Artificial intelligence improves the diagnosis of human leukocyte antigen (HLA)-B27-negative axial spondyloarthritis based on multi-sequence magnetic resonance imaging and clinical features.

Background: Axial spondyloarthritis (axSpA) is frequently diagnosed late, particularly in human leukocyte antigen (HLA)-B27-negative patients, resulting in a missed opportunity for optimal treatment. This study aimed to develop an artificial intelligence (AI) tool, termed NegSpA-AI, using sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and clinical SpA features to improve the diagnosis of axSpA in HLA-B27-negative patients. Methods: We retrospectively included 454 HLA-B27-negative patients with rheumatologist-diagnosed axSpA or other diseases (non-axSpA) from the Third Affiliated Hospital of Southern Medical University and Nanhai Hospital between January 2010 and August 2021. They were divided into a training set (n=328) for 5-fold cross-validation, an internal test set (n=72), and an independent external test set (n=54). To construct a prospective test set, we further enrolled 87 patients between September 2021 and August 2023 from the Third Affiliated Hospital of Southern Medical University. MRI techniques employed included T1-weighted (T1W), T2-weighted (T2W), and fat-suppressed (FS) sequences. We developed NegSpA-AI using a deep learning (DL) network to differentiate between axSpA and non-axSpA at admission. Furthermore, we conducted a reader study involving 4 radiologists and 2 rheumatologists to evaluate and compare the performance of independent and AI-assisted clinicians. Results: NegSpA-AI demonstrated superior performance compared to the independent junior rheumatologist (≤5 years of experience), achieving areas under the curve (AUCs) of 0.878 [95% confidence interval (CI): 0.786-0.971], 0.870 (95% CI: 0.771-0.970), and 0.815 (95% CI: 0.714-0.915) on the internal, external, and prospective test sets, respectively. The assistance of NegSpA-AI promoted discriminating accuracy, sensitivity, and specificity of independent junior radiologists by 7.4-11.5%, 1.0-13.3%, and 7.4-20.6% across the 3 test sets (all P<0.05). On the prospective test set, AI assistance also improved the diagnostic accuracy, sensitivity, and specificity of independent junior rheumatologists by 7.7%, 7.7%, and 6.9%, respectively (all P<0.01). Conclusions: The proposed NegSpA-AI effectively improves radiologists' interpretations of SIJ MRI and rheumatologists' diagnoses of HLA-B27-negative axSpA.

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 monoarthritis What 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.

An Uncommon Association: HLA-B27 Positivity in Conjunction With Pernicious Anemia - A Case Report and Literature Review.

Pernicious anemia, stemming from Vitamin B12 deficiency and autoimmune processes affecting intrinsic factor production, presents challenges in early diagnosis due to vague initial symptoms. This case report introduces a unique occurrence of pernicious anemia-induced peripheral neuropathy in a patient with concurrent HLA-B27 arthropathy, highlighting the complex interplay of autoimmune mechanisms. While HLA-B27 is not typically associated with pernicious anemia, the case underscores the importance of exploring specific HLA haplotypes in understanding the nuanced manifestation of autoimmune disorders. Comprehensive screening for anti-intrinsic factor and anti-parietal cell antibodies is crucial in individuals with signs of pernicious anemia, especially those with a history of HLA-B27 arthropathy, guiding tailored management strategies. This report contributes to the ongoing exploration of the intricate autoimmune landscape in pernicious anemia.

HLA-B5 prevalence in patients with spondyloarthritis and impact on disease phenotype: a multicentric case-control study.

OBJECTIVE: The study aimed to estimate the prevalence of HLA-B51 and HLA-B52 in Lebanese patients with spondyloarthritis (SpA) compared to healthy controls (HC). We further aimed to evaluate the impact of HLA-B51 on phenotype and identify the distribution of the alleles in the HLA-B locus. METHODS: A case-control study enrolled consecutive SpA patients from three rheumatology clinics in Lebanon, including axial (axSpA), peripheral SpA (pSpA), and psoriatic arthritis (PsA) and HC from blood donors. Demographic and disease data were collected through interviews and file reviews, with testing of the entire HLA-B locus using molecular techniques. The prevalence of HLA-B51 and B52 was estimated in SpA patients versus controls. Prevalence comparisons were made, and logistic regression identified factors associated with HLA-B51 in patients. RESULTS: Data from 120 HC and 86 SpA patients (65 axSpA, 15 pSpA, 6 PsA), mean age 25.6 and 46.4 years, respectively, showed a higher HLA-B51 prevalence in SpA (25.6%), especially axSpA (29.2%) versus HC (12.5%), p = 0.016, and a numerically higher HLA-B52 prevalence (8.1% versus 4.2%, p = 0.230). HLA-B51 correlated with recurrent oral ulcerations (OR 7.99(95%CI 2.14-29.84) and radiographic juxta-articular erosions (OR 7.65(95%CI 1.14-38.03)). HLA-B35 was the most dominant allele in both groups (18.7%), followed by HLA-B27 (15.7%) and HLA-B51 (13.4%) in SpA. CONCLUSION: HLA-B51 was identified more frequently in patients with SpA compared to HC and was associated with recurrent oral ulcerations and juxta-articular radiographic erosions. Longitudinal studies are needed to determine whether this association indicates a disease overlap or might correlate with a specific SpA phenotype.

