The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study.

BACKGROUND: The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. METHODS: The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. RESULTS: Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test). CONCLUSION: In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.

Differences between radiographic and non-radiographic axial spondyloarthritis patients in a Mexican cohort.

To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3-85), HLA-B27 (OR 7.97, 95% CI, 2.96-122), male sex (OR 6.16, 95% CI, 1.47-25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03-1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

Clinical, Laboratory, and Imaging Features Between Men and Women With Axial Spondyloarthritis in a Specialized Center in Argentina.

OBJECTIVES: The aims were to estimate the frequency of axial spondyloarthritis (axSpA) in women and to analyze the clinical, laboratory, and imaging differences with respect to men at the time of diagnosis. METHODS: Consecutive patients older than 18 years with a diagnosis of axSpA admitted to the "Reumacheck" SpA program were included between 2017 and 2022. At baseline, all patients underwent clinical assessment, laboratory tests including C-reactive protein and human leukocyte antigen B27, and imaging (plain radiography and magnetic resonance imaging of sacroiliac joints, and ultrasound of heel entheses). All evaluators were blinded to the results of the other evaluations. RESULTS: One hundred sixteen patients with a diagnosis of axSpA were included. The frequency at diagnosis in women was 61.55%. In the univariate analysis, the significant differences between women and men at diagnosis of axSpA were good response to nonsteroidal anti-inflammatory drugs, elevated C-reactive protein, New York Criteria (+), enthesis ultrasound (+), years of education, number of swollen joints, erythrosedimentation rate, and the very low frequency of bone bridges in the magnetic resonance imaging of the sacroiliac joints. In the logistic regression analysis, the dependent variable was "men," and the only feature that was independently associated was having radiographic compromise according to the New York criteria (odds ratio, 2.6). CONCLUSIONS: The frequency of axSpA in women was 61.55%; clinical, laboratory, and imaging differences were observed. Women experienced less radiographic compromise.

Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09-2.11, corrected p [pc] = .028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13-2.34, pc = .016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12-2.28, pc = .018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

Long-term follow-up of 109 children with juvenile idiopathic oligoarthritis after first intra-articular corticosteroid injection.

BACKGROUND: To evaluate long-term outcomes and prognostic factors in patients with juvenile idiopathic arthritis (JIA), presenting as oligoarthritis, who received IAC as the first treatment for their disease. METHODS: We conducted retrospective study at the University Children's Hospital Ljubljana, Slovenia, from January 2015 to May 2023 in children with JIA, clinically presenting as oligoarthritis receiving intra-articular corticosteroid injection (IAC) as the initial treatment. Patient and treatment data were collected, and the outcomes were categorized into three groups based on the later need for therapy: no therapy needed, only additional IAC needed and systemic therapy needed. The last group was further divided based on the requirement of bDMARD. Log-rank (Mantel-Cox) survival analyses compared different outcome groups. RESULTS: We included 109 patients with JIA, presenting as oligoarthritis (63% female), who were first treated with IAC. The mean age at IAC was 8.0 years, with a 4.3-year follow-up. Notably, 38.5% of patients did not require additional therapy post-IAC, whereas 15.5% required only additional IAC. Systemic therapy, mainly methotrexate (MTX), was necessary for 45.9% of patients, initiated in average 7.8 months post-IAC. Biologic therapy was initiated in 22% in average 2.2 years post-IAC. Number of injected joints correlated with the need for biologics. At the last follow-up, 88.9% had inactive disease. ANA positivity (P = 0.049, chi square 3.89) and HLA B27 antigen presence (P = 0.050, chi square 3.85) were associated with the need for systemic therapy. A subgroup of children older than 8 years, ANA and HLA B27 negative required significantly less systemic (25.8%) and biologic therapy (9.6%) compared to other patients (p = 0.050, chi square 3.77). CONCLUSION: Almost 40% of children with oligoarticular JIA requiring IAC did not progress to chronic disease. Younger age, ANA positivity, and HLA B27 presence were predictive factors for systemic therapy, while the number of injected joints predicted the future need for biologic therapy.

Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics.

BACKGROUND: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. METHODS: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. RESULTS: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. CONCLUSIONS: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.

How to translate genetic findings into clinical applications in spondyloarthritis?

Spondyloarthritis (SpA) is characterized by a strong genetic predisposition evidenced by the identification of up to 50 susceptibility loci, in addition to HLA-B27, the major genetic factor associated with the disease. These loci have not only deepened our understanding of disease pathogenesis but also offer the potential to improve disease management. Diagnostic delay is a major issue in SpA. HLA-B27 testing is widely used as diagnostic biomarker in SpA but its predictive value is limited. Several attempts have been made to develop more sophisticated polygenic risk score (PRS). However, these scores currently offer very little improvement as compared to HLA-B27 and are still difficult to implement in clinical routine. Genetics might also help to predict disease outcome including treatment response. Several genetic variants have been reported to be associated with radiographic damage or with poor response to TNF blockers, unfortunately with lack of coherence across studies. Large-scale studies should be conducted to obtain more robust findings. Genetic and genomic evidence in complex diseases can be further used to support the identification of new drug targets and to repurpose existing drugs. Although not fully driven by genetics, development of IL-17 blockers has been facilitated by the discovery of the association between IL23R variants and SpA. Development of recent approaches combining GWAS findings with functional genomics will help to prioritize new drug targets in the future. Although very promising, translational genetics in SpA remains challenging and will require a multidisciplinary approach that integrates genetics, genomics, immunology, and clinical research.

Anti-HLA-B7/HLA-B44 strong cross immunoreactivity observed in flow cytometry HLA-B27 immunotyping.

Cross reactivities are known for human leukocyte antigen inside HLA-B7 related Cross-Reactive Group (B7CREG). Some CE-IVD flow-cytometry kits use double monoclonal antibodies (mAb) to distinguish HLA-B27 and HLA-B7 but practice reveals more complexes results. This study explores the performances of this test. Analysis of 466 consecutive cases using HLA-B27 IOTest™ kit on a Navios™ cytometer from Beckman-Coulter, partially compared to their genotypes. Expected haplotypes HLA-B27-/HLA-B7- (undoubtedly HLA-B27 negative) and HLA-B27+/HLA-B7- (undoubtedly HLA-B27+) were clearly identified according to the manufacturer's instructions. On the opposite, patients strongly labeled with anti-HLA-B7 showed three different phenotypes regarding anti-HLA-B27 labeling: (1) most of the cases were poorly labeled in accordance with cross reactivity inside B7CREG (HLA-B27-/HLA-B7+ haplotype); (2) rare cases had strong B7 and B27 labeling corresponding to HLA-B27+/HLA-B7+ haplotype; (3) even less cases had strong labeling by anti-HLA-B7 but non for anti-HLA-B27, all expressing HLA-B44 and no B7CREG molecules. Surprisingly, more cases were not labeled with anti-HLA-B7 antibody but partially labeled with anti-HLA-B27 suggesting another cross reactivity out of B7CREG. mAb HLA typing suggests new, cross reactivities of anti-HLA-B27 antibody to more molecules out of B7CREG and of anti-HLA-B7 antibody but not anti-HLA-B27 to HLA-B44 molecule also out of B7CREG. HLA-B27 could surely be excluded in most samples labeled with HLA-B27, below a "grey zone" on intermediate intensity. More comparison is needed in future studies.

Profile of HLA-B27-positive enthesitis/spondylitis-related arthritis in Senegal, West Africa.

