---
title: "Causal CD40 Allele (rs1883832) Reveals Context-Specific Trans-Effects in B Cells"
id: "biorxiv-0-identifying-the-causal-allele-in-the-cd40-autoimmune-locus-enables-discovery-of"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-0-identifying-the-causal-allele-in-the-cd40-autoimmune-locus-enables-discovery-of"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1?rss=1"
published_at: "2026-08-04T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Causal CD40 Allele (rs1883832) Reveals Context-Specific Trans-Effects in B Cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-0-identifying-the-causal-allele-in-the-cd40-autoimmune-locus-enables-discovery-of
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1?rss=1)
- **Published At:** 2026-08-04T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study used surface marker **CITE-seq** on 1,055,857 peripheral blood mononuclear cells (PBMCs) from 356 individuals to link genetics with immune cell surface proteins. - Genetic associations were defined for 148 surface proteins across eight immune cell types, focusing on signals relevant to autoimmune disease. - A signal at the **CD40** locus, previously implicated in rheumatoid arthritis (RA) and other autoimmune conditions, was detected; RA risk variants increased **CD40 protein** expression on B cells by ~20% with minimal effects on CD40 mRNA. - The authors applied base-resolution genome editing combined with multimodal single-cell readout (termed **CRAFT-seq**) to capture genomic sequence at edited sites and phenotypes at single-cell resolution. - Using CRAFT-seq, they identified a single causal allele, **rs1883832**, located within the Kozak motif of CD40. - Editing rs1883832 in primary B cells and profiling with CRAFT-seq revealed **trans-effects** on expression of more than 200 genes. - These trans-effects were context-specific: they were observed in a **light zone germinal center–like** state but were not detectable in population-scale datasets of unstimulated B cells. - The work establishes a framework to identify causal disease alleles and to discover their cis- and context-specific trans-effects through targeted editing and multimodal single-cell phenotyping. - The report is a preprint and has not undergone peer review; competing interests and funding sources are declared in the source.
## Clinical Analysis & Structured Key Points
[](https://www.biorxiv.org/cdn-cgi/content?id=5soC06q2vNgmY.g4IQS1bJCJcrNky_972h7OgAMQ0hY-1785922622.2922034-1.2.1.1-Eo.Pe6xq_NOl_qsERgVJzt6TO8dgBofuSs2_.uSK8pE) [Skip to main content](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1?rss=1#main-content) [![bioRxiv](https://www.biorxiv.org/sites/default/files/biorxiv_article_logo.jpg)](https://www.biorxiv.org/) * [Home](https://www.biorxiv.org/) * [Submit](https://www.biorxiv.org/submit-a-manuscript) * [FAQ](https://www.biorxiv.org/about/FAQ) * [Blog](https://connect.biorxiv.org/news/) * [ALERTS / RSS](https://www.biorxiv.org/content/alertsrss) * [Resources](https://connect.biorxiv.org/resources/) * [About](https://www.biorxiv.org/content/about-biorxiv) * [Channels](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1?rss=1) * [4D Nucleome](https://connect.biorxiv.org/relate/content/66) * [Academia Sinica](https://connect.biorxiv.org/group/content/38) * [Advances in Genome Biology and Technology (AGBT) General Meeting 2016 #AGBT16](https://connect.biorxiv.org/relate/content/10) * [Albert Einstein College of Medicine](https://connect.biorxiv.org/group/content/4) * [Aligning Science Across Parkinson's (ASAP)](https://connect.biorxiv.org/relate/content/195) * [Allen Institute for Cell Science](https://connect.biorxiv.org/relate/content/71) * [Arc Institute](https://connect.biorxiv.org/relate/content/224) * [Babraham Institute](https://connect.biorxiv.org/relate/content/197) * [BICCN/BICAN](https://connect.biorxiv.org/relate/content/208) * [BioImaging North America](https://connect.biorxiv.org/relate/content/194) * [Biology of Genomes 2016 #BOG16](https://connect.biorxiv.org/relate/content/19) * [Breakthrough Discoveries for Thriving with Bipolar Disorder](https://connect.biorxiv.org/relate/content/236) * [Brown University](https://connect.biorxiv.org/group/content/9) * [California Institute of Technology](https://connect.biorxiv.org/group/content/32) * [Carnegie Mellon University](https://connect.biorxiv.org/group/content/19) * [Case Western Reserve University](https://connect.biorxiv.org/group/content/36) * [Central Oxford Structural Microscopy and Imaging](https://connect.biorxiv.org/relate/content/143) * [Centre for Microbiology and Environmental Systems Science](https://connect.biorxiv.org/relate/content/190) * [Chan Zuckerberg Biohub](https://connect.biorxiv.org/relate/content/121) * [Columbia