study could detect only large genetic effects, and was underpowered for these after Bonferroni correction (α = 0.00143). The findings highlight the limited reproducibility of candidate pharmacogenetic markers in RA and provide a targeted panel and analytical framework for larger replication studies.

Related

  1. Integrating bulk and single-cell RNA sequencing to identify mitochondrial quality control-related key genes in rheumatoid arthritis
    Yuting Xiao, Jiayou zhang, Jing Su +1
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textGeneral medicineCrossref
  2. A Preliminary Exploratory Study Based on LC–MS/MS and LFQ for Candidate Protein Biomarkers in Peripheral Blood from Rheumatoid Arthritis
    Maria P. Toussaint-Padilla, Sherine Gabriel, Timothy L. Karr +4
    BiomedicinesPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. Predictive biomarkers for precision treatment in rheumatoid arthritis: are we there yet?
    Jianyang Liu, Per-Johan Jakobsson
    Frontiers in pharmacologyPeer-reviewedCC BYFull textPharmacology & toxicologyEurope PMC
  4. Successful Treatment of Recalcitrant Pyoderma Gangrenosum with Baricitinib in Two Patients with Rheumatoid Arthritis.
    Christian Ciolfi, Bernd Raffeiner, Margherita Zen +3
    Dermatology practical & conceptualPeer-reviewedCC BY-NCFull textEpidemiology & public healthEurope PMC
  5. Integrative analysis reveals shared biomarkers and pathways in osteoporosis and rheumatoid arthritis using machine learning and single-cell sequencing
    Jin Zhao, Yixuan Chen, Fei Yang +6
    PLOS OnePeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCell biologyPLOSPMC

Cite

BibTeXRIS
BibTeX
@article{zagrebneva2026targeted,
  title = {{Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis}},
  author = {Alena I. Zagrebneva and Elena N. Simonova and Yuliya A. Gavrikova and Vladislav V. Dolgov and Anastasiia A. Buianova and Ekaterina D. Glumova and Maria I. Tubalova and Galina S. Koksharova and Artem R. Nurislamov and Vadim I. Mazurov},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198800},
  url = {https://www.mdpi.com/1422-0067/27/19/8800},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis
AU  - Alena I. Zagrebneva
AU  - Elena N. Simonova
AU  - Yuliya A. Gavrikova
AU  - Vladislav V. Dolgov
AU  - Anastasiia A. Buianova
AU  - Ekaterina D. Glumova
AU  - Maria I. Tubalova
AU  - Galina S. Koksharova
AU  - Artem R. Nurislamov
AU  - Vadim I. Mazurov
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27198800
UR  - https://www.mdpi.com/1422-0067/27/19/8800
AB  - Genetic determinants of response to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) remain insufficiently characterized. We developed a targeted sequencing panel of candidate immunogenetic variants identified through a literature review and evaluated associations with response to TNF-α inhibitors, response to IL-6 inhibitors, and difficult-to-treat RA (D2TRA). Whole-blood DNA was sequenced using custom hybridization capture on a DNBSEQ-G400 platform (2 × 150 bp). Reads were aligned to hg38 using BWA-MEM, and variants were called with GATK HaplotypeCaller. After quality control, the D2TRA analysis included 154 patients (59 D2TRA and 95 non-D2TRA); drug-response analyses included 66 anti-TNF patients (26 responders, 40 non-responders) and 69 anti-IL-6 patients (29 responders, 40 non-responders). Treatment-response associations were assessed using unadjusted allelic chi-square tests with multiple-testing correction; D2TRA was analyzed using logistic regression adjusted for age, sex, and body mass index. For IL-6 inhibitor response, rs11656130/MAP2K6 (p = 0.0163; FDR = 0.3704) and rs4910008/GALNT18 (p = 0.0212; FDR = 0.3704) were identified, while rs7767069/LINC02549 was associated with TNF-α inhibitor response (p = 0.0171; FDR = 0.5968). For D2TRA, rs1813443 in CNTN5 (OR = 1.85, p = 0.017) and rs12081765, an intergenic variant near LMX1A/RXRG (OR = 0.59, p = 0.028), were nominally associated; neither association remained significant after multiple-testing correction. With the current sample sizes, the study could detect only large genetic effects, and was underpowered for these after Bonferroni correction (α = 0.00143). The findings highlight the limited reproducibility of candidate pharmacogenetic markers in RA and provide a targeted panel and analytical framework for larger replication studies.
SN  - 1422-0067
ER  -