TY - JOUR
T1 - The germinal center milieu in rheumatoid arthritis
T2 - The immunological drummer or dancer?
AU - Anang, Dornatien C.
AU - Balzaretti, Giulia
AU - van Kampen, Antoine
AU - de Vries, Niek
AU - Klarenbeek, Paul L.
N1 - Funding Information: Funding: This research was funded by COSMIC (www.cosmic-h2020.eu, https://www.cosmic-h2020.eu/ accessed on 28 September 2021) which has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 765158. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflam-mation, affecting approximately 1% of the general population. To alleviate symptoms and amelio-rate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment.
AB - Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflam-mation, affecting approximately 1% of the general population. To alleviate symptoms and amelio-rate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment.
KW - Autoantibodies
KW - Follicular T cells
KW - Germinal centers
KW - Lymphoid organs
KW - Rheumatoid Arthritis
UR - http://www.scopus.com/inward/record.url?scp=85116009374&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms221910514
DO - https://doi.org/10.3390/ijms221910514
M3 - Review article
C2 - 34638855
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 10514
ER -