-
International Immunopharmacology Jun 2024Th17 and Treg play important roles in AS, but their single and dual TCR pairing types, ratios, and CDR3 characteristics remain unknown.
OBJECTIVE
Th17 and Treg play important roles in AS, but their single and dual TCR pairing types, ratios, and CDR3 characteristics remain unknown.
METHODS
Single-cell RNA + TCR-seq results from six AS patients were used to cluster T-cell subpopulations and analyze the single and dual TCR T cell ratio, diversity/clonality/overlap of CDR3, and expression of transcription factors.
RESULTS
1. AS patients have about 10% of dual TCR T cells, and SFMC have decreased diversity CDR3 libraries and significant clonal proliferation compared to PBMC. 2. Dual TCR ratio: memory T > naive T; pTh 17 > Th17; Treg /Th17/Th1/EM significantly higher than naive CD4 + T/CM, Pathogenic Th17 cells contain clonally proliferating single TCR and dual TCR cells. 3. The expression of single TCR and dual TCR transcription factors of each T cell subpopulation was basically the same, but there was differential expression of characteristic transcription factors, e.g. Foxp3, CTLA4, STAT5B, IL10RB, LAG3 in dual TCR Treg was higher than that of single TCR Treg; TNFSF10/12, TNFRSF4/14, CCL5, KLRB1 in dual TCR pTh17 were significantly higher than those in single TCR pTh17. 4. Between naive CD4 + T, pTh17, Th1 and Treg, there are partially identity identical tcr paired cells.
CONCLUSIONS
The high proportion of dual TCR T cells such as pTh17 and Treg in AS and the high expression of some transcription factors suggested a close association with self-response in AS; The overlap of CDR3 between Th1, Th17,pTh17, and Treg in AS suggested that the subpopulations may be differentiated from each other to regulate the inflammatory homeostasis and progression.
Topics: Humans; T-Lymphocytes, Regulatory; Th17 Cells; Receptors, Antigen, T-Cell; Male; Spondylitis, Ankylosing; Adult; Female; Single-Cell Analysis; Autoimmunity; RNA-Seq; Transcription Factors; Young Adult; Middle Aged
PubMed: 38796963
DOI: 10.1016/j.intimp.2024.112279 -
Modern Rheumatology May 2024This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS).
OBJECTIVES
This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS).
METHODS
We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group.
RESULTS
At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis.
CONCLUSIONS
CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.
PubMed: 38795054
DOI: 10.1093/mr/roae048 -
Arthritis Research & Therapy May 2024Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS.
METHODS
This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16-48.
OUTCOMES
nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1-6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points.
RESULTS
269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4-8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8-24 (12-40) weeks with tofacitinib vs. 24-32 weeks (32 weeks-not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment.
CONCLUSIONS
Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03502616, 11 April 2018.
Topics: Humans; Piperidines; Spondylitis, Ankylosing; Pyrimidines; Female; Male; Adult; Pyrroles; Middle Aged; Treatment Outcome; Fatigue; Double-Blind Method; Pain; Time Factors; Protein Kinase Inhibitors
PubMed: 38790040
DOI: 10.1186/s13075-024-03313-w -
Terapevticheskii Arkhiv Dec 2023To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
AIM
To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
MATERIALS AND METHODS
The retrospective analysis included 23 patients (13 males; 56.5%) aged 23 to 73 years (median 42, interquartile range 28 to 52 years) with AS (=12) or PsA (=11) who received netakimab therapy from February 2021 to April 2023. Disease activity was assessed every 3-6 months based on the C-reactive protein (CRP) level for all patients according to the BASDAI and ASDAS-CRP indices for AS, DAPSA and PASI for PsA. These indicators were analyzed before therapy and at the last visit to assess the effectiveness of treatment. The results are presented as median (interquartile range).
