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.

Significant association of HLA-A26 with uveitis and gastrointestinal involvement in patients with Behçet's disease in a multicenter study.

OBJECTIVES: Specific HLA haplotypes are associated with Behçet's disease (BD). Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in BD have not been well demonstrated, we aimed to examine them. METHODS: This multicenter, cross-sectional, observational study enrolled patients with BD who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score. RESULTS: Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harboring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (p = 0.03) and coexistence of uveitis and gastrointestinal involvement (p = 0.002), and higher Krause scores (p = 0.02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (p = 0.001) and gastrointestinal involvement in patients with uveitis (p = 0.001). CONCLUSIONS: Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.

Neuro-Behçet's Disease Onset in the Context of Tuberculous Meningoencephalitis: A Case Report.

Behçet's disease (BD) is a systemic vasculitis that frequently presents with a relapsing-remitting pattern. CNS involvement (Neuro-Behçet) is rare, affecting approximately 10% of patients. Its etiological mechanisms are not yet fully understood. The most commonly accepted hypothesis is that of a systemic inflammatory reaction triggered by an infectious agent or by an autoantigen, such as heat shock protein, in genetically predisposed individuals. Mycobacterium tuberculosis is known to be closely interconnected with BD, both affecting cell-mediated immunity to a certain extent and probably sharing a common genetic background. We present the case of a 34-year-old Caucasian woman who had been diagnosed with tuberculous meningitis 15 months prior, with significant neurological deficits and lesional burden on MRI with repeated relapses whenever treatment withdrawal was attempted. These relapses were initially considered as reactivation of tuberculous meningoencephalitis, and symptoms improved after a combination of antituberculous treatment and corticosteroid therapy. After the second relapse, the diagnosis was reconsidered, as new information emerged about oral and genital aphthous lesions, making us suspect a BD diagnosis. HLA B51 testing was positive, antituberculous treatment was stopped, and the patient was started on high doses of oral Cortisone and Azathioprine. Consequently, the evolution was favorable, with no further relapses and slow improvements in neurological deficits. To our knowledge, this is the first report of Neuro-Behçet's disease onset precipitated by tuberculous meningitis. We include a review of the available literature on this subject. Our case reinforces the fact that Mycobacterium tuberculosis infection can precipitate BD in genetically predisposed patients, and we recommend HLA B51 screening in patients with prolonged or relapsing meningoencephalitis, even if an infectious agent is apparently involved.

A Changed Man: A Rare Case of Behcet's Disease Autoimmune Encephalitis.

Behcet's disease (BD) is characterized by recurrent oral ulcers with concomitant systemic multi-organ involvement, which may include neurological disease, ocular disease, vascular disease, genital ulcers, skin lesions, and arthritis. The clinical symptoms arise from vasculitis that involves small, medium, and large blood vessels. We present the case of a young male who presented with atypical Behcet's autoimmune encephalitis with recurrent oral ulcers, neurological manifestations, HLA-B51 positivity, abnormal EEG findings, and improvement following multiple plasma exchange treatments.

Severe Occlusive Retinal Vasculitis in an Immunocompetent Patient with Chronic CMV Anterior Uveitis.

PURPOSE: We report a unique case of non-necrotizing occlusive retinal vasculitis presenting two years following chronic hypertensive uveitis. METHODS: Case Report. RESULTS: A 32-year-old Iraqi woman with a history of Posner-Schlossman Syndrome diagnosed 10 years prior presented with blurred vision and redness in her left eye. Examination demonstrated ocular hypertension, keratic precipitates, and inflammatory cells in the anterior chamber. Quantitative real-time PCR confirmed the presence of cytomegalovirus in the aqueous humor, and dilated posterior segment examination was negative for any signs of intraocular inflammation, retinitis, or vasculitis. Her uveitis workup was otherwise negative, and she was treated with valganciclovir for 6 months. Two years after her initial presentation, she was noted to have a new vitreous hemorrhage in the left eye. Fluorescein angiography demonstrated an occlusive retinal vasculitis with extensive neovascularization without retinitis. Quantitative real-time PCR again demonstrated the presence of cytomegalovirus in the anterior chamber. Her uveitis workup was repeated, which has now returned positive for HLA-B51. She otherwise did not demonstrate any systemic signs of Behcet's Disease. She was restarted on valganciclovir and oral prednisone and referred to rheumatology for consideration of adalimumab initiation. Thus far she has responded very well to treatment. CONCLUSION: This case highlights the importance of serial posterior segment examinations and HLA-B51 testing in individuals with cytomegalovirus anterior uveitis.