BACKGROUND: Enthesitis/spondylitis-related arthritis (ERA) is a type of juvenile idiopathic arthritis (JIA) frequently associated with HLA-B27. In sub-Saharan Africa, HLA-B27-positive ERA hasn't been the subject of a specific study. OBJECTIVES: We aimed to describe the clinical features, disease activity, functional disability and treatment of HLA-B27-positive ERA at diagnosis in Senegal and compare the findings to other populations. METHODS: We conducted a retrospective study by reviewing the medical records of patients diagnosed with ERA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for ERA from January 2012 to December 2022. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional disability was assessed using Bath Ankylosing Spondylitis Functional Index (BASFI). RESULTS: A total of 31 patients with HLA-B27-positive ERA were included. Twenty of 31 (64.5%) were males. Twenty-seven (87%) were Fula (ethnicity). The median age at symptom onset and at diagnosis was 12 years and 19 years, respectively. Seven patients had a family history of Spondyloarthritis. Peripheral arthritis and enthesitis were the most common presenting features at disease onset. Peripheral arthritis was present in 29 (93.5%) and located in the lower limbs in 27/29 (93.1%) patients. Heel enthesitis was present in 26 (83.8%) patients. Axial involvement was present in 27 (87%) patients, dominated by low back pain and sacroiliac pain/ buttock pain in 24 (88.8%) and 22 (81.5%) patients, respectively. Seven (22.5%) patients had anterior uveitis. The ESR and CRP were elevated in 65.5% and 57.1% of cases, respectively. On imaging, sacroiliitis was found in 22 patients. The mean BASDAI was 5.5/10 (77.2% of patients had a high active disease; BASDAI ≥ 4/10). The mean ASDAS-ESR/CRP was 3.8. The mean BASFI was 5.4/10 (80% of patients had high functional disability; BASFI ≥ 4/10). Twenty-seven (87%) patients were treated with methotrexate and non-steroidal anti-inflammatory drugs. After 6 months of treatment, mean BASDAI was 3/10 and mean BASFI was 2.5/10. CONCLUSION: In our study, HLA-B27-positive ERA was found in our Senegalese cohort mainly in adolescents of the Fula ethnic group. 22 (70.9%) patients developed ankylosing spondylitis at adulthood. The disease was very active at the time of diagnosis with significant functional disability. Treatment was mainly based on methotrexate and NAISDs.

Changes in HLA-B27 Transgenic Rat Fecal Microbiota Following Tofacitinib Treatment and Ileocecal Resection Surgery: Implications for Crohn's Disease Management.

The therapeutic management of Crohn's disease (CD), a chronic relapsing-remitting inflammatory bowel disease (IBD), is highly challenging. Surgical resection is sometimes a necessary procedure even though it is often associated with postoperative recurrences (PORs). Tofacitinib, an orally active small molecule Janus kinase inhibitor, is an anti-inflammatory drug meant to limit PORs in CD. Whereas bidirectional interactions between the gut microbiota and the relevant IBD drug are crucial, little is known about the impact of tofacitinib on the gut microbiota. The HLA-B27 transgenic rat is a good preclinical model used in IBD research, including for PORs after ileocecal resection (ICR). In the present study, we used shotgun metagenomics to first delineate the baseline composition and determinants of the fecal microbiome of HLA-B27 rats and then to evaluate the distinct impact of either tofacitinib treatment, ileocecal resection or the cumulative effect of both interventions on the gut microbiota in these HLA-B27 rats. The results confirmed that the microbiome of the HLA-B27 rats was fairly different from their wild-type littermates. We demonstrated here that oral treatment with tofacitinib does not affect the gut microbial composition of HLA-B27 rats. Of note, we showed that ICR induced an intense loss of bacterial diversity together with dramatic changes in taxa relative abundances. However, the oral treatment with tofacitinib neither modified the alpha-diversity nor exacerbated significant modifications in bacterial taxa induced by ICR. Collectively, these preclinical data are rather favorable for the use of tofacitinib in combination with ICR to address Crohn's disease management when considering microbiota.

Prevalence of HLA B27 in Patients Diagnosed with Ankylosing Spondylitis (AS) in Diyarbakir, Southeastern Region of Turkey.

