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IMMUNOLOGICAL ASPECTS OBSERVED IN PATIENTS WITH STAGE 3-4
COXARTHROSIS
Khamroyev Shakhboz Barotovich
Radiologist at TISU MEDHUB Multidisciplinary Clinic
Rakhmanova Sanobar Sabirovna
Head of Department, Associate Professor
Tashkent Medical Academy, Urgench Branch
Abstract:
Coxarthrosis (hip osteoarthritis) is a chronic degenerative joint disease that, in
stages III–IV, is characterized not only by mechanical destruction of cartilage and bone but
also by significant immunological alterations. Elevated pro-inflammatory cytokines,
activation of macrophages and lymphocytes, as well as systemic immune imbalance, play an
important role in disease progression. Recognition of these immunological aspects may
contribute to the development of new diagnostic markers and targeted therapies.
Keywords:
Coxarthrosis, hip osteoarthritis, immunology, cytokines, advanced stages.
Annotatsiya:
Koksartroz (son artrozi) — bo‘g‘imning surunkali degenerativ kasalligi bo‘lib,
III–IV bosqichlarda nafaqat tog‘ay va suyakning mexanik yemirilishi, balki sezilarli
immunologik oʻzgarishlar bilan ham namoyon bo‘ladi. Sitokinlar darajasining ortishi,
makrofag va limfotsitlarning faollashuvi hamda umumiy immun muvozanatning buzilishi
kasallik rivojlanishida muhim rol oʻynaydi. Ushbu immunologik jihatlarni o‘rganish yangi
diagnostik markerlar va maqsadli terapiyalarni ishlab chiqishda yordam berishi mumkin.
Kalit so‘zlar:
Koksartroz, son artrozi, immunologiya, sitokinlar, kech bosqichlar.
Аннотация:
Коксартроз (тазобедренный остеоартроз) — хроническое дегенеративное
заболевание сустава, которое на III–IV стадиях характеризуется не только
механическим разрушением хряща и кости, но и выраженными иммунологическими
изменениями. Повышение уровня провоспалительных цитокинов, активация
макрофагов и лимфоцитов, а также системный иммунный дисбаланс играют важную
роль в прогрессировании болезни. Изучение этих иммунологических аспектов может
способствовать разработке новых диагностических маркеров и таргетной терапии.
Ключевые слова:
Коксартроз, остеоартроз тазобедренного сустава, иммунология,
цитокины, поздние стадии.
Coxarthrosis, also known as hip osteoarthritis, is one of the most prevalent degenerative
joint diseases worldwide and represents a major cause of chronic pain, disability, and
reduced quality of life among the elderly population. It is characterized by progressive
destruction of the articular cartilage, remodeling of the subchondral bone, osteophyte
formation, and varying degrees of synovial inflammation. Traditionally, coxarthrosis has
been considered primarily a “wear-and-tear” disease, attributed to mechanical overload,
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aging, obesity, and joint malformations. However, increasing evidence suggests that
immune-mediated mechanisms play a central role in both the initiation and progression of
the disease, particularly in advanced stages (stage III–IV). In recent decades, a paradigm
shift has occurred in the understanding of osteoarthritis pathogenesis. Rather than being
viewed solely as a mechanical disorder, coxarthrosis is now recognized as a complex,
multifactorial disease in which biomechanical, metabolic, and immunological factors
interact. Advanced imaging and molecular studies have revealed that even in late stages,
where structural damage is most evident, persistent low-grade inflammation contributes
significantly to cartilage degradation, pain sensitization, and disease progression.
Immunological aspects of coxarthrosis involve both innate and adaptive immune responses.
Pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-alpha
(TNF-α), and interleukin-6 (IL-6) are elevated in the synovial fluid and serum of patients
with advanced disease, driving catabolic processes within the joint. Activation of synovial
macrophages and infiltration of T lymphocytes further amplify the inflammatory cascade.
Moreover, the imbalance between pro-inflammatory and anti-inflammatory mediators,
combined with impaired regulatory T-cell activity, contributes to the chronicity of
inflammation and irreversible joint damage. From a clinical perspective, recognition of the
immunological component of coxarthrosis is of great importance. It opens new opportunities
for early diagnosis, prognostic assessment, and the development of targeted therapies aimed
not only at symptom control but also at modifying disease progression. While current
management strategies rely heavily on analgesics, physiotherapy, and surgical interventions
such as total hip arthroplasty, future therapeutic approaches may benefit from the
modulation of immune pathways, including cytokine inhibition and immunoregulatory
strategies. Therefore, studying the immunological aspects in patients with stage III–IV
coxarthrosis is essential for a deeper understanding of disease mechanisms and for
improving patient care. This paper aims to review and analyze the immune alterations
observed in late-stage coxarthrosis and their potential implications for clinical practice.
