Abstract

BackgroundAnalyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered burdensome, although patients do not always consider invasive methods as a high burden. We aimed to investigate the perspectives of study participants undergoing ultrasound-guided inguinal lymph node (LN) needle biopsy sampling and determine the molecular and cellular quantity and quality of LN biopsies.MethodsTogether with patient research partners, questionnaires were developed to evaluate the motives, expectations, and experiences of participants undergoing a LN biopsy. Healthy controls and RA(-risk) patients were asked to complete these questionnaires before and after the procedure. RNA and lymphocyte yields from obtained LN biopsies were also calculated.ResultsWe included 50 individuals, of which 43 (86%) reported their pre- and post-procedure experiences. The median reported pain on a 5-point Likert scale (1 not to 5 very painful) was 1. Interestingly, almost all (n = 32; 74%) study participants would undergo a second procedure and more than half (n = 23; 54%) would encourage others to take part in the LN biopsy study. Motives for current and future participation were mostly altruistic. Inguinal hematoma occurred frequently, but no other significant or unexpected complications ensued. The LN biopsies yielded sufficient and high-quality RNA and lymphocyte numbers.ConclusionsUltrasound-guided inguinal LN biopsy sampling is well-tolerated, safe, and provides sufficient material for further molecular and cellular analyses. Our participants’ positive experiences endorse the application of this research tool to further elucidate the pathogenesis of RA and other inflammatory diseases.

Highlights

  • Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA)

  • We previously discovered through ultrasound-guided lymph node (LN) biopsy sampling that, compared to healthy controls (HCs), multiple LN alterations can be found in At risk of developing rheumatoid arthritis (RA-risk) individuals [7, 14,15,16], which highlights the potential of this technique to study the preclinical or “at-risk” phase of RA

  • To validate that ultrasound-guided LN biopsy sampling can be applied safely in immune-mediated inflammatory diseases (IMIDs) research studies, we investigated the experiences of HCs, individuals at risk of developing RA, and RA patients undergoing the procedure

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Summary

Introduction

Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Loss of peripheral tolerance is associated with the development of immune-mediated inflammatory diseases (IMIDs), like RA, due to the occurrence of activated auto-reactive immune cells and auto-antibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA) [6] These auto-antibodies can already be present years before the onset of RA [7] in the so-called RA-risk individuals [6, 8, 9]. Ultrasound-guided LN biopsy sampling allows for detailed cellular and molecular studies of the immune system beyond the peripheral blood compartment at all disease stages This may further elucidate RA pathogenesis and identify novel targets: prognostic and/ or therapeutic biomarkers, which could be involved in clinical decision-making for personalized treatment, biomarkers that may identify persons that will develop RA or possibly other IMIDs, and biomarkers that may be targeted to prevent disease. The latter two are very important in the quest towards disease prevention [18]

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