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.

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.

Teste de detecção de HLA-B27para indivíduos com suspeita de espondiloartrite axial e para avaliação prognóstica da doença / HLA-B27 detection test for individuals suspected of having axial spondyloarthritis and for prognostic assessment of the disease

INTRODUÇÃO: A Espondiloartrite Axial (EpA) é uma doença inflamatória crônica, de origem autoimune, caracterizada por dor intensa, enrijecimento das articulações (anquilose) com inflamação nas inserções dos tendões, limitação funcional progressiva, provocando danos estruturais irreversíveis das articulações sacroilíacas e espinhais, que cursam com alterações radiográficas e formação óssea excessiva. O antígeno HLA-B27 está fortemente correlacionado com o aparecimento da doença e um teste positivo para esse marcador é encontrado na maioria dos casos. No Brasil, diversos estudos sugerem que os portadores do antígeno HLA-B27 representam em torno de 60-70% dos pacientes. PERGUNTA: Em indivíduos com suspeita de espondiloartrite axial, qual a sensibilidade, especificidade e utilidade diagnóstica do teste HLA-B27 em comparação aos critérios ASAS, de Nova Iorque e diagnóstico por radiologista? EVIDÊNCIAS CLÍNICAS: Nos estudos incluídos, conduzidos em sua maioria em países europeus, foram comparados o teste HLA-B27 e os critérios de diagnóstico ASAS ou Nova Iorque. A sensibilidade do teste HLA-B27 foi de 68% (IC95%: 67-69%) e a especificidade de 88% (IC95%: 87-88%). Além disso, o valor preditivo positivo do teste foi em média de 0,71 (± 0,21), enquanto o valor preditivo negativo foi em média de 0,74 (± 0,20); a razão de verossimilhança positiva e negativa foi de 4,85 (IC95% 3,83-6,14) e 0,36 (IC95% 0,29-0,45). Foram realizadas análises de subgrupo considerando os diferentes comparadores: 1) critérios de diagnóstico ASAS, a sensibilidade estimada de HLAB27 foi de 67% (IC95%: 65-69%), e a especificidade foi de 92% (IC95%: 91-92%), 2) critérios de diagnóstico Nova Iorque modificado, a sensibilidade estimada de HLA-B27 foi de 85% (IC95%: 83- 87%), e a especificidade foi de 83% (IC95%: 81-85%). A partir da análise de dois estudos, observou-se que a associação de HLA-B27 e parâmetros clínicos ainda possibilitou o alcance de uma sensibilidade e especificidade comparável ou maior do que a combinação de exame de imagem (RMN ou radiografia) e parâmetros clínicos, ou apenas os parâmetros clínicos. No geral, estes estudos foram classificados como de alto ou incerto risco de viés, especialmente no domínio "seleção dos pacientes" devido à ausência de informação sobre o processo ou por uso de amostra não randomizada/consecutiva. O alto e incerto risco de viés aliado à elevada heterogeneidade e evidência indireta foram responsáveis pela classificação da qualidade da evidência como muito baixa para sensibilidade e especificidade. AVALIAÇÃO ECONÔMICA (AE): Foi desenvolvida uma análise de custo-efetividade comparando teste HLA-B27 + avaliação clínica versus i) avaliação clínica; e ii) avaliação clínica ± sacroileíte em exame de imagem (radiografia simples ou ressonância magnética). Para ambas as comparações foi elaborada uma árvore de decisão acoplada ao modelo de estados transicionais (Markov). Na comparação com avaliação clínica, o teste HLA-B27 + avaliação clínica este próximo do limiar de custo-efetividade custo-efetivo (R$ 43 mil reais por AVAQ). Além disso, apresentou custo incremental de R$ 298 por diagnóstico correto incremental. Na comparação com avaliação clínica ± exame de imagem, o teste de HLA-B27 + avaliação clínica dominou (menor custo e maior efetividade) o comparador, e foi considerado custo-efetivo na análise de cenário considerando como desfecho e apresentou custo incremental de R$ 2 mil por diagnóstico correto incremental. