scholarly journals Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

2022 ◽  
Vol 8 ◽  
Author(s):  
Aoife M. O'Byrne ◽  
Tineke A. de Jong ◽  
Lisa G. M. van Baarsen
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Peripheral Tolerance ◽  
Unknown Etiology ◽  
Synovial Joint ◽  
Innovative Drug

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

scholarly journals Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis

2020 ◽  
Vol 21 (16) ◽  
pp. 5713
Author(s):  
Janine S. Hähnlein ◽  
Reza Nadafi ◽  
Tineke A. de Jong ◽  
Johanna F. Semmelink ◽  
Ester B. M. Remmerswaal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Antigen Presentation ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
Interferon Γ ◽  
Peripheral Tolerance ◽  
Lymph Node Stromal Cells

Background: In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) maintain peripheral tolerance through presentation of peripheral tissue antigens (PTAs). We hypothesize that dysregulation of peripheral tolerance mechanisms in human LNSCs might underlie pathogenesis of RA. Method: Lymph node (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive for RA-associated autoantibodies but without clinical disease (RA-risk individuals), and 14 seronegative healthy individuals. Ex vivo human LNs from non-RA individuals were used to directly analyze stromal cells. Molecules involved in antigen presentation and immune modulation were measured in LNSCs upon interferon γ (IFNγ) stimulation (n = 15). Results: Citrullinated targets of ACPAs were detected in human LN tissue and in cultured LNSCs. Human LNSCs express several PTAs, transcription factors autoimmune regulator (AIRE) and deformed epidermal autoregulatory factor 1 (DEAF1), and molecules involved in citrullination, antigen presentation, and immunomodulation. Overall, no clear differences between donor groups were observed with exception of a slightly lower induction of human leukocyte antigen-DR (HLA-DR) and programmed cell death 1 ligand (PD-L1) molecules in LNSCs from RA patients. Conclusion: Human LNSCs have the machinery to regulate peripheral tolerance making them an attractive target to exploit in tolerance induction and maintenance.

scholarly journals Cervical lymph node enlargement as the initial manifestation of rectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tong-Hui Xie ◽  
Peng Su ◽  
Jian-Guo Hong ◽  
Hui Zhang
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cervical Lymph Node ◽  
Clinical Manifestations ◽  
Initial Symptom ◽  
Cervical Lymph Nodes ◽  
Supraclavicular Lymph Nodes ◽  
Lymph Node Enlargement

Abstract Background Colorectal cancer is a very common malignant tumor worldwide. The clinical manifestations of advanced colorectal cancer include the changes in bowel habits, hematochezia, diarrhea, local abdominal pain and other symptoms. However, the colorectal cancer with an initial symptom of cervical lymph node enlargement is extremely rare. In this article, we report a case of rectal cancer presenting with cervical lymph nodes enlargement as the initial symptom. Case presentation A 57-year-old woman was admitted to our hospital for cervical lymph node enlargement which was accidentally detected during physical examination. Computed tomography scan revealed multiple enlarged lymph nodes in the neck. Cervical ultrasound showed normal thyroid gland and multiple left supraclavicular lymph nodes enlargement. The patient underwent lymph nodes biopsy and pathologic results showed metastatic adenocarcinoma. The subsequent lower gastrointestinal endoscopy revealed a mucosal bulge lesion located at rectus and biopsy revealed adenocarcinoma. The patient underwent rectal cancer resection. She is alive with no evidence of recurrence or new tumors 2 years after surgery. Conclusions Cervical lymph node metastasis is a rare metastatic way in colorectal cancer. This is the first case of rectal cancer presenting with cervical lymph nodes metastases as the initial symptom. Surgical resection combined with postoperative chemotherapy improved long-term prognosis of the patient. This rare metastatic way of rectal cancer should be paid attention for clinicians.

scholarly journals From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 22 (2) ◽  
pp. 686
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Shue-Fen Luo ◽  
Jenn-Haung Lai
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Response To Therapy ◽  
Current Evidence ◽  
Prognosis Prediction ◽  
Diagnosis And Prognosis ◽  
Systemic Inflammatory Disease ◽  
Citrullinated Protein

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease mainly involving synovial inflammation and articular bone destruction. RA is a heterogeneous disease with diverse clinical presentations, prognoses and therapeutic responses. Following the first discovery of rheumatoid factors (RFs) 80 years ago, the identification of both anti-citrullinated protein antibodies (ACPAs) and anti-carbamylated protein antibodies (anti-CarP Abs) has greatly facilitated approaches toward RA, especially in the fields of early diagnosis and prognosis prediction of the disease. Although these antibodies share many common features and can function synergistically to promote disease progression, they differ mechanistically and have unique clinical relevance. Specifically, these three RA associating auto-antibodies (autoAbs) all precede the development of RA by years. However, while the current evidence suggests a synergic effect of RF and ACPA in predicting the development of RA and an erosive phenotype, controversies exist regarding the additive value of anti-CarP Abs. In the present review, we critically summarize the characteristics of these autoantibodies and focus on their distinct clinical applications in the early identification, clinical manifestations and prognosis prediction of RA. With the advancement of treatment options in the era of biologics, we also discuss the relevance of these autoantibodies in association with RA patient response to therapy.