Identification of the novel HLA-B*27:276 allele by next-generation sequencing.

The novel HLA-B*27:276 allele differs from HLA-B*27:05:02:05 by one nucleotide substitution in exon 1.

TGFß signaling pathway is altered by HLA-B27 expression, resulting in pathogenic consequences relevant for spondyloarthritis.

BACKGROUND: Association of HLA-B27 with spondyloarthritis (SpA) has been known for 50 years, but still remains unexplained. We recently showed that HLA-B27 expressed in wing imaginal disc from HLA-B27/human-ß2 microglobulin (hß2m) transgenic Drosophila deregulated bone morphogenetic protein (BMP) pathway by interacting physically with type I BMP receptor (BMPR1) Saxophone (Sax), leading to crossveinless phenotype. METHODS: Genetic interaction was studied between activin/transforming growth factor ß (TGFß) pathway and HLA-B27/hß2m in transgenic Drosophila wings. The HLA-B27-bound peptidome was characterized in wing imaginal discs. In mesenteric lymph node (mLN) T cells from HLA-B27/hß2m rat (B27 rat), physical interaction between HLA-B27 and activin receptor-like kinase-2 (ALK2), ALK3 and ALK5 BMPR1s, phosphorylation of small mothers against decapentaplegic (SMADs) and proteins of the non-canonical BMP/TGFß pathways induced by its ligands, and the transcript level of target genes of the TGFß pathway, were evaluated. RESULTS: In HLA-B27/hß2m transgenic Drosophila, inappropriate signalling through the activin/TGFß pathway, involving Baboon (Babo), the type I activin/TGFß receptor, contributed to the crossveinless phenotype, in addition to deregulated BMP pathway. We identified peptides bound to HLA-B27 with the canonical binding motif in HLA-B27/hß2m transgenic Drosophila wing imaginal disc. We demonstrated specific physical interaction, between HLA-B27/hß2m and mammalian orthologs of Sax and Babo, i.e. ALK2 and ALK5 (i.e. TGFß receptor I), in the mLN cells from B27 rat. The magnitude of phosphorylation of SMAD2/3 in response to TGFß1 was increased in T cells from B27 rats, showing evidence for deregulated TGFß pathway. Accordingly, expression of several target genes of the pathway was increased in T cells from B27 rats, in basal conditions and/or after TGFß exposure, including Foxp3, Rorc, Runx1 and Maf. Interestingly, Tgfb1 expression was reduced in naive T cells from B27 rats, even premorbid, an observation consistent with a pro-inflammatory pattern. CONCLUSIONS: This study shows that HLA-B27 alters the TGFß pathways in Drosophila and B27 rat. Given the importance of this pathway in CD4 + T cells differentiation and regulation, its disturbance could contribute to the abnormal expansion of pro-inflammatory T helper 17 cells and altered regulatory T cell phenotype observed in B27 rats.

Choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis.

PURPOSE: To quantitatively analyze choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis. STUDY DESIGN: A retrospective study. METHODS: Medical records of 51 eyes with unilateral HLA-B27-associated anterior uveitis, their fellow eyes and 47 sex and age-matched healthy eyes were retrospectively reviewed. Their choroidal and retinal vasculature were analyzed using swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) scans. RESULTS: Deep capillary plexus (DCP) vessel density (VD) (p < 0.001), choroidal vascularity index (CVI) (p = 0.012), and choriocapillary flow deficit (CCFD) (p < 0.001) of uveitic and fellow eye group were significantly higher than those of control group. On the contrary, superficial capillary plexus (SCP) VD (p < 0.001) of uveitic and fellow eye group were significantly lower than of control group. The vascular parameters of uveitis and fellow eye group showed no significant difference between uveitic and resolution period. CONCLUSION: Certain choroidal and retinal vascular parameters were significantly changed in both HLA-B27-associated anterior uveitis without posterior segment involvement and the quiet fellow eyes, suggesting their possible effects as a systemic inflammatory disorder.