Study design and patients: This study was conducted as a cross-sectional clinical and
laboratory investigation. A total of 60 patients (32 females and 28 males) aged between 52
and 74 years with radiologically confirmed stage III–IV coxarthrosis according to the
Kellgren–Lawrence classification were included. Patients were recruited from the
Department of Orthopedics and Rheumatology at [Institution name].
Exclusion criteria were: presence of rheumatoid arthritis, systemic autoimmune diseases,
recent corticosteroid therapy, or acute infections. A control group of 20 age- and sex-
matched healthy individuals without radiological signs of osteoarthritis was also examined.
Clinical assessment: Patients underwent a complete clinical evaluation including pain
intensity measurement using the Visual Analog Scale (VAS), functional assessment with the
Harris Hip Score (HHS), and radiological grading by plain X-ray and MRI.
Sample collection: Peripheral blood samples were obtained from all participants. Synovial
fluid samples were aspirated from 25 patients undergoing preoperative evaluation before hip
replacement surgery. Synovial tissue biopsies were collected during total hip arthroplasty
procedures (n=15).
LABORATORY METHODS:
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1. Cytokine measurement: Levels of IL-1β, IL-6, TNF-α, and IL-10 were quantified in
serum and synovial fluid using enzyme-linked immunosorbent assay (ELISA) kits
(BioLegend, USA).
2. Flow cytometry: Peripheral blood mononuclear cells (PBMCs) were isolated and
analyzed for T cell subsets (CD4+, CD8+, Treg cells) and B lymphocytes (CD19+)
using fluorescent-labeled antibodies (BD Biosciences).
3. Immunohistochemistry: Synovial tissue sections were stained for CD68
(macrophages), CD4 (T cells), and CD20 (B cells) to evaluate immune cell
infiltration.
4. Molecular analysis: Quantitative real-time PCR (qPCR) was performed to measure
gene expression of MMP-3, MMP-9, and ADAMTS-5, as well as cytokine genes in
synovial tissue.
5. Inflammatory markers: Systemic inflammation was assessed by measuring C-
reactive protein (CRP) and erythrocyte sedimentation rate (ESR) using standard
laboratory techniques.
6. Statistical analysis- All data were analyzed using SPSS version 25.0. Continuous
variables were expressed as mean ± standard deviation (SD). Comparisons between
groups were performed using the Student’s t-test or Mann–Whitney U test where
appropriate. Correlations between cytokine levels and clinical parameters (VAS,
HHS) were assessed using Pearson’s correlation coefficient. A p-value <0.05 was
considered statistically significant.
In patients with stage III–IV coxarthrosis, a clear pattern of immunological alterations was
observed compared to the control group. The clinical evaluation confirmed advanced disease,
with patients reporting persistent pain, limited mobility, and reduced hip function.
Radiological findings showed severe joint space narrowing, osteophyte formation, and
subchondral bone changes, consistent with late-stage degeneration. Laboratory analysis
revealed an increase in pro-inflammatory cytokines, particularly IL-1β, TNF-α, and IL-6,
both in serum and synovial fluid. At the same time, the level of anti-inflammatory cytokines,
such as IL-10, was relatively lower, indicating a disturbed balance between pro- and anti-
inflammatory mediators. Flow cytometry demonstrated a shift in immune cell populations.
