Page 21 - ITPS-8-1

INNOSC Theranostics and
Pharmacological Sciences Transcriptome-based RNA sequencing

affect larger joints such as the knees and shoulders. Increased An attribute of RA is the presence of immune
stiffness in the morning is a prominent symptom of this complexes in the synovial fluid, which are composed of
condition, and these symptoms become more noticeable bonded antibodies that increase inflammation. All these
after extended periods of inactivity. RA-related pain is cells release cytokines, which aid in increasing capillary
1-3
categorized as nociceptive rather than neuropathic because permeability and adhesion molecule expression on the
it originates at the site of inflammation. As the pathological vascular vasculature, enabling immune cells to travel into
state worsens, continued inflammation causes tendon the joint and induce RA, as shown in Figure 2. 9
binding, erosion, and degradation of the articular surface; RA can be caused by factors such as smoking, heredity,
this can limit the range of motion and cause deformity and the bacterium Porphyromonas gingival that causes
and local osteoporosis, which frequently develops around gingivitis. These factors can alter autoantigens, resulting
the inflamed joints of patients with RA. Rheumatoid and in joint inflammation and cytokines. Antigen-presenting
4
musculoskeletal disorders represent a significant global cells recognize this change and initiate an immune
economic burden, and their prevalence is increasing response. CD4 T-cell activation triggers B-cell activation
because of changes in behavior and population; among in the germinal center, leading to the formation of plasma
them, RA is the most prevalent inflammatory arthritis. cells that generate autoantibodies against the body’s own
As these disorders cause more functional impairments in antigen.
adults than any other ailments, they are considered the
primary cause of disability and early retirement among An important component of RA is antibodies.
workers. Therefore, early identification and individualized, Rheumatoid factor IgM antibody targets the Fc region
cell-specific therapies are essential for the management of of IgG and is present in 75% of patients with RA, as well
RA. 5 as anticitrullinated protein antibodies, which target
citrullinated proteins such as fibrin and filaggrin. These
1.1. Pathophysiology of RA antibodies also cause inflammation and synovial fluid
In RA, the synovium is essentially inflamed, which causes deposition. Proteins in which their arginine residues are
erosion of the bone and cartilage, as depicted in Figure 1. citrullinated are known as citrullinated proteins. After
Although the precise cause of the inflammation remains the attack, the body targets this protein, recognizes it as a
unknown, macrophages, which are often found in the foreign particle, and begins to attack, causing swelling and
5
synovium, are known to secrete cytokines such as tumor inflammation.
necrosis factor-α, interleukin-1, and interleukin-6, which 1.2. Clinical manifestation
cause inflammation. These cytokines stimulate fibroblast-
like synoviocytes (synovial intimal cells are believed to RA is a symmetrical arthritic joint with pain, swelling,
be in charge of producing synovial fluid components), and nodules. Early symptoms affect the hand, particularly
which start multiplying upon activation. Simultaneously, the proximal and metacarpal phalangeal joints. As the
6
synoviocytes support the expression of RANKL (osteoclast disease worsens, additional hand characteristics such
as swan neck, Boutonniere, and thumb Z deformity
differentiation factor), which, in conjunction with
cytokines, increases osteoclast activity (bone degradation), appear. Angiogenesis, the expansion of blood vessels
ultimately resulting in bone erosion. Proteases are secreted from pre-existing vasculature, is also observed in patients
7
by activated, proliferating synovial cells and tissues with RA.
similar to fibroblasts. These proteases lead to cartilage 2. Overview of transcriptomics:
deterioration or breakdown. Activation of fibroblast-like Understanding RNA sequencing (RNA-seq)
synoviocytes results in symmetrical arthritis. T cells can
release interleukin-17, which activates fibroblast-like technologies
synoviocytes and increases macrophage activity; moreover, Genomes in organisms are composed of DNA and genes,
these cells induce inflammation. Furthermore, T cells aid which remain almost identical in all cells. Nevertheless,
8
in the expression of RANKL, which activates osteoclasts to when an organism experiences specific environmental
cause bone degradation. Moreover, plasma cells are present changes, its cells must decode this genomic information
in this region; although plasma cells constitute only 5% differentially. This information is translated into RNA,
of the overall immune cells, they support inflammation which is used to produce proteins. The transcriptome is a
by producing cytokines and antibodies. Neutrophils are complete set of messenger RNA (mRNA) transcribed in a
also present in the synovial fluid and secrete proteases cell at a specific time, expressing a part of the functional
and reactive oxygen species, which degrade cartilage and genome. Transcriptomic studies examine the transcriptome
bone. 5,8 using various techniques. 10

Volume 8 Issue 1 (2025) 15 doi: 10.36922/itps.4449