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): No cenário atual foram considerados os critérios de classificação ASAS sem o teste HLA-B27 como alternativa disponível no SUS, a saber: avaliação clínica (49%) ou avaliação clínica + sacroileíte identificada por radiografia simples (49%) ou ressonância magnética (2%). O market share do cenário atual foi estabelecido com base em literatura científica, dados do Sistema de Informação Ambulatorial - produção ambulatorial e opinião de especialista. Por demanda aferida, foram estimados em torno de 15 a 18 mil indivíduos por ano com suspeita de espondiloartrite axial e 5,7 a 6,9 mil indivíduos com resultados negativos ou incerto pela avaliação clínica e de imagem. Observou-se que a incorporação de HLA-B27 no SUS para indicação proposta teria como resultado um incremento de custos de R$ 638 mil no primeiro ano, chegando a R$ 770 mil no quinto ano de análise. MONITORAMENTO DE HORIZONTE TECNOLÓGICO: Foram realizadas buscas estruturadas nas bases de dados ClinicalTrials.gov e Cortellis™ nos dias 22/11/2023 e 23/11/2023 para a localização de outros dispositivos utilizados na detecção do antígeno HLA-B27 em indivíduos com suspeita de espondiloartrite axial. As pesquisas nas bases de dados não apresentaram resultados para novos dispositivos. CONSIDERAÇÕES FINAIS: Os resultados dos parâmetros diagnósticos resultantes da utilização do teste HLA-B27 no contexto da espondiloatrite axial foram relacionados a alta grau de incerteza, o que dificulta a elaboração de conclusão mais definitivas. Nas avaliações econômicas foi demonstrado que o exame pode ser custo-efetivo, e exigirá, caso incorporado, um investimento do SUS, conforme observado na análise de impacto orçamentário. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Produtos e Procedimentos presentes na 17ª Reunião Extraordinária da Conitec, realizada no dia 08 de dezembro de 2023, deliberaram, por unanimidade, que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação do teste de detecção de HLA-B27 para indivíduos com suspeita de espondiloartrite axial, que apresentem critérios clínicos da doença e que não apresentem alterações nos exames de imagem. CONSULTA PÚBLICA: A consulta pública nº 68 ficou aberta entre 29 de dezembro de 2023 e 17 de janeiro de 2024. Foram recebidas 95 contribuições, sendo 32 de experiência ou opinião e 63 técnico-cientificas. As contribuições técnicas-cientificas concordaram com a recomendação preliminar, reforçando a importância do teste e os achados deste relatório. Não foram identificadas contribuições técnico-científicas que fundamentassem a necessidade de análises adicionais de evidência clínica, avaliação econômica e análise de impacto orçamentário. Em relação às contribuições de experiência e opinião, os participantes, em sua maioria, concordaram com a recomendação preliminar da Conitec e se posicionaram favoravelmente à incorporação, no SUS, do teste de detecção de HLA-B27, argumentando, sobretudo, sobre a acurácia do teste e seus benefícios para o diagnóstico da condição de saúde em questão. Os participantes que usaram a tecnologia em avaliação destacaram, como aspectos positivos, a acurácia do teste, a sua contribuição para fechar o diagnóstico e o fato de ser um exame não invasivo. Como aspectos negativos, foram mencionados a dificuldade de acesso e o custo elevado. Em relação à experiência com outras tecnologias, os participantes pontuaram que estas contribuíram para concluir o diagnóstico e iniciar o tratamento, contudo, apontaram como aspectos negativos a dificuldade de acesso e o tempo de espera para realizar esses exames, impossibilitando o diagnóstico. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Produtos e Procedimentos presentes na 127ª Reunião Ordinária da Conitec, realizada no dia 08 de março de 2024, deliberaram, por unanimidade, recomendar a incorporação do teste de detecção de HLA-B27 para indivíduos com suspeita de espondiloartrite axial, conforme Protocolo Clínico do Ministério da Saúde. O Comitê concluiu que o teste aumenta a acurácia quando associado a outras estratégias diagnósticas, com o potencial de ser custo-efetivo. Foi assinado o Registro de Deliberação nº 888/2024. DECISÃO: incorporar, no âmbito do Sistema Único de Saúde - SUS, o teste de detecção de HLAB27 para indivíduos com suspeita de espondiloartrite axial, conforme Protocolo Clínico do Ministério da Saúde, publicada no Diário Oficial da União nº 77, seção 1, página 177, em 22 de abril de 2024.