AIM: The research to be conducted on human leukocyte antigen (HLA)-B27 in patients diagnosed with ankylosing spondylitis (AS) in Diyarbakir between 2019-2021 is to contribute to the understanding of the prevalence and effect of this genetic marker in the local population. As a researcher working on HLA-B27 and AS, our focus is to research the following. HLA-B27 Prevalence: To determine the prevalence of HLA-B27 in patients diagnosed with AS during the specified period in Diyarbakir. This information can provide insight into the genetic factors associated with the disease in the local population. Disease Severity: Investigate the relationship between HLA-B27 positivity and severity of AS symptoms. To examine factors such as disease progression, pain levels, functional impairment, and quality of life in HLA-B27 positive patients compared to HLA-B27 negative patients. By Genetic Associations: To enable the discovery of potential genetic relationships between HLA-B27 and other genetic markers known to be associated with AS. To investigate whether there are any specific genetic variants associated with HLA-B27 that contribute to disease susceptibility or severity. Researchers: We recommend considering the following approaches to generate knowledge on this topic globally: Literature Review: Conducting a comprehensive review of the available scientific literature on HLA-B27 and AS. It is to describe relevant studies conducted globally and summarize their findings to provide a broader understanding of the subject. Collaboration and Data Sharing: To encourage cooperation with researchers from other regions or countries doing similar studies on HLA-B27 and ASs. By sharing our data and collaborating on analysis, we can improve the global perspective and generalizability of your findings. International Conferences and Journals: Presenting our research findings at international conferences focusing on rheumatology, genetics or related fields. To disseminate our findings globally is to submit your research articles to reputable journals specializing in AS or genetic studies. Online Platforms: Using online platforms such as Researchgate.net, academia.edu or social media networks to share our research findings, connect with other researchers in the field and participate in discussions on a global scale. By using these fields, it is possible to contribute to the global knowledge and understanding of the relationship between HLA-B27 and AS. It is also to obtain insights from studies carried out in other regions. MATERIALS AND METHODS: 198 (104 male and 94 female) patients who applied to Dicle University Faculty of Medicine Physical Therapy and Rehabilitation Clinic with AS symptoms between 2019-2021 and were referred to Dicle University Medical Biology and Genetics Department for evaluation. HLA-B27 positivity was included in our study as a case group. As the control group, 50 people (25 males, 25 females) were selected among the unrelated people who applied to our laboratory to be a bone marrow donor. In both groups, DNA isolation was performed from peripheral blood using the salt precipitation method. Rotar Gene Q device was used for real-time PCR analysis. As a statistical method in analysis; The prevalences of the variables of interest were calculated. The lower and upper limits of 95% were determined as the confidence interval. According to the presence of HLA 27 positivity, the mean of ESR, CRP, and age variables were compared. Mann-Whitney U test was used due to the small number of subjects. Also, correlations between ESR and CRP were calculated. Spearman rho correlation statistics were used as a statistical method. Analyzed. RESULT: Radiological examinations and laboratory tests were performed on 198 patients with suspicion AS and 50 healthy control group of 248 subjects. The prevalence of those with a definite diagnosis of AS was calculated as statistical analysis recalculated 20.16 (95% CI: 0.76-0.9552). The prevalence of HLA-B27 in 50 patients diagnosed with AS as a result of radiological examinations and laboratory tests was calculated as 92%. CONCLUSION: Our study is the first study covering the province of Diyarbakir in the Southeastern Anatolia Region, which we think will contribute to the literature in the evaluation of HLA-B27 positivity in AS patients. The prevalence of HLA-B27 in our region is higher than the prevalence in Turkey.

Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. METHODS: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). MAIN OUTCOME: axSpA diagnosis with LoC≥7 (d-axSpA) at 2y. RESULTS: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. CONCLUSION: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients.

HLA-B*58 and HLA-B*27 Play a Role in the Development of Acute Leukemia: A Case Control Study.