University](https://connect.biorxiv.org/group/content/27) * [Donders Institute for Brain, Cognition and Behaviour](https://connect.biorxiv.org/relate/content/184) * [DREAM](https://connect.biorxiv.org/relate/content/153) * [Drug Development and Clinical Therapeutics](https://connect.biorxiv.org/relate/content/52) * [ENCODE](https://connect.biorxiv.org/relate/content/177) * [Ernst Strüngmann Institute (ESI) for Neuroscience](https://connect.biorxiv.org/relate/content/211) * [European Molecular Biology Laboratory (EMBL)](https://connect.biorxiv.org/relate/content/159) * [Francis Crick Institute](https://connect.biorxiv.org/relate/content/88) * [Fred Hutchinson Cancer Center](https://connect.biorxiv.org/group/content/28) * [Georgia Institute of Technology](https://connect.biorxiv.org/group/content/20) * [Harvard Program in Therapeutic Sciences](https://connect.biorxiv.org/relate/content/151) * [The Howard Hughes Medical Institute (HHMI)](https://connect.biorxiv.org/relate/content/227) * [Human Cell Atlas](https://connect.biorxiv.org/relate/content/163) * [Human Pangenome Reference Consortium (HPRC)](https://connect.biorxiv.org/relate/content/215) * [IMO Workshop](https://connect.biorxiv.org/relate/content/8) * [Impact of Genomic Variation on Function (IGVF)](https://connect.biorxiv.org/relate/content/214) * [Institut Pasteur](https://connect.biorxiv.org/relate/content/235/channel) * [Institute of Science and Technology Austria](https://connect.biorxiv.org/group/content/12) * [International Human Epigenome Consortium (IHEC)](https://connect.biorxiv.org/relate/content/219) * [International Mouse Phenotyping Consortium (IMPC)](https://connect.biorxiv.org/relate/content/185) * [Iowa State University](https://connect.biorxiv.org/group/content/6) * [Johns Hopkins University](https://connect.biorxiv.org/group/content/47) * [Mathematical Oncology](https://connect.biorxiv.org/relate/content/1) * [Micron Oxford](https://connect.biorxiv.org/relate/content/116) * [Michigan State University](https://connect.biorxiv.org/group/content/7) * [Morgridge Institute](https://connect.biorxiv.org/group/content/57) * [National Taiwan University](https://connect.biorxiv.org/group/content/39) * [NCI Cancer Systems Biology Consortium](https://connect.biorxiv.org/relate/content/210) * [NF Open Science Initiative](https://connect.biorxiv.org/relate/content/213) * [NCI Human Tumor Atlas Network](https://connect.biorxiv.org/relate/content/171) * [Neuromatch Conference](https://connect.biorxiv.org/relate/content/209) * [NeurotechEU](https://connect.biorxiv.org/relate/content/189) * [North Carolina State University](https://connect.biorxiv.org/group/content/37) * [Northeastern University](https://connect.biorxiv.org/group/content/54) * [Oregon Health & Sciences University](https://connect.biorxiv.org/group/content/22) * [RNA Therapeutics Institute at UMass Chan Med School](https://connect.biorxiv.org/relate/content/243) * [Rosetta Commons](https://connect.biorxiv.org/relate/content/191) * [Rutgers University](https://connect.biorxiv.org/group/content/31) * [SeroNet](https://connect.biorxiv.org/relate/content/192) * [Simons Foundation Autism Research Initiative (SFARI)](https://connect.biorxiv.org/relate/content/74) * [Society for Molecular Biology and Evolution #SMBE2016](https://connect.biorxiv.org/relate/content/29) * [Somatic Cell Genome Editing Program](https://connect.biorxiv.org/relate/content/167) * [Somatic Mosaicism across the Human Tissues Network](https://connect.biorxiv.org/relate/content/222) * [SPARC](https://connect.biorxiv.org/relate/content/187) * [Stowers Institute for Medical Research](https://connect.biorxiv.org/group/content/3) * [Stockholm University](https://connect.biorxiv.org/group/content/14) * [Tel Aviv University](https://connect.biorxiv.org/group/content/8) * [The Michael J. Fox Foundation](https://connect.biorxiv.org/relate/content/207) * [The Rockefeller University](https://connect.biorxiv.org/group/content/2) * [The Sainsbury Laboratory](https://connect.biorxiv.org/relate/content/98) * [The Whitehead Institute](https://connect.biorxiv.org/relate/content/212) * [University of Connecticut Health Center](https://connect.biorxiv.org/group/content/16) * [University of California, Berkeley](https://connect.biorxiv.org/group/content/13) * [University of California, San Diego](https://connect.biorxiv.org/group/content/41) * [University of California, San Francisco](https://connect.biorxiv.org/group/content/10) * [University of Chicago](https://connect.biorxiv.org/group/content/42) * [University of Geneva](https://connect.biorxiv.org/group/content/26) * [University of Guelph](https://connect.biorxiv.org/group/content/23) * [University of Hong Kong](https://connect.biorxiv.org/group/content/29) * [University