Axial and peripheral spondyloarthritis triggered by sars-cov-2 infection: a report of two cases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can show musculoskeletal symptoms such as peripheral arthritis. In rare cases, peripheral arthritis can develop after the resolution of SARS-CoV-2. We present two cases of spondyloarthritis induced by SARS-CoV-2; one case with axial and peripheral spondyloarthritis and the other with peripheral spondyloarthritis. Both cases refer to Lebanese patients who were HLA-B27 positive. These two cases highlight the possible predisposition of HLA-B27 positive patients to the development of spondyloarthritis symptoms triggered by SARS-CoV-2.

Axial spondyloarthritis: new advances in diagnosis and management.

Axial spondyloarthritis (axSpA) is an inflammatory disease of the axial skeleton associated with significant pain and disability. Previously, the diagnosis of ankylosing spondylitis required advanced changes on plain radiographs of the sacroiliac joints. Classification criteria released in 2009, however, identified a subset of patients, under the age of 45, with back pain for more than three months in the absence of radiographic sacroiliitis who were classified as axSpA based on a positive magnetic resonance imaging or HLAB27 positivity and specific clinical features. This subgroup was labeled non-radiographic (nr)-axSpA. These patients, compared with those identified by the older New York criteria, contained a larger percentage of women and demonstrated less structural damage. However, their clinical manifestations and response to biologics were similar to radiographic axSpA. The discovery of the interleukin (IL) IL-23/IL-17 pathway revealed key molecules involved in the pathophysiology of axSpA. This discovery propelled the generation of antibodies directed toward IL-17A, which are highly effective and demonstrate treatment responses in axSpA that are similar to those observed with anti-TNF agents. The finding that agents that block IL-23 were not effective in axSpA came as a surprise and the potential underlying mechanisms underlying this lack of response are discussed. New agents with dual inhibition of the IL-17A and F isoforms and some oral small molecule agents that target the Jak-STAT pathway, have also shown efficacy in axSpA.

Axial and peripheral spondyloarthritis: does psoriasis influence the clinical expression and disease burden? Data from REGISPONSER registry.

OBJECTIVE: To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). METHODS: Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. RESULTS: A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27+ [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27+ (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. CONCLUSION: These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

Predictive values of inflammatory back pain, positive HLA B27 antigen and acute and chronic magnetic resonance changes in early diagnosis of Spondyloarthritis. A study of 133 patients.

OBJECTIVES: To analyse the predictive values of inflammatory back pain (IBP), positive HLA B27 antigen, increased C-reactive protein (CRP), Spondyloarthritis (SpA) features, familial history (FH), magnetic resonance sacroiliac joints (MRI-SIJ) imaging and its weight in early SpA diagnosis. METHODS: 133 patients with back pain, aged <50, duration of the pain <2 years were included. Data such as IBP, HLA B27, increased CRP, SpA features, FH, SIJ´s radiography and MRI were collected for each patient. STIR sequences were classified as strongly positive bone morrow oedema (SPBME ≥2), clearly present and easily recognisable as positive according to the ASAS criterion, weakly positive (WPBME ≥2), suggestive, but not easily recognisable and, clearly negative none of those features. T1-weighted sequences were assessed as positive/negative for erosion, fat metaplasia, backfill and sclerosis, if ≥1, for each lesion was present. MRI images were read by three blinded readers. RESULTS: The average age was 38.9 years. 47 (35.3%) patients received SpA diagnosis according to the clinical opinion. IBP was highly specific, 0.81 and sensitive, 0.83. HLA B27 was positive in a half of the SpA patients. SPBME ≥2 provided a great specificity, 0.94 and an acceptable sensitivity, 0.79. Erosion was significantly more frequent in SpA patients (72% vs 7%), specificity 0.93. The addition of erosion ≥1 to the WPBME ≥2 noticeably improved specificity, 0.98, although slightly decreased sensitivity, 0.64. Fat metaplasia and backfill were highly specific, but poorly sensitive. Factors forecasting positive diagnosis were IBP, followed by SpA features and increased CRP. CONCLUSIONS: At the onset, IBP might be a good marker for selecting patients with suspicion of SpA. The addition of erosion to the ASAS criterion might be helpful for early diagnosis, especially in patients with doubtful STIR imaging where BME is present but it is hard to determinate whether the ASAS "highly suggestive" criterion is met.

