HLA-B27 Research Articles

A systematic study on the elevated risk of ankylosing spondylitis in adolescents engaged in intense physical exercise

This study investigates the link between intense physical activity during adolescence and the onset of ankylosing spondylitis (AS), particularly in individuals having the human leukocyte antigen (HLA)-B27 antigen, a known genetic marker for AS. The systematic literature review included studies published between 2014 and 2024. . Keywords and search terms included combinations of "ankylosing spondylitis," "HLA-B27," "adolescence," "intense physical exercise," and "genetic predisposition. Inclusion criteria focused on studies involving adolescents aged 15-24 years with genetic predispositions such as HLA-B27. Exclusion criteria included studies with unrelated outcomes such as individuals not within the target adolescent age range, non-peer-reviewed articles, and those with insufficient data on the target population. Findings revealed that adolescents with the HLA-B27 antigen who engaged in heavy weight exercise were at a heightened threat of developing AS. The mechanical stress from intense physical activity potentially triggered or exacerbated inflammation at entheses in genetically predisposed individuals. However, the onset of AS was not universally observed in all HLA-B27 positive individuals who participated in strenuous exercise, suggesting other genetic and environmental factors’ involvement. The study suggests that strenuous exercise during adolescence may act as a significant contributing factor to the onset of AS in individuals having a genetic predisposition such as HLA-B27. While not all individuals having HLA-B27 develop AS, genetic and environmental factors’ combination, including intense physical activity, may accelerate disease progression.

Familial mediterranean fever in a patient with ankylosing spondylitis: could familial mediterranean fever explain a typical eight-year ankylosing spondylitis?

Patients with familial mediterranean fever (FMF) often present with musculoskeletal involvement typical of spondyloarthropathy (SpA) or ankylosing spondylitis (AS), posing a diagnostic challenge for medical practitioners and leading to the description of the FMF-related SpA/AS clinical spectrum. Currently, the available data focuses on SpA diagnosis in patients with known FMF, while the contrary is rarely reported in the medical literature. We describe an unusual case of concomitant FMF diagnosis in a patient with an eight-year long history of typical, human leukocyte antigen-B27 positive AS on adalimumab treatment, who presented with recurrent febrile attacks and abdominal pain. The laboratory work-up revealed high titres of serum amyloid A while genetic testing was positive for the pathogenic M694V heterozygous variant in the MEFV gene. The patient was promptly treated with colchicine, showing complete remission of clinical symptoms and normalisation of inflammatory markers to date. We also performed a review of the available literature elaborating on the interrelationship of AS and FMF in terms of pathogenesis and clinical characteristics. Our case highlights the need for reporting of similar cases and further explores the association of AS and FMF as distinct clinical entities or as constituents of the same disease continuum model.

HLA-B27 Frequency and its Association with Ankylosing Spondylitis in Indian Population: A Multi-City Analysis from a Single-Center Study

The human leukocyte antigen HLA-B*27 is a Class 1 antigen of the major histocompatibility complex (MHC) with B locus and has been established in association with pathogenesis of Ankylosing Spondylitis (AS) since 1973. AS is a multifactorial disease which occurs due to interaction between genes, environment, mechanical stress, microbiota and infection. The ankylosing spondylitis is characterized by inflammation of spine, backpain, stiffness of lower back and hips, extrarticular organs such as eyes, and cardiovascular system. In severe cases this may cause the fusion of vertebrae. The current study highlights the mechanism involved in the pathogenesis of AS with a focus to investigate the frequency of HLA B*27 in suspected cases of AS. The patients were recruited from rheumatology clinics of India from age group of 13-69 years. Patients with suspected cases of AS who met the clinical criteria for AS were tested for HLA-B*27. One thousands and four patients were tested for HLA B*27 using RTPCR method. Out of 1004 subjects, 124 (12.35%) were positive for HLA-B*27. Among these, Male/Female ratio was 2.7. Majority of subjects were from North India. The current study highlights the HLA B27 positivity in association with pathogenesis of AS and indicates that HLA B27 serves as a rapid prognostic and diagnostic genetic marker for detection of AS.