BACKGROUND: Acute leukemia (AL) constitutes a group of malignant hematological diseases with multifactor origins. Some human leukocyte alleles (HLA) may be important genetic risk factors for development of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It is still unknown whether there is a relationship between ALL and AML with some alleles of the major histocompatibility complex. Our study looks specifically at western and southwest Algerian populations. METHOD: Using the polymerase chain reaction with the sequence specific probe (PCR- SSP) method, we investigated the relationship of HLA-B alleles in 163 Algerian AL patients and 293 controls from the same ethnic origin. The study ran from 2013 - 2020. RESULTS: Allele frequencies of HLA-B*27 and HLA-B*58 was higher in AL patients compared with control individuals; p=0.05 and p=0.03 respectively. Interestingly, all patients carrying HLA-B*27 allele and 88% of patients carrying HLA-B*58 allele had AML. However, there were no significant differences when we compared these results with the rest of AL group (HLA-B*X allele) (p=0.387). Response to induction chemotherapy treatment were comparable between the two patient groups 67% and 65% (p=0.978) respectively. CONCLUSION: These results suggest that the HLA-B*27 and HLA-B*58, may be factors predisposing individuals to acute leukemia, in west and southwest Algerian patients. A large-scale study is still needed to confirm these findings.

Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases.

Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.

Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance.

BACKGROUND: NAT10 is the firstly recognized RNA acetyltransferase that participates in multiple cellular biological processes and human disease. However, the role of N-acetyltransferase 10 (NAT10) in ankylosing spondylitis (AS) is still poorly elaborated. METHODS: Fifty-six patients with New-Onset AS, 52 healthy controls (HC), 20 patients with rheumatoid arthritis (RA) and 16 patients with systemic lupus erythematosus (SLE) were recruited from The First Afliated Hospital of Nanchang University, and their clinical characteristics were recorded. The expression level of NAT10 in peripheral blood mononuclear cell (PBMC) was examined using reverse transcription-quantitative PCR analysis. The correlations between the expression level of NAT10 in the New-Onset AS patients and disease activity of AS were examined, and receiver operating characteristic (ROC) curves were built to evaluate predictive value in AS. Univariate analysis and multivariate regression analysis were used to analyze the risk factors and construct predictive model. RESULTS: The mRNA expressions of NAT10 in PBMC from new-onset AS patients were significantly low and there were negative correlation between mRNA NAT10 and ASDAS-CRP, BASDIA in new-onset AS patients. ROC analysis suggested that mRNA NAT10 has value in distinguishing new-onset AS patients from HC, RA and SLE. Furthermore, a novel predictive model based on mRNA NAT10 and neutrophil percentages (N%) was constructed for distinguishing new-onset AS patients from HC (AUC = 0.880, sensitivity = 84.62%, specificity = 76.92%) and the predictive model correlated with the activity of new-onset AS. Furthermore, the predictive model could distinguish new-onset AS patients from RA and SLE (AUC = 0.661, sensitivity = 90.38%, specificity = 47.22%). Moreover, the potential predictive value of the combination of predictive model-HLA-B27 for AS vs. HC with a sensitivity of 92.86% (39/42), a specificity of 100.00% (52/52) and an accuracy of 96.81% (91/94) was superior to that of HLA-B27, which in turn had a sensitivity of 84.44% (38/45), a specificity of 100.00% (52/52) and an accuracy of 92.78% (90/97). CONCLUSION: The present study suggested that the decreased mRNA NAT10 may play a role in AS pathogenesis and predictive model based on mRNA NAT10 and N% act as bioindicator for forecast and progression of diseases.

The Presence of Pigmentation on Central Anterior Lens Capsule in the Human Leukocyte Antigen B27-Associated Anterior Uveitis and Its Value in Clinical Diagnosis.