Membranous nephropathy and thymoma in a patient with ankylosing spondylitis: A case report.

RATIONALE: We report a rare case with ankylosing spondylitis (AS), thymoma, and membranous glomerulonephritis. The pathogenic mechanisms of these 3 diseases may be associated with each other. Here, we discuss the course of diagnosis and treatment. PATIENT CONCERNS: A 64-year-old woman with bilateral pain of the sacroiliac joints for 10 years and anasarca for 10 days. DIAGNOSES: A diagnosis of AS by HLA-B27 and pelvic X-ray tests, thymoma based on computed tomography and pathological diagnosis, and membranous glomerulonephritis based on renal biopsy. INTERVENTIONS: We administered methylprednisolone 500 mg/d for 3 consecutive days, followed by methylprednisolone 40 mg oral QD, for a month. OUTCOMES: The patient was followed up once a month. In the sixth month, the patient's serum creatinine had decreased to 0.96 mg/dL, urine microalbumin/creatinine decreased to 173.3 mg/g, and albumin had risen to 33.1 g/L. Pain and morning stiffness were relieved, and the Bath Ankylosing Spondylitis Disease Activity Index score dropped to 4.0. LESSONS: Although the causal relationship between AS, thymoma, and membranous nephropathy in this patient still needs to be established, the pathogenesis between the 3 diseases may have some association. In clinical practice, patients with AS need to be screened for tumors and renal complications.

Diffuse Idiopathic Skeletal Hyperostosis in a Patient With Shoulder Pain.

A 74-year-old man was referred to physical therapy by his primary care physician for insidious onset of right shoulder pain. Following examination, spinal radiographs and the human leukocyte antigen (HLA-B27) test, which is used to identify common autoimmune disorders, were completed. The radiographs revealed multilevel changes consistent with diffuse idiopathic skeletal hyperostosis, and the HLA-B27 test was positive. J Orthop Sports Phys Ther 2020;50(4):215. doi:10.2519/jospt.2020.9243.

[The clinical significance of serum autoantibodies and HLA-B(27) molecule testing in Uygur patients with human immunodeficiency virus infection].

Objective: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B(27)) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Method: A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B(27) molecule were tested. Result: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4(+)T cell count was (520±271) cells/µl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P<0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P=0.049). There were no correlations between ANA and duration of HAART, CD4(+)T cell counts and virus load (r values 0.061, 0.047, 0.121, respectively. P>0.05). Only one female patient was HLA-B(27) positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion: Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It's noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019.

Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Neuromyelitis optica spectrum disorder coexisting with ankylosing spondylitis: A case report.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, demyelinating, inflammatory disease associated with aquaporin-4 (AQP4) antibody in the central nervous system. Ankylosing spondylitis (AS), which is closely associated with leukocyte antigen B27 (HLA-B27), is a chronic inflammatory disease that primarily affects the axial skeleton. We describe the case of a 46-year-old Chinese female, with one-year history of optic neuritis, was admitted to our hospital with a complaint of bilateral lower limbs and perineum numbness for one month. AQP4-IgG antibodies were positive in both the serum and cerebrospinal fluid of the patient. Additionally, HLA-B27 was positive in the serum. Contrast-enhanced computed tomography scan revealed bilateral sacroiliitis. Magnetic resonance imaging of the spinal cord showed T2 hyperintense lesions in conus medullaris, C8-T1 and T11 of spinal cord. The patient's symptom improved after twice methylprednisolone and mycophenolate mofetil treatment. To our best knowledge, this is the first reported case of concomitant AQP4-positive NMOSD and HLA-B27-positive AS. Systematic studies on the association of NMOSD and AS are needed to clarify whether this coincidence is just a casual phenomenon or whether it points to a yet undiscovered link.

What is axial spondyloarthritis? A latent class and transition analysis in the SPACE and DESIR cohorts.