Analysis of ANO6, HAPLN1, and EDIL3 Polymorphisms in Patients with Ankylosing Spondylitis in a Chinese Han Population: A Case-Control Study.

Background: Earlier research has demonstrated a genetic basis for the susceptibility to ankylosing spondylitis (AS) and the severity of AS. By employing a genome-wide association study, recent work has established a correlation between the susceptibility to AS and the ANO6, HAPLN, and EDIL3 genes in a Western study population-though alternative studies have not corroborated these findings. This study aims to examine the effects of ANO6, HAPLN1, and EDIL3 polymorphisms on the susceptibility and severity of AS among the predominantly Chinese Han population. Methods: The study involved the collection of blood samples from 497 patients with AS and 498 nonrelated healthy individuals. All participants in the study were human leukocyte antigen (HLA) HLA-B27 positive and of Han Chinese descent. Illness severity was the criteria used for classifying patients with AS. Thirteen tagSNPs in ANO6, HAPLN1, and EDIL3 were chosen and then subjected to genetic typing. Analysis was conducted on the occurrence rates of various genotypes and alleles between the control group and patients with varying AS severity. Results: Following Bonferroni correction, it was found that the rs4768085 and rs17095830 single nucleotide polymorphism (SNPs) in ANO6 were related to the susceptibility to AS. Further, the rs6869296 SNP in HAPLN1 and the rs2301071 SNP between EDIL3 and HAPLN1 were also related to AS susceptibility. Regarding AS severity, the rs4768085, rs2897868, rs7965430, and rs11182965 SNPs in ANO6 were found to be associated. Conclusions: Among the Han population in China, the ANO6 and HAPLN1 genes are related to the susceptibility to AS; the ANO6 gene is also associated with the severity of AS.

SYSTEMIC IMMUNE INFLAMMATION INDEX AND PAN-IMMUNE INFLAMMATION VALUE IN PREDICTING HUMAN LEUKOCYTE ANTIGEN-B27 POSITIVITY: A STUDY ON ANKYLOSING SPONDYLITIS PATIENTS

Objective: Ankylosing spondylitis (AS) is defined as both an auto-immune and autoinflammatory illness. Human leukocyte antigen B27 (HLA-B27), which is extensively employed in the diagnosis of chronic inflammatory diseases, is the basic laboratory parameter of axial spondylarthritis including AS. Systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV), obtained by formulating complete blood count parameters, are promising biomarkers that reflect systemic inflammation and local immune response and predict prognosis in diseases. The aim of this study was to investigate the sensitivity and specificity of SII and PIV biomarkers in predicting HLA-B27 positivity in AS patients. Materials and Methods: The research included 68 individuals with HLA-B27 tests (+) (AS group) and 102 patients with HLA-B27 tests (-) (control group). Results: In the AS group, lymphocyte and mean platelet volume values were determined to be lower than in the control group, while other complete blood count parameters, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were found to be higher. While the SII and PIV values of the AS group determined a positive relation with CRP and ESR levels, they did not show a correlation in the control group. While the sensitivity for PIV in predicting HLA-B27 positivity was found to be 83.80% and the specificity was found to be 84.30%, for SII the sensitivity was found to be 83.80% and the specificity was found to be 86.30%. Conclusion: Easily and rapidly accessible biomarkers SII and PIV can potentially be used to predict HLA-B27 positivity in AS patients.

Prevalence of Human Leukocyte Antigen Alleles Polymorphism in North Indian Population