Patients with advanced coxarthrosis showed an increased proportion of activated T helper
cells and B lymphocytes, while the regulatory T-cell population was reduced. These findings
suggest impaired immune regulation and sustained inflammatory activity. Histological and
immunohistochemical studies of synovial tissue revealed infiltration of macrophages and
lymphocytes, along with expression of inflammatory mediators within the synovial
membrane. These structural changes correlated with clinical symptoms, reflecting the role of
chronic inflammation in the progression of joint destruction. Systemic markers of
inflammation, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR),
were also moderately elevated in most patients, further supporting the presence of ongoing
immune activation beyond the local joint environment. Overall, the results demonstrate that
patients with stage III–IV coxarthrosis exhibit a combination of local joint inflammation and
systemic immune dysregulation, both of which contribute to the severity of the disease. In
patients with stage III–IV coxarthrosis, clinical examination confirmed the presence of
severe pain, joint stiffness, and significant reduction of hip mobility. Most patients reported
persistent pain during both movement and rest, which was consistent with radiological
findings showing marked joint space narrowing, large osteophytes, and subchondral
sclerosis. Immunological analysis revealed clear disturbances in cytokine balance. Pro-
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inflammatory mediators such as IL-6 and TNF-α were found to be elevated, while the anti-
inflammatory cytokine IL-10 was relatively reduced. This imbalance reflects a
predominance of chronic inflammation over protective immune regulation. Flow cytometry
indicated an increased activity of T helper cells and B lymphocytes, whereas the proportion
of regulatory T cells was lower than in healthy individuals. These changes point to impaired
immunological tolerance and persistent activation of the immune system. Histological
examination of synovial tissue samples showed infiltration of immune cells, thickening of
the synovial lining, and expression of inflammatory mediators, confirming that the local
joint environment is highly immunoreactive in advanced disease. Additionally, systemic
inflammatory markers such as CRP and ESR were moderately elevated, indicating that the
immune response in late-stage coxarthrosis is not limited to the joint but also has systemic
features. Overall, the results demonstrate that patients with stage III–IV coxarthrosis are
characterized by a combination of advanced structural degeneration and ongoing immune
dysregulation, both contributing to the severity of clinical symptoms. The present study
highlights that stage III–IV coxarthrosis is not merely a degenerative joint disease but also
involves profound immunological alterations. Traditionally, osteoarthritis was considered a
purely “mechanical wear-and-tear” disorder. However, accumulating evidence now supports
the concept that the immune system plays an equally important role in its progression. Our
findings add to this perspective by demonstrating that advanced coxarthrosis is accompanied
by both local and systemic immune dysregulation. One of the most striking aspects observed
was the imbalance between pro- and anti-inflammatory cytokines. Elevated levels of IL-6
and TNF-α, combined with reduced IL-10, indicate that chronic inflammation persists even
in the late stages of disease. Similar patterns have been reported in previous studies, where
synovial fluid analysis revealed high concentrations of pro-inflammatory mediators driving
cartilage degradation and bone remodeling. This suggests that immune activation is not a
secondary phenomenon but an integral part of the disease mechanism. Another important
finding was the alteration in lymphocyte subpopulations. The predominance of T helper
cells and B lymphocytes, alongside reduced regulatory T cells, points to impaired immune
tolerance. This study demonstrates that stage III–IV coxarthrosis is not a simple
consequence of mechanical wear, but rather the result of a complex interplay between
structural degeneration and immune dysregulation. The observed imbalance of cytokines,
the activation of T and B lymphocytes, and the persistent inflammatory state of synovial
tissue all point to the essential role of the immune system in disease progression. While
radiological changes explain the severity of pain and joint dysfunction, it is the underlying
immunological activity that sustains chronic inflammation and accelerates tissue destruction.
Therefore, advanced coxarthrosis should be viewed as both a degenerative and
immunoinflammatory condition. From a clinical perspective, these findings highlight the
need for a more comprehensive approach to treatment. Alongside conventional orthopedic
interventions, strategies aimed at modulating immune responses may offer new
opportunities to slow progression, reduce symptoms, and improve patients’ quality of life.
Ultimately, understanding the immunological aspects of late-stage coxarthrosis opens the
door to innovative therapies that go beyond joint replacement and address the root causes of
inflammation and degeneration.
REFERENCES:
1. Goldring, M. B., & Otero, M. (2011). Inflammation in osteoarthritis. Current Opinion in
Rheumatology, 23(5), 471–478.
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lu
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gu
st
,2
02
5
,
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ED
IC
AL
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IE
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PA
CT
FA
CT
OR
:7
,8
9
2. Berenbaum, F. (2013). Osteoarthritis as an inflammatory disease (osteoarthritis is not
osteoarthrosis!).
Osteoarthritis
and
Cartilage,
21(1),
16–21.
https://doi.org/10.1016/j.joca.2012.11.012
3. Scanzello, C. R., & Goldring, S. R. (2012). The role of synovitis in osteoarthritis
pathogenesis. Bone, 51(2), 249–257.
https://doi.org/10.1016/j.bone.2012.02.012
4. Wojdasiewicz, P., Poniatowski, Ł. A., & Szukiewicz, D. (2014). The role of inflammatory
and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators of
Inflammation, 2014, 1–19.
https://doi.org/10.1155/2014/561459
5. Robinson, W. H., Lepus, C. M., Wang, Q., Raghu, H., Mao, R., Lindstrom, T. M., &
Sokolove, J. (2016). Low-grade inflammation as a key mediator of the pathogenesis of
osteoarthritis.
Nature
Reviews
Rheumatology,
12(10),
580–592.
https://doi.org/10.1038/nrrheum.2016.136
6. Benito, M. J., Veale, D. J., FitzGerald, O., van den Berg, W. B., & Bresnihan, B. (2005).
Synovial tissue inflammation in early and late osteoarthritis. Annals of the Rheumatic
Diseases, 64(9), 1263–1267.
https://doi.org/10.1136/ard.2004.025270
7. Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J. P., & Fahmi, H. (2011). Role
of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews
Rheumatology, 7(1), 33–42.