of Illinois Chicago](https://connect.biorxiv.org/group/content/43) * [University of Iowa](https://connect.biorxiv.org/group/content/24) * [University of Kansas](https://connect.biorxiv.org/group/content/33) * [University of Massachusetts Chan Medical School](https://connect.biorxiv.org/group/content/44) * [University of New South Wales](https://connect.biorxiv.org/group/content/25) * [University of Ottawa](https://connect.biorxiv.org/group/content/35) * [University of Sydney](https://connect.biorxiv.org/group/content/50) * [Vanderbilt University](https://connect.biorxiv.org/group/content/30) * [Vienna BioCenter](https://connect.biorxiv.org/relate/content/186) * [Washington University in St. Louis](https://connect.biorxiv.org/group/content/11) * [Weizmann Institute of Science](https://connect.biorxiv.org/group/content/15) * [Yale University](https://connect.biorxiv.org/group/content/53) Search for this keyword [Advanced Search](https://www.biorxiv.org/search) New Results Follow this preprint # Identifying the causal allele in the CD40 autoimmune locus enables discovery of context-specific trans-effects in B cells [ View ORCID Profile](http://orcid.org/0000-0002-1661-0941)Yoshihiko Tomofuji, [ View ORCID Profile](http://orcid.org/0000-0002-7717-3247)Zepeng Mu, Hafsa Mire, Yu Zhao, Cassidy Liu, Vidya Jayanthi, [ View ORCID Profile](http://orcid.org/0009-0001-7036-8375)Nicholas Sugiarto, Accelerating Medicines Partnership: RA/SLE Network, [ View ORCID Profile](http://orcid.org/0000-0002-5556-4618)Jeffrey A Sparks, [ View ORCID Profile](http://orcid.org/0000-0002-1901-8265)Soumya Raychaudhuri doi: https://doi.org/10.64898/2026.07.29.741564 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Yoshihiko Tomofuji 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yoshihiko%2BTomofuji%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Tomofuji%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYoshihiko%2BTomofuji%2B) * [ORCID record for Yoshihiko Tomofuji](http://orcid.org/0000-0002-1661-0941 "Open in new tab") Zepeng Mu 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zepeng%2BMu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mu%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZepeng%2BMu%2B) * [ORCID record for Zepeng Mu](http://orcid.org/0000-0002-7717-3247 "Open in new tab") Hafsa Mire 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Hafsa%2BMire%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mire%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHafsa%2BMire%2B) Yu Zhao 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yu%2BZhao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zhao%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYu%2BZhao%2B) Cassidy Liu 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Cassidy%2BLiu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liu%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACassidy%2BLiu%2B) Vidya Jayanthi 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Vidya%2BJayanthi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Jayanthi%20V&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AVidya%2BJayanthi%2B) Nicholas Sugiarto 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Nicholas%2BSugiarto%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sugiarto%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANicholas%2BSugiarto%2B) * [ORCID record for Nicholas Sugiarto](http://orcid.org/0009-0001-7036-8375 "Open in new tab") Jeffrey A Sparks 1 Brigham and Women's Hospital; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jeffrey%2BA%2BSparks%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sparks%20JA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJeffrey%2BA%2BSparks%2B) * [ORCID record for Jeffrey A Sparks](http://orcid.org/0000-0002-5556-4618 "Open in new tab") Soumya Raychaudhuri 2 Broad Institute * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Soumya%2BRaychaudhuri%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Raychaudhuri%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASoumya%2BRaychaudhuri%2B) * [ORCID record for Soumya Raychaudhuri](http://orcid.org/0000-0002-1901-8265 "Open in new tab") * For correspondence: soumya@broadinstitute.org * [Abstract](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5679921/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5679921/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5679921/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5679921/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5679921/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Thousands of genetic variants are associated with autoimmune diseases, but causal variants, their mechanisms, and the pathogenic