Background Human leukocyte antigens (HLA) are highly polymorphic glycoproteins required for immune response and recognizing self or non-self. Knowing the HLA diversity in a population may be helpful in the selection of organ allocation for transplantation. We aimed to retrospectively analyze the prevalence of HLA, A, B, C, DRB1, and DQA1 alleles frequency in the north Indian population. Materials and Methods HLA antigen allele data were retrospectively analyzed from a transplant cohort of 2259 subjects. HLA-A, B, and DRB1 frequency were determined in 2259, HLA-C in 759 and DQA1 in 751 subjects. Results The most abundant HLA-A antigen alleles were HLA-A*01(25.41%), HLA-A*02 (24.83%), HLA-A*11 (17.53%), HLA-A*24 (10.27%), HLA-A*03 (9.07%). HLA-B antigen alleles were HLA-B*35 (20.54%), HLA-B*15 (15.36%), HLA-B*40 (13.59%), HLA-B*07 (10.14%), HLA-B*44 (7.79). HLA-C antigen alleles were HLA-C*07 (28.06%), HLA-C*04 (20.42%), HLA-C*03 (15.55%), HLA-C*06 (13.04%), HLA-C*12 (5.27%). HLA-DRB1 alleles were HLA-DRB1*07 (21.60%), HLA-DRB1*04 (19.74%), HLA-DRB1*10 (13.15%), HLA-DRB1*03 (10.80%), HLA-DRB1*11 (8.63%). HLA-DQA1 antigen alleles were HLA-DQA1*03 (35.42%), HLA-DQA1*02 (30.89%), HLA-DQA1*05 (21.84%), HLA-DQA1* 06 (10.12%), HLA-DQA1*04 (1.07%). Conclusion The most frequent HLA alleles were HLA-A*01(25.41%), HLA-B*35 (20.54%), HLA-C*07 (28.06%), HLA-DRB1*07(21.60%), HLA-DQA1*03(35.42%) in north Indian population.

Beyond the spine: a case of ankylosing spondylitis complicated by secondary amyloidosis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory condition primarily affecting the spine and sacroiliac joints, often associated with human leukocyte antigen B27 (HLA-B27) positivity. While musculoskeletal symptoms are typical manifestations, AS can also lead to systemic complications, including secondary systemic amyloidosis (SSA), also known as Amyloid A (AA) amyloidosis, involving multiple organs.Case presentationWe present a case of a 45-year-old Asian male with a complex medical history, including diabetes and hypertension, who developed AS complicated by SSA. The patient exhibited a diverse range of symptoms, including cardiac, renal, gastrointestinal, and musculoskeletal manifestations. He reported shortness of breath on exertion, orthopnea, pedal edema, generalized weakness, back pain, neck pain, low-grade fever, decreased appetite, frothy urine, and significant weight loss over the past year. Diagnostic evaluations revealed HLA-B27 positivity and histologically confirmed AA amyloidosis, providing a comprehensive understanding of the systemic involvement.ConclusionThis case report highlights the intricate interplay between AS and SSA, particularly AA amyloidosis, with a focus on its systemic impact beyond musculoskeletal symptoms. The tragic outcome, marked by severe cardiac involvement, underscores the challenges in managing such complex cases. This report emphasizes the importance of early diagnosis and treatment of AS to prevent severe complications, along with vigilant monitoring and individualized treatment plans, as well as the need for further research to enhance our understanding and improve management strategies for AS-related amyloidosis.

Frequency of HLA-B27 Haplotype Among Patients with Acute Anterior Uveitis and Controls in Ethiopia

ABSTRACT Purpose We compared the distribution of the HLA-B27 allele among Ethiopian patients with acute anterior uveitis (AAU) and controls without that disease. Methods The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed for 64 patients, with AAU using the real-time polymerase chain reaction (RT-PCR), and the results were compared to those from a panel of 192 healthy, unrelated volunteer control participants (refraction patients and volunteers) free of signs of anterior uveitis. Other outcomes were assessed comparing HLA-B27 positive vs. negative patients. Results The histocompatibility antigen HLA-B27 was identified in 6 out of 64 (9.4%) AAU patients, compared with 1.0% in controls (Odds Ratio = 9.8, 95% CI (1.93, 50.01)). Sub-group analysis of the cases revealed that patients with HLA-B27 positivity had a higher incidence of ocular hypertension (Odds Ratio = 5.93, 95% CI (1.29, 27.2)). Conclusion The antigen HLA-B27 was represented ~10-fold more frequently in the patient group than in the control group. HLA-B27 allele distribution in both cases and controls is lower than in reports from Caucasian and Asian populations, but similar to South Africa.