Looking back on 51 years of the Carol Nachman Prize in Rheumatology-significance for the field of spondyloarthritis research.

The city and casino of Wiesbaden, capital of the German state Hessen, have endowed the Carol Nachman Prize to promote research work in the field of rheumatology since 1972. The prize, endowed with 37,500 €, is the second highest medical award in Germany and serves to promote clinical, therapeutic, and experimental research work in the field of rheumatology. In June 2022, the 50-year anniversary was celebrated. In the symposium preceding the award ceremony, an overview was given on the significance of spondyloarthritis for the work of the awardees in the past 30 years. This overview has now been put together to inform the interested community of the work performed, including the opinion of the awardees regarding what they consider to be their most important contribution.

Clinical Characteristics of HLA-B27-Associated Anterior Uveitis in a Finnish Population-Based Cohort.

PURPOSE: To evaluate the clinical characteristics, treatment outcomes and ocular complications in patients with HLA-B27-associated AU compared to those without HLA-B27. METHODS: From the population-based data of all adult patients with AU during 2009-2020 (n = 413), 241 patients tested for HLA-B27 were included. Age of the initial onset, gender, etiology, course of uveitis, visual outcomes and complications were studied. RESULTS: 170 patients (71%) were HLA-B27+ and 71 (29%) HLA-B27-. Mean age at uveitis onset was 37 ± 13 in HLA-B27+ (95% CI, 35.4-39.3) and 43 ± 14 (95% CI, 40.3-46.4) in HLA-B27- patients (p = 0.001). Male:female ratio was 1.1:1 among HLA-B27+ and 0.58:1 (p = 0.024) in HLA-B27- patients. Most patients, 63% in HLA-B27+ and 68% in HLA-B27- had chronic uveitis. Recurrences were noted in 31% in HLA-B27+ group compared to 13%in HLA-B27-. 51% and 17% of HLA-B27+ and HLA-B27- patients, respectively, had systemic disease-associated uveitis. Etiology was Idiopathic in 44% and 69% of HLA-B27+ and HLA-B27- patients, respectively (p < 0.001). After the follow-up, +2 and -4 ETDRS letters changes were noted in HLA-B27+ and HLA-B27- patients (p = 0.005). Ocular complications developed in 43% and 47%, and surgical treatment of complications was required in 20% and 33% of patients in HLA-B27+ and HLA-B27- patients (p = 0.009). 1% (HLA-B27+) and 3% (HLA-B27-) developed visual impairment. CONCLUSION: Our results highlight the differences in the age of uveitis onset, gender distribution, course of uveitis, etiology, and treatment outcomes in HLA-B27+ and HLA-B27-uveitis. HLA-B27 seems to be associated with younger age at uveitis onset, more recurrences, systemic diseases, and better treatment outcomes with less complications.

The possible protective role of HLA B27 and relevant immune markers in Juvenile Idiopathic Arthritis patients.

Background & Objectives: JIA is a disease with different immunological characteristics and a complicated genetic foundation. HLA B27 is a risk factor for the development of JIA, and its impact on immunopathogenesis of the disease is also an area of interest. To determine whether HLA B27 and immune markers varied between JIA patients and healthy population. Methods: This comparative cross-sectional study was conducted at Immunology Department of University of Health sciences (UHS), Lahore from February 2018 till August 2021. A total of (71) JIA patients and (34) healthy controls were enrolled. B cells were enumerated by flowcytometry, ELISA was used for serum cytokines estimation and HLA B27 allele was detected by SPSS polymerase chain reaction. Results: The HLA B27 allele was significantly more in the control group than in the patient group, suggesting it is a protective allele to prevent JIA. Peripheral blood B cell counts and percentages were significantly lower in the HLA B27 positive group than in the HLA B27 negative group of control population. Serum cytokine levels were not significantly different between the HLA B27 positive and HLA B27 negative allele of the two study populations. Conclusion: In this study B cells are different between the two groups of control population however; serum cytokines are comparable between the study groups. Though, it was indicated that HLA B27 may be a preventive allele in the onset of JIA.

Uveitis and Scleritis as a Risk Factor for Mortality.

PURPOSE: Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual's first presentation with uveitis/scleritis. METHODS: A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality. RESULTS: 2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5-99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1-11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs' uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 p = 0.017). CONCLUSION: Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual's longevity.

Exploring the Pathogenesis of Spondylarthritis beyond HLA-B27: A Descriptive Review.