context in which they act are elusive. Knowledge of pathogenic contexts may enable effective targeted therapies, instead of broad immunosuppressive approaches. First, to focus on the genetics of immune response, we used surface marker CITE-seq data from 1,055,857 peripheral blood mononuclear cells from 356 individuals. We defined genetic associations to 148 surface proteins across eight cell types. We observed a signal in the CD40 locus, implicated in rheumatoid arthritis (RA) and other autoimmune conditions. RA risk variants increased CD40 protein expression by ~20% on B cells, but with minimal mRNA effects. Second, we deployed base-resolution genome editing, with CRAFT-seq, capturing genomic DNA sequence at the edited site and multimodal phenotypes at single-cell resolution. We defined a single causal allele, rs1883832, within the Kozak motif. Third, we edited this allele, in primary B cells and conducted CRAFTseq to demonstrate trans-effects in >200 genes. These effects were only in the light zone germinal center-like state. Importantly, these trans-effects were not seen in population-scale cohorts of unstimulated B cells. This represents a framework to define disease causal alleles, their cis- and trans-effects. It demonstrates the power of defining causal genetic variation to find trans-effects through editing, which cannot easily be found in population studies. ### Competing Interest Statement J.A.S has received research support from 10x Genomics, Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, and Sonoma Biotherapeutics unrelated to this work. He has performed consultancy for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, First Tracks, GSK, Immunovant, Invivyd, Johnson & Johnson, Novartis, Pfizer, Sun, and UCB unrelated to this work. S.R. is a founder for Mestag, Inc, on advisory boards for Pfizer, Janssen and BMS, and a consultant for Abbvie, Biogen, and Merck. ## Funder Information Declared NIH Common Fund, 2P01AI148102 5R01HG013083, 5U01HG012009, 5R01AR063759 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1?rss=1#page) [ Previous](https://www.biorxiv.org/content/10.64898/2026.07.30.741804v1 "Effects of transcranial focused ultrasound stimulation to human lateral geniculate nucleus on visual perception and steady-state visual evoked potentials") Posted August 04, 2026. [ Download PDF](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/08/04/2026.07.29.741564.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.07.29.741564v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Identifying the causal allele in the CD40 autoimmune locus enables discovery of context-specific trans-effects in B cells Yoshihiko Tomofuji, Zepeng Mu, Hafsa Mire, Yu Zhao, Cassidy Liu, Vidya Jayanthi, Nicholas Sugiarto, Accelerating Medicines Partnership: RA/SLE Network, Jeffrey A Sparks, Soumya Raychaudhuri bioRxiv 2026.07.29.741564; doi: https://doi.org/10.64898/2026.07.29.741564 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Share This Article: Copy [![Twitter logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/twitter.png)](https://www.biorxiv.org/highwire_log/share/twitter?link=http%3A%2F%2Ftwitter.com%2Fshare%3Furl%3Dhttps%253A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.64898%2F2026.07.29.741564v1%26text%3DIdentifying%2520the%2520causal%2520allele%2520in%2520the%2520CD40%2520autoimmune%2520locus%2520enables%2520discovery%2520of%2520context-specific%2520trans-effects%2520in%2520B%2520cells
## Related Clinical Research

- [Emergency diagnosis frequency and outcomes across 13 non-cancer conditions in England: analysis of](https://medichelpline.com/clinical-feed/plos-medicine-2-frequency-and-prognostic-outcomes-of-emergency-diagnosis-in-13-non-neoplastic.md)
- [Climate change worsens health for people with chronic illness](https://medichelpline.com/clinical-feed/stat-news-1-opinion-climate-change-is-making-people-with-chronic-illness-even-sicker.md)
- [ARID5B promotes transition from inflammatory to tissue‑destructive fibroblasts in arthritis](https://medichelpline.com/clinical-feed/biorxiv-1-arid5b-drives-an-inflammatory-to-destructive-shift-in-pathologic-fibroblast.md)
- [Bupropion Hydrochloride for Improving Recovery in Acute Ischaemic Stroke: BASE Trial Protocol](https://medichelpline.com/clinical-feed/bmj-open-4-protocol-for-base-a-multicentre-double-blind-randomised-controlled-trial-of.md)
- [Brief-COPE Questionnaire Shows Five-Factor Structure in Seropositive Rheumatoid Arthritis](https://medichelpline.com/clinical-feed/medrxiv-1-validation-of-the-brief-cope-questionnaire-in-a-seropositive-rheumatoid.md)

## Navigation
- [← Back to General Feed](https://medichelpline.com/clinical-feed/general.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.