PURPOSE: To report on the value of presence of pigmentation on central anterior lens capsule (PioLe) in HLA B27- associated anterior uveitis (HLA B27-AU). METHODS: 268 patients (320 eyes) with AU were reviewed. Two diagnostic models to predict probability of HLA-B27-AU were developed. The first model included 6 variables (age, gender, unilaterality, presence of non-granulomatous keratic precipitates, hypopyon, and intraocular pressure (IOP). The second model was developed to investigate the added value of PioLe into the first model. RESULTS:      Unilaterality, presence of hypopyon, IOP <21 mmHg and PioLe were characteristic for HLA-B27 positive patients (P≤0.003 for all). All of 6 variables had area under receiver operating characteristic curves (AuROC) ≤ 60, but PioLe reached even higher value (65.5). Diagnostic model I and II had AuROC 76.3% (95%CI, 68.4%-84.2%) and 80.0% (95%CI, 72.6%-87.5%), respectively. CONCLUSIONS: Unilaterality, hypopyon, IOP <21 mmHg and presence of PioLe are clinical signs suggesting HLA B27- AU.

Diagnosis, Treatment, and Prevention of Noninfectious Acute Anterior Uveitis with or without Human Leukocyte Antigen B27 in Adults - Expert Consensus in Taiwan.

BACKGROUND: Anterior uveitis is the most common anatomical type of uveitis. Patients with noninfectious anterior uveitis may develop various ocular complications and eventually visual impairment. Appropriately differentiating the etiologies can help clinicians to predict the outcome, arrange clinical follow-up, and decide the treatment or prevention strategy. Adequate treatment and effective prevention strategies can reduce the frequency of recurrence and the risk of developing complications. Human leukocyte antigen (HLA)-B27 is the most common positive finding in patients with noninfectious AAU in many countries including Taiwan. PURPOSE: To report a consensus from experienced uveitis specialists and rheumatologists was made in Taiwan. METHODS: A panel of nine ophthalmologists from nine different referral centers with expertise in the management of uveitis and an experienced rheumatologist was held on January 16, 2022. A comprehensive literature review was performed. Differential diagnoses for etiologies, general treatments, and prevention strategies were discussed. Each statement in the consensus was made only if more than 70% of the experts agreed. RESULTS: A flow chart and seven statements regarding the differential diagnoses for etiologies, treatments and preventions, and co-management with rheumatologists were included in the consensus. CONCLUSIONS: This article discusses the general diagnosis, treatment, and prevention of noninfectious acute anterior uveitis, with or without HLA-B27, in adults for general ophthalmologists to improve overall outcomes of these patients.

HLA-B27-positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management, and treatment.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

A Review of Laboratory Practices Using the HLA-B27 Survey by the College of American Pathologists: How Important Is Allele-Level Typing?

CONTEXT.­: Ankylosing spondylitis (AS) is an autoimmune disorder with a strong genetic risk, especially with HLA-B27. Clinical testing for HLA-B27 has been used to help diagnose patients with signs and symptoms of AS. Testing methods used by clinical laboratories for HLA-B27 fall into the broad categories of serologic/antibody- or molecular-based methods and have evolved over time. The College of American Pathologists (CAP) offers a proficiency testing survey for HLA-B27. OBJECTIVE.­: To analyze HLA-B27 testing trends and their performance in the past decade, using the proficiency testing survey data submitted to CAP. DESIGN.­: We analyzed the HLA-B27 CAP proficiency testing data from 2010 to 2020 for the method used, participant concordance, and error rates. Results from case scenarios to understand evolving scientific data around HLA-B27 risk alleles were also analyzed. RESULTS.­: Antibody-based flow cytometry is the most common method, though it has decreased from 60% in 2010 to 52% in 2020, with a corresponding increase in molecular methods. Among the molecular methods, real-time polymerase chain reaction has increased from 2% to 15%. Flow cytometry had the highest error rate (5.33%), and sequence-specific oligonucleotide (0%) is the most accurate (0%). Results of case scenarios demonstrated that most participants understood that allele-level HLA-B27 typing results inform clinical interpretation, for example HLA-B*27:06 is not associated with AS. CONCLUSIONS.­: These data demonstrated the changing trends for HLA-B27 testing during the past decade. HLA-B27 allelic typing provides a better understanding of AS association. This is possible by testing for the second field with methods like next-generation sequencing.