The Impact of Different MEFV Genotypes on Clinical Phenotype of Patients with Familial Mediterranean Fever: Special Emphasis on Joint Involvement

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this retrospective cohort study, we aimed to assess the effects of various MEFV genotypes on the clinical characteristics of the patients, with a special focus on the joint involvement. In total, 782 patients with FMF were categorized into 3 groups according to the MEFV mutation; Group 1: Patients homozygous for M694V; Group 2: Patients carrying other pathogenic MEFV variants in exon 10 in homozygous or compound heterozygous states; and Group 3: FMF patients with other variants or without mutations. Clinical and demographic findings were compared between groups. Among the 782 FMF patients, total frequency of arthritis was 237 (30.3%): 207 (26.4%) were acute monoarthritis and 67 (8.5%) were chronic arthritis. Both the frequency of arthritis (acute and/or chronic) (40.4% vs. 24.8% vs. 26.7%; p:0.001) and acute monoarthritis (35.4% vs. 20% vs. 23.7%; p:0.001) were significantly higher in Group 1 than in the other groups. FMF patients with chronic arthritis showed a distinct juvenile idiopathic arthritis (JIA) distribution pattern with a more frequent enthesitis-related arthritis (ERA) subtype (43.2%). HLA-B27 was positive in 24% of the ERA patients.Conclusion: Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis comparing to other MEFV genotypes. In addition, the risk of chronic arthritis seems not related to the MEFV mutations. However, FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA and undifferentiated arthritis subtype.What is known:• Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritisWhat is new:• FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA subtype• ERA patients with negative HLA-B27 antigen should also be assessed for polyserositis episodes of FMF, especially in countries with high FMF carrier frequency

Features of Axial Spondyloarthritis in Two Multicenter Cohorts of Patients with Psoriasis, Uveitis, and Colitis Presenting with Undiagnosed Back Pain.

We aimed to assess: 1. The frequency of axial spondyloarthritis (axSpA) according to extra-articular presentation and HLA-B27 status; 2. Clinical and imaging features that distinguish axSpA from non-axSpA; 3. The impact of MRI on diagnosis and classification of axSpA. The Screening in Axial Spondyloarthritis in Psoriasis, Iritis, Colitis, (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with PsO, AAU, or IBD, were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation. The primary outcome was proportion of patients diagnosed with axSpA by final global evaluation. Frequency of axSpA was 46.7%, 61.6%, and 46.8% in SASPIC-1 cases (n=212) and 23.5%, 57.9%, and 23.3% in SASPIC-2 cases (n=151) with PsO, AAU, or IBD, respectively. Among B27 positives, axSpA was diagnosed in 70%, 74.5%, and 66.7% in SASPIC-1, and in 71.4%, 87.8%, and 55.6% in SASPIC-2 in patients with PsO, AAU, or IBD, respectively. All musculoskeletal clinical features were non-discriminatory. MRI was indicative of axSpA in 60-80% of patients and MRI in all patients (SASPIC-2) versus on-demand (SASPIC-1) led to 25% fewer diagnoses of axSpA in HLA B27 negatives with PsO or IBD. Performance of the ASAS classification criteria was greater with routine MRI (SASPIC-2) though sensitivity was lower than previously reported. Optimal management of patients presenting with PsO, AAU, IBD, and undiagnosed chronic back pain should include referral to a rheumatologist. Conducting MRI in all patients enhances diagnostic accuracy.

Characterisation of delayed severity flares in patients with HLA-B27-associated anterior uveitis

Background/aimsTo explore and characterise the clinical phenotype of acute anterior uveitis flares with delayed severity in patients with human leucocyte antigen B27 (HLA-B27)-associated anterior uveitis.MethodsRetrospective chart review of patients with...

Regional Differences in Diagnosis Journey and Healthcare Utilization: Results from the International Map of Axial Spondyloarthritis (IMAS).