OP0256 Changes of Microrna Expression in Lymph Node Stromal Cells of Rheumatoid Arthritis Patients

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 158.2-158
Author(s):  
C. Ospelt ◽  
J. Hähnlein ◽  
R.E. Gay ◽  
P.P. Tak ◽  
D.M. Gerlag ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Stromal Cells ◽  
Microrna Expression ◽  
Lymph Node Stromal Cells

scholarly journals OP0154 Altered lymph node stromal cells during the earliest phases of rheumatoid arthritis

2017 ◽  
Author(s):  
C Ospelt ◽  
E Karouzakis ◽  
J Hähnlein ◽  
JF Semmelink ◽  
RE Gay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Stromal Cells ◽  
Lymph Node Stromal Cells

scholarly journals T- and B cell clones circulate between synovial tissue and lymph node in early stages of rheumatoid arthritis (RA): elucidating the role of lymph nodes in RA

2011 ◽  
Vol 70 (Suppl 2) ◽  
pp. A57-A57
Author(s):  
P. L. Klarenbeek ◽  
M. J. de Hair ◽  
M. E. Doorenspleet ◽  
S. Alivernini ◽  
B. D. C. van Schaik ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Lymph Nodes ◽  
B Cell ◽  
Synovial Tissue ◽  
Early Stages ◽  
Cell Clones

scholarly journals The Results of Fetal Chondrocytes Transplantation in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 3 ◽  
Author(s):  
Natalya Krivoruchko ◽  
Saltanat Tuganbekova ◽  
Gulnar Rakhimbekova ◽  
Karlygash Kuzembaeva ◽  
Lina Zaripova
Keyword(s):  
Rheumatoid Arthritis ◽  
Morphological Changes ◽  
Control Cell ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Human Embryos ◽  
Control Group ◽  
X Ray ◽  
Donor Cells

Introduction. Nowadays anti-inflammatory and immunosuppressive therapy has significantly improved the quality of life and prognosis of rheumatoid arthritis (RA). Nevertheless, there are still many patients with progressive rheumatoid inflammation, resulting in the destruction of joints. Cell therapy seems like a promising direction in rheumatology. The aim of our research was to evaluate the efficacy of fetal chondrocyte transplantation in patients with RA.Methods. We examined 60 patients with rheumatoid arthritis (I - III stages) between 20 and 63 years of age. They were divided into 2 groups: the first group underwent the fetal chondrocytes transplantation (n = 40), and the second was a control group who got conservative therapy (n = 20). Donor cells were taken from the chondrogenic layer of the humerus or femur heads and hip condyles of human embryos in gestation for 17-20 weeks. A suspension of fetal chondrocytes injected into affected areas of the articular surfaces under X-ray control. Cell viability was determined before the injection. Efficacy of the therapy was assessed by clinical, instrumental, and laboratory tests. This clinical trial was allowed by The Ministry of Public Health and Ethics Committee. All of our patients gave informed consent for the fetal chondrocytes transplantation.Results. Evaluation of the clinical manifestations of RA in the first group of patients showed 3.7 times decrease in pain and 1.6 times relief of synovitis. Complete reduction of contracture was observed in 82% of patients in the first group. Morphometric changes in X-ray demonstrated inhibition of the destruction in articular cartilage and surfaces of bones after transplantation of fetal chondrocytes. The dynamics of morphological changes in synovium showed 2.5 times reduction of the inflammatory reaction. Transplantation of fetal chondrocytes led to a significant reduction in ESR, CRP, fibrinogen , γ-globulin after a period of 12 months (p < 0.03). Furthermore, patients in the second group had 2.7 times higher risk of ankylosis compared to the first group. We did not observe any complications of fetal chondrocytes transplantation.Conclusions. Application of fetal chondrocytes therapy had the desired clinical effect, which was confirmed by reduction of the RA activity and decrease of cartilage and bone destruction. 

scholarly journals Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis

2019 ◽  
Vol 10 ◽  
Author(s):  
Emmanuel Karouzakis ◽  
Janine Hähnlein ◽  
Cristoforo Grasso ◽  
Johanna F. Semmelink ◽  
Paul P. Tak ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Molecular Characterization ◽  
Stromal Cells ◽  
Human Lymph Node ◽  
Lymph Node Stromal Cells

scholarly journals Multifunctional Roles of Reticular Fibroblastic Cells: More Than Meets the Eye?

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
H. G. Alvarenga ◽  
L. Marti
Keyword(s):  
Immune Response ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Lymphoid Organ ◽  
Peripheral Tolerance ◽  
Structural Function ◽  
Cytokines And Chemokines ◽  
Functional Aspects ◽  
Reticular Cells ◽  
Fibroblastic Cells

Fibroblastic reticular cells (FRCs) are stromal cells found in secondary lymphoid organ. Despite its structural function in the lymph nodes being well established, recent studies indicate that the FRCs also play a key role in immunological processes, associated with cell transit, immune response, and cells activation quality, and contribute to peripheral tolerance. To this end, we focus this review on lymph nodes FRC characterization and discuss functional aspects such as production of cytokines and chemokines and their involvement in the immune response, seeking to establish whether certain subsets have a more functional specialization.

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