RESULTS
In all patients treated with netakimab (median duration of treatment 11 months), the CRP level decreased from 10.6 (3.1; 17.3) to 3.1 (1.9; 8.9) mg/L (absolute difference -7.5 mg/L, median relative reduction -60%; =0.008), and the proportion of patients with elevated CRP decreased from 70 to 41%; =0.039. In patients with AS (median duration of treatment 9 months), BASDAI score decreased from 5.8 (4.7; 6.5) to 3.0 (1.9; 3.8) points (absolute difference -2.8 points, median relative reduction of -45%; =0.008) and ASDAS-CRP score decreased from 2.8 (1.9; 3.9) to 1.9 (1.7; 2.6) points (absolute difference -0.9 points, median relative reduction -21%; =0.007). The proportion of patients with high AS activity (BASDAI≥4) decreased from 90% to 20% (=0.031); however, there was no significant change in the CRP level (absolute difference -4.9 mg/L, median relative reduction -57%; =0.110). In patients with PsA (median duration of treatment 18 months), the CRP level decreased from 12.0 (4.5; 17.3) to 3.3 (2.0; 7.8) mg/L (absolute difference -8.7 mg/L, median relative reduction -80%; =0.041), the DAPSA score decreased from 23.0 (19.0; 30.5) to 6.3 (5.2; 13.5) points (absolute difference -16.7 points, median relative reduction -69%; =0.018). Three (13%) patients reported mild to moderate adverse events.
CONCLUSION
The obtained data confirm the effectiveness and safety of netakimab in treating AS and PsA in real-world practice.
Topics: Humans; Male; Female; Middle Aged; Adult; Retrospective Studies; Spondylitis, Ankylosing; Arthritis, Psoriatic; C-Reactive Protein; Antibodies, Monoclonal, Humanized; Treatment Outcome; Aged
PubMed: 38785057
DOI: 10.26442/00403660.2023.12.202547 -
Journal of Orthopaedic Case Reports May 2024Ankylosing spinal disorders present significant challenges in cases of trauma, and the treatment of ankylosed spine infections may also be challenging. However, to the...
INTRODUCTION
Ankylosing spinal disorders present significant challenges in cases of trauma, and the treatment of ankylosed spine infections may also be challenging. However, to the best of our knowledge, only one study to date has addressed this topic, reporting a mortality rate of 62%.
CASE REPORT
Our patients were four men and one woman with a mean age of 72 years. Treatments consisted of intravenous antibiotics, a hard brace, and surgical interventions including percutaneous pedicle screw fixation in two patients, laminectomy and evacuation of the epidural abscess in one, and percutaneous lavage of the affected disc in two. The time from referral to intervention averaged 16 days. The mortality rate was 0% with healing of the infection with segmental bony fusion in four patients.
CONCLUSION
This is the second reported case series of ankylosed spine infections. Early surgical intervention aimed at drainage or stabilization of the infectious lesions is crucial to disease control.
PubMed: 38784890
DOI: 10.13107/jocr.2024.v14.i05.4436 -
Journal of Orthopaedic Case Reports May 2024Coalition is an abnormal, usually congenital, or developmental connection in between or the complete fusion of two bones that are otherwise separate. It is of three...
INTRODUCTION
Coalition is an abnormal, usually congenital, or developmental connection in between or the complete fusion of two bones that are otherwise separate. It is of three types, i.e., synostosis (bony connection), synchondrosis (cartilaginous connection), or syndesmosis (fibrous tissue). Its typical cause is the failure of mesenchymal segmentation and differentiation. Usually, it is seen in tarsal or carpal bones and very rarely in between other bones. Only a single case of a tibiotalar coalition has been reported previously in literature. Herein, we are reporting a case of the talocrural coalition, which is the first one from the Indian sub-continent.
CASE REPORT
A 16-year-old moderately built female patient of Indian origin presented with chronic pain of 1-year duration in the right foot and ankle region on weight bearing. The pain was dull aching type, mild-to-moderate in severity and worsened with activity or prolonged walking, and relieved on taking non-steroidal anti-inflammatory drugs. No relevant history was present. On local examination, diffuse tenderness was present in the ankle and the tarsal bones. Almost negligible dorsiflexion and about 15° plantar flexion of the foot were possible. An initial radiograph of the right ankle revealed osseous fusion between the distal tibia and fibula, as well as between the tibia, fibula, and the dome of the talus. Magnetic resonance imaging (MRI) revealed osseous fusion involving the distal tibia, fibula, and the dome of the talus (both medially and laterally), indicative of talocrural fusion. No edema or inflammation was appreciable in the adjacent tendons or synovium. The patient was explained regarding the pathology and the prognosis. She was managed conservatively and was satisfied.
CONCLUSION
Radiographs play a crucial role in evaluating patients suspected of having a coalition or ankylosis. Complementary tools such as computed tomography and MRI are valuable for a more in-depth assessment of the fusion and aid in surgical planning.