OBJECTIVES: To gain expert-judgement-free insight into the Gestalt of axial spondyloarthritis (axSpA), by investigating its 'latent constructs' and to test how well these latent constructs fit the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHODS: Two independent cohorts of patients with early onset chronic back pain (SPondyloArthritis Caught Early (SPACE)) or inflammatory back pain (IBP) (DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR)) were analysed. Latent class analysis (LCA) was used to estimate the (unobserved) potential classes underlying axSpA. The best LCA model groups patients into clinically meaningful classes with best fit. Each class was labelled based on most prominent features. Percentage fulfilment of ASAS axSpA, peripheral SpA (pSpA) (ignoring IBP) or both classification criteria was calculated. Five-year data from DESIR were used to perform latent transition analysis (LTA) to examine if patients change classes over time. RESULTS: SPACE (n=465) yielded four discernible classes: 'axial' with highest likelihood of abnormal imaging and HLA-B27 positivity; 'IBP+peripheral' with 100% IBP and dominant peripheral symptoms; 'at risk' with positive family history and HLA-B27 and 'no SpA' with low likelihood for each SpA feature. LCA in DESIR (n=576) yielded similar classes, except for the 'no-SpA'. The ASAS axSpA criteria captured almost all (SPACE: 98%; DESIR: 93%) 'axial' patients, but the 'IBP+peripheral' class was only captured well by combining the axSpA and pSpA criteria (SPACE: 78%; DESIR: 89%). Only 4% of 'no SpA' patients fulfilled the axSpA criteria in SPACE. LTA suggested that 5-year transitions across classes were unlikely (11%). CONCLUSION: The Gestalt of axSpA comprises three discernible entities, only appropriately captured by combining the ASAS axSpA and pSpA classification criteria. It is questionable whether some patients with 'axSpA at risk' will ever develop axSpA.

Associations of lymphotoxin-a (LTA) rs909253 A/G gene polymorphism, plasma level and risk of ankylosing spondylitis in a Chinese Han population.

Lymphotoxin-a (LTA) may be associated with the pathogenesis of inflammatory diseases. To assess the association of the LTA rs909253 A/G polymorphism with plasma level and risk of ankylosing spondylitis (AS) in a Chinese Han population. Genotyping and LTA plasma were tested by mass spectroscopy and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the average plasma level of LTA in AS was significantly lower than in the controls (P = 0.000). Our results also indicated that LTA rs909253 A/G was associated with a decreased risk of AS (G vs. A: P = 0.014). Significant differences were also found between the rs909253 A/G genotype and down-regulated plasma level in AS patients, compared with controls. After stratification analysis, a decreased risk of AS was associated with the LTA rs909253 G allele (G vs. A) among female patients, younger patients (Yr. < 30), HLA-B27-positive patients. In addition, In conclusion, LTA rs909253 A/G genotype has a significant relationship with decreased susceptibility to AS.

Dose HLA-B5, 7, 8, 27, and 51 Antigens Associated to Behcet's disease? A Study in Southwestern Iran.

BACKGROUND: Behcet's disease is a potentially life threatening autoimmune disease with recurrent ulcers and unknown pathogenesis. Gender and human leukocyte antigen-B51 seem to have an effective role in the clinical features of the disease. OBJECTIVE: The aim of this study is to evaluate the frequency of HLA-B5, 7, 8, 27 and 51 in behçet's disease in southwestern Iranian patients who visited the rheumatology clinic and to find the association between these HLA types and the disease. METHODS: 63 patients with behcet's disease participated in this study and peripheral blood samples were collected from them. The expression of each HLA antigen was evaluated by standard lymphocytotoxicity technique. RESULTS: Compared to other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 25% and 21% of patients were positive for HLA-B5 and HLA-B51, respectively. CONCLUSIONS: HLA-B5 and HLA-B51 are dominant positive HLA antigens among behcet's disease patients in the southwest of Iran; however, we cannot conclude that these antigens are valuable diagnostic or prognostic biomarkers due to our study limitations. We suggest studying the association between HLA-B antigens and inflammation severity in patients to determine the possible prognostic value of HLA-B antigens in Iranian population in the southwest and this region needs more studies in HLA subject among BD patients because of the frequency of BD to evaluate the value of HLA typing in BD prognosis.

Prevalence of Juvenile Idiopathic Arthritis in the Alaska Native Population.