To assess differences in thediagnosis journey and access to care in a large sample of patients with axial spondyloarthritis (axSpA)from around the world,included in the International Map of Axial Spondyloarthritis (IMAS). IMAS was a cross-sectional online survey (2017-2022) of 5557 unselected patients with axSpA from 27 countries. Across five worldwide geographic regions, the patient journey until diagnosis and healthcare utilization in the last 12 months prior to survey were evaluated. Univariable and multivariable linear regression was used to analyze factors associated with higher healthcare utilization. Of 5557 participants in IMAS, the diagnosis took an average of 7.4 years, requiring more than two visits to HCPs (77.7% general practitioner and 51.3% rheumatologist), and more than two diagnostic tests [67.5% performed human leukocyte antigen B27 (HLA-B27), 64.2% x-ray, and 59.1% magnetic resonance imaging (MRI) scans]. North America and Europe were the regions with the highest number of healthcare professional (HCP) visits for diagnosis, while the lowest number of visits was in the Asian region. In the previous 12 months, 94.9% (n=5272) used at least one healthcare resource, with an average of 29 uses per year. The regions with the highest healthcare utilization were Latin America, Europe, and North America. In the multiple linear regression, factors associated with higher number of healthcare utilization were younger age (b=-0.311), femalegender (b=7.736), higher disease activity (b=1.461), poorer mental health (b=0.624), greater functional limitation (b=0.300), greater spinal stiffness (b=1.527), and longer diagnostic delay (b=0.104). The diagnosis of axSpA usually takes more than two visits to HCPs and at least 7 years. After diagnosis, axSpA is associated with frequent healthcare resource use. Younger age, female gender, higher disease activity, poorer mental health, greater functional limitation, greater spinal stiffness, and longer diagnostic delay are associated with higher healthcare utilization. Europe and North America use more HCP visits and diagnostic tests before and after diagnosis than the other regions.

Utility of common investigations for suspected inflammatory arthritis in adults.

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient's history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad 'rheumatological panel' increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor.

FAILURE OF THE FIRST BIOLOGIC TREATMENT IN PATIENTS WITH SPONDYLOARTHRITIS: DATA FROM THE MOROCCAN REGISTRY OF BIOLOGICAL THERAPIES IN RHEUMATIC DISEASES (RBSMR)

Introduction:Spondyloarthritis is a group of chronic inflammatory rheumatic diseases that commonly affect young adults. The advent of biological background treatments has revolutionized the management of these conditions, although some patients may not respond adequately to these interventions. Objectives: To assess the prevalence of first biological treatment failure in spondyloarthritis and identify the factors associated with this outcome. Methods: Our study included patients with spondyloarthritis retained according to the ASAS criteria, aged over 18 years, treated with biological treatment, and providing written informed consent. The participants were sourced from the ten rheumatology departments in Morocco, utilizing data from the RBSMR registry, a multicenter historical-prospective registry. Primary failure was characterized by treatment inefficacy within the initial six months, while secondary failure concerns cases of ineffectivenessbeyond six months of treatment. Patients were assessed every six months with a scheduled follow-up period of three years. Inclusion began in June 2017 and ended in January 2019, when the database was first frozen. Results: A total of 194 patients were included in the study. The mean age was 40.23 years with a standard deviation of 13.68. The gender ratio was 1.73 (M/F). The average disease duration was 615.9 weeks with a standard deviation of 349.12. HLA-B27 antigen was positive in 66% of patients. Peripheral involvement was observed in 70% of patients, axial involvement in 96.4%, and enthesic involvement in 61.5%. Radiographic sacroiliitis was identified in 87.6% of patients, radiographic coxitis in 40.7%, and sonographic coxitis in 19.8%. Regarding extra-articular manifestations, 14.5% of patients experienced anterior uveitis, 6.9% had cutaneous psoriasis, and 10.7% had concomitant chronic inflammatory bowel disease. The ASDAS CRP indicated high activity in 50.9% of patients, and the BASDAI (spondyloarthritis activity index) exceeded 4 in 79.2% of patients. During the initial visit, 22.5% of patients were undergoing corticosteroid therapy, and 53.8% were receiving csDMARDs. Etanercept was the most commonly prescribed biological, accounting for 33%. Over the three-year follow-up, five primary failures and 17 secondary failures to the first biological treatment were observed (eight failures at the 12th month, six at the 18th month, and three at the 24th month), resulting in a prevalence of 11,85% for the failure of the first biological. In bivariate analysis, no statistically significant factors were found to be associated with the failure of the first biological at the 6th, 12th, or 24th month visits. However, at the 18th-month visit, both the average BASDAI and C-reactive protein (CRP) levels were statistically higher in patients who experienced failure with the first biological. Conclusion: The failure of the first biologicaltreatment is a rather rare situation in our study. Specific factors were notably linked to this failure and should be considered in patient management, particularly elevated BASDAI and CRP values. These factors have also been reported in the literature to be associated with first biological treatment failure, along with additional factors.