PubMed: 38784884
DOI: 10.13107/jocr.2024.v14.i05.4424 -
JPMA. the Journal of the Pakistan... May 2024To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis... (Comparative Study)
Comparative Study
OBJECTIVES
To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis and ankylosing spondylitis.
METHODS
The comparative, cross-sectional study was conducted from February 2 to December 30, 2022, at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi. The sample comprised healthy controls in group 1, patients of rheumatoid arthritis in group 2 and patients of ankylosing spondylitis in group 3. Blood samples were assessed for levels of superoxide dismutase, malondialdehyde, erythrocyte sedimentation rate and C-reactive protein. Data was analysed using SPSS 25.
RESULTS
Of the 180 subjects, 60(33.3%) were in group 1; 32(53.3%) females and 28(46.7%) males with mean age 34.9±6.4 years. There were 60(33.3%) patients in group 2; 35(58.3%) females and 25(41.7%) males with mean age 46.0±11.1 years. There were 60(33.3%) patients in group 3, and all 60(100%) were males with mean age 35.9±6.9 years. Superoxide dismutase level was significantly low and malondialdehyde level was significantly high in groups 2 and 3 compared to group 1 (p<0.05). Erythrocyte sedimentation rate was the highest in group 2, followed by group 3 (p<0.05). C-reactive protein levels were the highest in group 2 and the lowest in group 3 (p<0.05). A significantly negative correlation (p<0.001) was found between superoxide dismutase and malondialdehyde.
CONCLUSIONS
Oxidative stress played a pivotal role in chronic inflammatory rheumatic diseases, like rheumatoid arthritis and ankylosing spondylitis.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Arthritis, Rheumatoid; Oxidative Stress; Malondialdehyde; Superoxide Dismutase; Blood Sedimentation; Adult; Cross-Sectional Studies; C-Reactive Protein; Lipid Peroxidation; Middle Aged; Biomarkers; Case-Control Studies; Pakistan
PubMed: 38783435
DOI: 10.47391/JPMA.9286 -
Advances in Rheumatology (London,... May 2024The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis... (Comparative Study)
Comparative Study
BACKGROUND
The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA.
METHODS
An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele's presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant.
RESULTS
Of the participants, 90.3% (n = 56) were HLA-B27 positive according to FC, while 79% (n = 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived.
CONCLUSIONS
FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.
Topics: Humans; HLA-B27 Antigen; Cross-Sectional Studies; Male; Female; Polymerase Chain Reaction; Adult; Flow Cytometry; Axial Spondyloarthritis; Brazil; Middle Aged; Sensitivity and Specificity; Spondylitis, Ankylosing
PubMed: 38783377
DOI: 10.1186/s42358-024-00383-x -
The Journal of Craniofacial Surgery May 2024The treatment of temporomandibular joint (TMJ) ankylosis in children is a great challenge for surgeons. Costochondral graft (CCG) is a common method of reconstructing...
The treatment of temporomandibular joint (TMJ) ankylosis in children is a great challenge for surgeons. Costochondral graft (CCG) is a common method of reconstructing the TMJ in children. However, the growth pattern of CCG is unpredictable. In this study, we introduced a surgical-orthodontic approach and evaluated the growth results of the mandible and maxilla in children with TMJ ankylosis through 3-dimensional computed tomography measurements. A prospective cohort study was conducted on child patients diagnosed as having TMJ ankylosis between September 1, 2018 and June 1, 2020. Computer-aided virtual mandibular position guided the CCG, and removable functional appliance was used after surgery. The maximal incisal opening (MIO), the maxilla height, and the length of mandibular ramus were determined. Paired t test was performed to analyze the differences among various stages. Six patients (3 females, 3 males; aged 6-9 y) were included in this study. MIO was 12.4 mm before surgery and improved to 36.8 mm after 42.8 months' follow-up. Mandible length increased by 5.1 mm in the affected side and by 5.3 mm in the unaffected side, without significant difference. The affected maxilla height increased by 6.7 mm, which was more than 5.0 mm in the unaffected side. In conclusion, continued growth of mandible and maxilla can be achieved through CCG combined with functional appliance treatment for children TMJ ankylosis.
PubMed: 38771188
DOI: 10.1097/SCS.0000000000010194