OBJECTIVE: To determine the prevalence and clinical characteristics of juvenile idiopathic arthritis (JIA) in Alaska Native children. METHODS: Potential cases of JIA were identified by querying administrative data from hospitals and clinics in the Alaska Tribal Health System for codes possibly identifying JIA. Medical record abstraction was performed to confirm criteria met for JIA, demographic and clinical characteristics, and treatment patterns. Individuals age ≤18 years with a confirmed diagnosis of JIA were included. The denominator for prevalence was the 2015 Alaska Area Indian Health Service user population age of ≤18 years. RESULTS: The unadjusted prevalence of JIA in Alaska Native children was 74.6 per 100,000 (age-adjusted 79.0 per 100,000). JIA was more common in females than males (unadjusted prevalence 105.8 versus 45.0 per 100,000). Oligoarthritis was the most common subtype (31% of cases), but polyarthritis and enthesitis-related arthritis were also common (26% and 24% of cases, respectively), with a notably high prevalence of enthesitis-related arthritis. The median age at diagnosis was 9 years. Of the combined cohort with results available, 56% were antinuclear antibody positive, 23% were rheumatoid factor positive, 19% were anti-cyclic citrullinated peptide antibody positive, and 57% had the presence of HLA-B27. Uveitis had been diagnosed in 16% of cases. CONCLUSION: The prevalence of JIA in Alaska Native children may be higher than the general US population. Enthesitis-related arthritis makes up a higher proportion of cases than in other populations described likely because of the high prevalence of HLA-B27 in this population.

Differences between females and males in axial spondyloarthritis: data from a real-life cross-sectional cohort.

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory joint disease that usually presents with axial symptoms, but can also present with peripheral and extra-articular manifestations. It occurs equally in females and males. The diagnostic delay for axSpA is 5-7 years, and is significantly longer in females than in males. The aim of this study is to investigate the difference in disease characteristics between females and males with axSpA and to stratify this difference according to human leucocyte antigen (HLA)-B27 status.Method: Clinical characteristics, spondyloarthritis (SpA) features, disease activity parameters, X-rays of sacroiliac joints, and laboratory results were assessed in a real-life cross-sectional cohort of 389 patients with a clinical diagnosis of axial or peripheral SpA, and compared between genders.Results: Of 389 patients included, 313 had a clinical diagnosis of axSpA [females vs males, 131 (42%) vs 182 (58%), respectively]. Females had less radiographic axSpA according to the modified New York criteria (38.9% vs 63.7%, respectively), had a higher erythrocyte sedimentation rate [(median (interquartile range) 11 (5-23) vs 8 (3-16) mm/h), and reported higher disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (mean ± sd 5.2 ± 2.1 vs 4.6 ± 2.2). No differences were found in clinical characteristics or SpA features, or when stratifying for HLA-B27 status.Conclusions: In this real-life cohort of patients with axSpA, although males more often had structural damage on X-rays, females had similar disease with regard to SpA features and at least equal disease activity parameters compared to males.

Comparison of secondary IgA nephropathy in patients with ankylosing spondylitis and rheumatoid arthritis.

Objectives: The aim of the present study was to investigate the differences in clinic-pathological features of secondary IgA nephropathy (SIgAN) between patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA).Methods: Forty-six patients with SIgAN related to AS (SIgAN-AS) and 26 patients with SIgAN related to RA (SIgAN-RA) were enrolled in this retrospective study. The two groups were compared for their clinic-pathological characteristics.Results: The 10-year prevalence of SIgAN-AS and SIgAN-RA were 167 per 1000 and 51.3 per 1000, respectively. Compared with SIgAN-RA patients, SIgAN-AS patients had lower incidences of edema and nephrotic syndrome, but higher levels of eGFR, serum C3, and CD3- and CD8-positive T-cell counts, but less incidences of acute tubulointerstitial lesions and interlobular arterial lesions. IgM was the most familiar co-depositing immune complex on tissue with significantly different frequencies. In SIgAN-AS patients, those with positive HLA-B27 presented with lower levels of proteinuria, higher levels of serum IgG and C3, and less incidence of renal insufficiency, crescents >14.5%, glomerular sclerosis >32.6% and segmental sclerosis >5.2%.Conclusion: SIgAN was more prevalent in AS than in RA. SIgAN-AS patients differed from SIgAN-RA patients in certain clinic-pathological characteristics. HLA-B27 likely protected SIgAN-AS patients from renal insufficiency.