The novel HLA-B*51:389 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*51:389 differs from HLA-B*51:02:01:01 by one nucleotide in exon 2.

HLA-B*51:197: A composite product of interlocus recombination of B*51:01:01:01 and C*01:02:01:01.

The HLA-B*51:197 allele is generated from the interlocus recombination of both HLA-B*51:01:01:01 and HLA-C*01:02:01:01 alleles.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Next generation sequencing identifies two novel HLA alleles, HLA-B*51:395 and HLA-DQB1*06:478.

We identified two novel HLA alleles by NGS, HLA-B*51:395 and HLA-DQB1*06:478.

Characterization of the novel HLA-B*51:394Q allele by sequencing-based typing.

HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.

Identification of the novel HLA-B*51:413 allele by next-generation sequencing in a Chinese Han individual.

The novel allele HLA-B*51:413 differs from HLA-B*51:92:02 by one nucleotide substitution in exon 3.

Case report: Deep vein thrombosis as the sole clinical feature of Behcet's syndrome.

Introduction: Behcet's syndrome is a rare, chronic, systemic condition often categorized within the group of vasculitides. It presents a diagnostic challenge due to its varied clinical manifestations and the absence of a definitive laboratory test. Its etiology remains unclear but may involve genetic, infectious, and environmental factors. Case presentation: We report the case of a 16-year-old male who presented with deep vein thrombosis, followed by recurrent episodes of breakthrough thrombosis, despite adequate anticoagulant therapy. The patient did not meet the International Study Group (ISG) criteria nor the International Criteria for Behcet's syndrome (ICBD) due to the absence of characteristic features such as oral aphthous ulcers, genital ulcers, and uveitis. Later in the disease course, after ruling out other causes of breakthrough thrombosis, he tested positive for HLA-B51, an allele associated with Behcet's syndrome, and exhibited a pathergy reaction. Discussion: The patient's clinical course underlines the diagnostic complexity associated with Behcet's syndrome and highlights the importance of maintaining a broad differential diagnosis in cases of recurrent thrombosis. Although HLA-B51 testing is not routinely recommended, it played a pivotal role in our case, underscoring the value of an integrated diagnostic approach. Furthermore, this case reinforces the potential for atypical presentations of Behcet's syndrome, necessitating vigilant clinical awareness. After establishing the diagnosis, we successfully treated the patient with immunosuppressive therapy, significantly improving his condition.

Acometimento vascular na doença de Behçet: o processo imunopatológico / Vascular involvement in Behçet's disease: the immunopathological process

Resumo A doença de Behçet constitui uma forma rara de vasculite sistêmica, que acomete de pequenos a grandes vasos. É caracterizada por manifestações mucocutâneas, pulmonares, cardiovasculares, gastrointestinais e neurológicas. Sua apresentação clínica é bastante ampla, variando de casos mais brandos a casos graves, com acometimento multissistêmico, caracteristicamente com exacerbações e remissões. Suas causas ainda são desconhecidas; entretanto, há evidências genéticas, ambientais e imunológicas, como a associação com o alelo HLA-B51. Todas essas, em conjunto, apontam para um processo imunopatológico anormal, com ativação de células da imunidade inata e adaptativa, como as células natural killer, neutrófilos e células T, que geram padrões de respostas e citocinas específicos capazes de gerar mediadores que podem lesionar e inflamar o sistema vascular, resultando em oclusões venosas, arteriais e/ou formação de aneurismas.

Abstract Behçet's disease is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Its clinical presentation is quite wide, ranging from milder cases to severe cases, with multisystemic involvement, characteristically with exacerbations and remissions. Its etiopathogenesis is still unclear, although there is evidence of genetic, environmental, and immunological factors, such as the association with the HLA-B51 allele. In conjunction, all of these point to an abnormal immunopathological process, with activation of cells of innate and adaptive immunity, such as NK cells, neutrophils, and T cells, which generate specific response patterns and cytokines capable of generating mediators that can damage and inflame blood vessels, resulting in venous and arterial occlusions and/or aneurysm formation.