Human leukocyte antigen HLA-B*57:01 status in HIV-1 patients developing hypersensitivity reactions in Benin: a pilot study

BackgroundAntiretroviral drugs in people living with HIV-1 (PLHIV-1) often trigger side effects which may lead to discontinuation or failure of treatment. Human Leukocyte Antigen B*57:01 (HLA-B*57:01) allele is known to predict hypersensitivity reactions to Abacavir. Very few data are available on the prevalence of HLA-B*57:01 allele in PLHIV-1 in African countries. This study aimed to screen for HLA-B*57:01 allele in PLHIV-1 in Benin.MethodsThis pilot study was carried out on one hundred ten PLHIV-1 enrolled in two health facilities in Benin. Socio-demographic and clinical data were collected. Biological data were determined and HLA-B*57:01 allele was genotyped, using Single Specific Primer-Polymerase Chain Reaction in blood samples.Results70% of participants were female. PLHIV-1 were under TDF + 3TC + DTG (47.2%) or TDF + 3TC + EFV (57.3%). Their median age was 41 [36-48.75] years and the average CD4 + T cell count was 249 [130-381.25] cells/µl. The average viral load in treatment failure PLHIV-1 was 4.7 [3.9–5.2] Log10. At the inclusion date, twenty-nine (26.4%) PLHIV-1 under TDF + 3TC + EFV have developed hypersensitivity reactions. None of 110 patients had shown HLA-B*5701 allele.ConclusionOur study revealed that HLA-B*57:01 allele was very rare in PLHIV-1 in Benin, suggesting that its screening before starting the Abacavir regimen did not seem necessary.

Chronic recurrent multifocal osteomyelitis: Case report and review of the literature.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.

Retention Rate of Ixekizumab in Psoriatic Arthritis: A Real-World Study.

We aimed to examine the drug retention rate (DRR) of the interleukin-17 inhibitor ixekizumab in a real-world monocentric cohort of psoriatic arthritis (PsA) patients and to assess the predictors of drug discontinuation. Consecutive PsA patients who underwent treatment with ixekizumab from October 2019 to February 2023 were enrolled in this observational, retrospective, monocentric study. Clinical records were assessed at baseline and throughout the follow-up period. We collected sociodemographic data, smoking habits, body mass index, the presence of Human Leukocyte Antigen B27, comorbidities, disease involvement and duration, previous therapy, discontinuation of ixekizumab, reasons for discontinuation, and adverse events (AEs). DRR was evaluated as time to drug discontinuation and assessed through Kaplan-Meier curves. Baseline factors predicting drug discontinuation were investigated through logistic regression models. Eighty PsA patients were included in this study. Ixekizumab was administered at a dose of 160 mg by subcutaneous injection at baseline, followed by 80 mg every four weeks thereafter. Ixekizumab had a 38-month-cumulative DRR of 43.8%, accounting for both inefficacy and AEs. When considering only inefficacy, the DRR was 62.6%. Comorbidities (p = 0.665), obesity (p = 0.665), smoking (p = 0.884), disease duration ≤ 2 years (p = 0.071), axial (p = 0.131) and skin involvement (p = 0.460), and previous therapies, including conventional synthetic (p = 0.504) and biological (p = 0.474) Disease-Modifying Antirheumatic Drugs (bDMARDs), as well as the number of previous bDMARDs or targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs), did not significantly affect the DRR (p = 0.349). Multivariate analysis found no independent predictors of drug discontinuation. The most frequent AEs leading to discontinuation were skin reactions; no severe infections were observed. In our real-world study, comorbidities, disease duration, and previous therapies did not affect the DRR of ixekizumab. Ixekizumab had a favorable safety profile, with no severe AEs observed.

Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort

BackgroundInception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying...

Ultrasound imaging for sternoclavicular joint involvement in enthesitis-related arthritis: A closer look at capsular enthesitis

Introduction: Enthesitis-related arthritis is a specific subtype of juvenile idiopathic arthritis characterised by the co-presence of arthritis and enthesitis or the evidence of one of them coupled with at least two among sacroiliac joint tenderness, inflammatory back pain, presence of human leukocyte antigen-B27, acute symptomatic anterior uveitis, onset in a male child aged 6 years or older or history of spondyloarthropathy in a first-degree relative. Small joints like the sternoclavicular joint are rarely affected, and the prevalence of their involvement in enthesitis-related arthritis has been poorly assessed in the pertinent literature. Case report: The authors report an atypical case of left sternoclavicular joint arthritis/enthesitis in a 12-year-old male child with juvenile idiopathic arthritis. The B-mode sonographic findings of articular effusion, synovial hypertrophy and capsular bulging, coupled with the microvascular mapping with colour Doppler of the sternoclavicular joint, have been crucial to optimising the pharmacological approach in clinical practice. In this sense, the sonographic examination presented as a natural extension of the physical examination to accurately define the poor control of disease activity using first-line pharmacological agents. Discussion: The present case report can be considered the first to accurately report the B-mode and the colour Doppler findings of a pathological sternoclavicular joint in a patient enthesitis-related arthritis. Ultrasound imaging demonstrated intra-articular effusion, capsular bulging and synovial hypertrophy clearly defining sternoclavicular joint arthritis. Interestingly, the hypervascularisation involved both the synovial tissue and the capsule–bone interface – that is, the enthesis of the joint capsule – suggesting a potential co-existence of arthritis and enthesitis of the sternoclavicular joint in enthesitis-related arthritis patients. Conclusion: The high-resolution point-of-care ultrasound seems to be a potential ‘game changer’ in paediatrics to promptly optimise the pharmacological management in enthesitis-related arthritis patients. Indeed, unlike other imaging modalities such as magnetic resonance imaging, modern high-frequency ultrasound transducers guarantee a superior spatial resolution of superficial joints and allow an accurate mapping of small-size and low-flow vascular elements of synovial and capsular tissues optimising the grading of disease activity and avoiding the use of contrast agent.

Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning.

Human leucocyte antigen class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, several HCMV-encoded immunoevasins employ diverse strategies to target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While it was reported that US10 interferes with HLA-G expression, its ability to manipulate classical HLA-I antigen presentation remains unknown. In this study, we demonstrate that US10 recognizes and binds to all HLA-I (HLA-A, -B, -C, -E, -G) heavy chains. Additionally, impaired recruitment of HLA-I to the peptide loading complex was observed. Notably, the associated effects varied significantly dependending on HLA-I genotype and allotype: (i) HLA-A molecules evaded downregulation by US10, (ii) tapasin-dependent HLA-B molecules showed impaired maturation and cell surface expression, and (iii) β2m-assembled HLA-C, in particular HLA-C*05:01 and -C*12:03, and HLA-G were strongly retained in complex with US10 in the endoplasmic reticulum. These genotype-specific effects on HLA-I were confirmed through unbiased HLA-I ligandome analyses. Furthermore, in HCMV-infected fibroblasts inhibition of overlapping US10 and US11 transcription had little effect on HLA-A, but induced HLA-B antigen presentation. Thus, the US10-mediated impact on HLA-I results in multiple geno- and allotypic effects in a so far unparalleled and multimodal manner.