Spondylarthritis (SpA) is a chronic inflammatory condition that encompasses damage to the axial or peripheral skeleton, accompanied by specific extra-articular symptoms. Within this group, Ankylosing Spondylitis stands out as the hallmark member. Although the heritability of Ankylosing Spondylitis is estimated to be over 95%, only a portion of the heritability has been explained, with HLA-B27 accounting for 20.1% of it; therefore, ongoing research endeavors are currently concentrated on investigating the potential participation of different entities in the development of the disease. Genome-wide association studies have led to significant advances in our understanding of the genetics of SpA. In this descriptive review, we delve into the pathogenesis of Spondylarthritis beyond HLA-B27. We summarize the latest research on the potential participation of various entities in the development of the disease, including other genetic loci, immune dysregulation, microbiota, and environmental factors. The multifactorial nature of SpA and the complex interplay of genetic, immunological, and environmental factors are being increasingly recognized; therefore, it is of paramount importance to consider a holistic approach to comprehend the pathogenesis of SpA in order to identify novel therapeutic targets.

Comparative study of two laboratory techniques for the detection of HLA-B27 in patients with axial spondyloarthritis: a cross-sectional analysis.

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.

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.

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.

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.

Diagnosis and Treatment of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory condition primarily affecting the axial bone and sacroiliac joints. Its etiology is complicated and involves genetic variables, demographic factors (age of onset, gender, ethnicity, family history), and environmental variables. It typically manifests in males in their third decade. Galen is credited with first recognizing it, according to historical traditions, but it was not until the 19th century that specific diagnostic criteria were developed. The human leukocyte antigen B27 (HLA-B27) variation, around 20% of the genetic risk, is currently the most significant gene associated with AS susceptibility. Over 100 genes have been connected to AS susceptibility. Clinical signs of AS include stiffness and inflammation in the back, eye inflammation, aortitis (inflammation of the aorta), and spinal ankylosis that impacts posture and fatigue. The dagger sign and sacroiliitis on radiographs, in particular, are crucial for diagnosis. Early inflammatory alterations can be found using modern diagnostic tools such as MRI, and the HLA-B27 gene can help confirm the diagnosis. Overall, 80-95% of people with AS have the HLA-B27 marker. Furthermore, although non-specific, elevated inflammatory markers, such as C-reactive protein and erythrocyte sedimentation rate, offer supporting evidence. Over time, treatment paradigms have seen significant change. First-line treatments such as non-steroidal anti-inflammatory drugs are no longer the only options, even though disease-modifying anti-rheumatic drugs and biologics, especially tumor necrosis factor blockers, have been developed. Physical therapy, which emphasizes consistent exercise, stretches, and posture maintenance, is extremely helpful in managing AS. Surgical interventions can be required in extreme situations. The significance of the interleukin 23/17 axis in the disease cascade has been demonstrated by recent research. Furthermore, a deeper comprehension of the genetic landscape, mainly the functions of non-HLA-B27 loci, may open the door for more specialized therapies. Early diagnosis and interdisciplinary therapies can improve patient outcomes and quality of life as our understanding of AS grows.

Enhancing HLA-B27 antigen detection: Leveraging machine learning algorithms for flow cytometric analysis.

As the association of human leukocyte antigen B27 (HLA-B27) with spondylarthropathies is widely known, HLA-B27 antigen expression is frequently identified using flow cytometric or other techniques. Because of the possibility of cross-reaction with off target antigens, such as HLA-B7, each flow cytometric technique applies a "gray zone" reserved for equivocal findings. Our aim was to use machine learning (ML) methods to classify such equivocal data as positive or negative. Equivocal samples (n = 99) were selected from samples submitted to our institution for clinical evaluation by HLA-B27 antigen testing. Samples were analyzed by flow cytometry and polymerase chain reaction. Features of histograms generated by flow cytometry were used to train and validate ML methods for classification as logistic regression (LR), decision tree (DT), random forest (RF) and light gradient boost method (GBM). All evaluated ML algorithms performed well, with high accuracy, sensitivity, specificity, as well as negative and positive predictive values. Although, gradient boost approaches are proposed as high performance methods; nevertheless, their effectiveness may be lower for smaller sample sizes. On our relatively smaller sample set, the random forest algorithm performed best (AUC: 0.92), but there was no statistically significant difference between the ML algorithms used. AUC values for light GBM, DT, and LR were 0.88, 0.89, 0.89, respectively. Implementing these algorithms into the process of HLA-B27 testing can reduce the number of uncertain, false negative or false positive cases, especially in laboratories where no genetic testing is available.

Targeted therapies for uveitis in spondyloarthritis: A narrative review.

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.

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.