Antigen B27 Research Articles

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

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

Design a novel of Brucellosis preventive vaccine based on IgV_CTLA-4 and multiple epitopes via immunoinformatics approach

Brucellosis is a zoonotic disease caused by Brucella, which is difficult to eliminate by conventional drugs. Therefore, a novel multi-epitope vaccine (MEV) was designed to prevent human Brucella infection. Based on the method of “reverse vaccinology”, cytotoxic T lymphocyte epitopes (CTLEs), helper T lymphocyte epitopes (HTLEs), linear B-cell epitopes (LBEs) and conformational B-cell epitopes (CBEs) of four Brucella proteins (VirB9, VirB10, Omp 19 and Omp 25) were obtained. In order to keep the correct protein folding, the multiple epitopes was constructed by connecting epitopes through linkers. In view of the significant connection between human leukocyte antigen CTLA-4 and B7 molecules found on antigen presenting cells (APCs), a new vaccine (V_C4MEV) for preventing brucellosis was created by combining CTLA-4 immunoglobulin variable region (IgV_CTLA-4) with MEV protein. Immunoinformatics analysis showed that V_C4MEV has a good secondary and tertiary structure. Additionally, molecular docking and molecular dynamics simulation (MD) revealed a robust binding affinity between IgV_ CTLA-4 and the B7 molecule. Notably, the vaccine V_C4MEV was demonstrated favorable immunogenicity and antigenicity in both in vitro and in vivo experiments. V_C4MEV had the potential to activate defensive cells and immune responses, offering a hopeful approach for developing vaccines against Brucella in the upcoming years.

Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice.

Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization.

Chinese medicine compound prescription HeQi San ameliorates chronic inflammatory states and modulates gut flora in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model

BackgroundPolycystic ovary syndrome (PCOS) is a common and complex endocrine disease in women, with a prevalence of 5% to 18% worldwide. HeQi San (HQS) is a Chinese medicine compound prescription, which has been applied to treat various endocrine and metabolic diseases. ObjectiveThe study was intended to investigate the effect of HQS on PCOS, and clarify the potential mechanism via in vivo and in vitro experiments. MethodsThe PCOS mouse model was established by injecting the dehydroepiandrosterone (DHEA) subcutaneously and fading high-fat diet for 3 weeks. After making model, PCOS mice were treated with HQS (8.75 g/kg and 17.5 g/kg, ig.) for 4 weeks. Firstly, we assessed the histopathological changes in ovary tissues and detected the hormone level. Subsequently, the study evaluated the capability of anti-inflammatory and regulating macrophage polarization of HQS in vivo and in vitro. The secretion of inflammation indicators was measured with Elisa kits, and the expression level of phosphorylated nuclear factor kappa-B (P-NFκB) and B-lymphocyte activation antigen B7 (CD80) was measured by immunofluorescence and Western blot. Meanwhile, the apoptosis of ovarian granulosa cells was detected via tunel staining and Western blot. The co-culture model in vitro was utilized to assess the effect between macrophage polarization and human ovarian granulosa cells (KGN cells) apoptosis. Furthermore, 16S rDNA sequencing was utilized to elevate gut microbiota change in PCOS mice. ResultsHQS reversed the abnormal hormone increase, ameliorated insulin resistance, and improved histopathological changes of the ovary tissue to exert the therapeutic effect. HQS inhibited the expression of P-NF-κB and decreased the production of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) to further prohibit the macrophage M1 polarization in ovary tissues and macrophages. The apoptosis-positive cells, Bcl-2 Assaciated X protein (BAX), and cleaved-caspase 3 expression were also decreased in the treatment group. The B-cell lymphoma-2 (Bcl2) expression was enhanced after HQS treatment in vivo. The co-culture experiments also verified that HQS could prevent the apoptosis of KGN cells. Furthermore, HQS mediated the abundance of gut flora. The abundance of bifldobacterium and parasutterella was increased and the abundance of lachnoclostridium was decreased. ConclusionThe study verified that HQS has the effect of anti-inflammation and inhibits macrophage M1 polarization. Besides, HQS could mediate the abundance of gut microbiota in mice with PCOS. Thus, this study would provide more reasonable basis of HQS for clinical use. In conclusion, HQS might be a potential candidate for PCOS treatment.

Peculiarities of HLA b27 antigen detection in patients with ankylosing spondylitis

Peculiarities of HLA b27 antigen detection in patients with ankylosing spondylitis

A Quadrivalent mRNA Immunization Elicits Potent Immune Responses against Multiple Orthopoxviral Antigens and Neutralization of Monkeypox Virus in Rodent Models.

The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.

The Frequency of HLA-B27 Antigen Positivity in Patients with Rheumatoid Arthritis and Anklylosing Spondylitis and The Relationship Between HLA-B27 Antigen and Other Autoantibodies

Aims: The aim of this study is to retrospectively demonstrate frequency of Human Leukocyte Antigen (HLA)-B27 antigen positivity and relationship between HLA-B27 positivity and other autoantibodies and between HLA-B27 positivity and treatment in patients diagnosed with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and methods: The study is a retrospective study. Patients who were diagnosed with RA and AS as a result of the examinations performed at Physical Medicine and Rehabilitation polyclinic between January 2017 and September 2022 were retrospectively screened, and patients whose HLA-B27 antigen was tested were included in study. Results: A total of 569 patients, 199 with RA and 370 with AS were included in study. While HLA-B27 was positive in 11% of patients with RA, it was 37.5% in patients with AS and there was a significant difference between the groups. When we analyzed the correlation of autoantibodies with HLA-B27, we found that HLA-B27 was not correlated with RF, ANTI-CCP or ANA. When we analyzed the relationship between HLA-B27 and the treatment method, there was no significant relationship between HLA-B27 and treatment method. Conclusion: While HLA-B27 was found to be 5% positive in the general population in the literature, we found 11% in 199 patients with RA. This study is important because it shows that HLA-B27 positivity is not very common in patients diagnosed with AS recently contrary to popular belief. More studies are needed to evaluate HLA-B27 frequency in RA and AS

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

BackgroundTo 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.MethodsWe 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.ResultsWe 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).ConclusionAlmost 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.

Examination of the cross-reactivity between vaccinia virus Tiantan strain and monkeypox virus

AimTo investigate the cross-reactivity between the sera collected from Vaccinia Virus Tiantan Strain vaccinated rabbits and viral antigens of monkeypox virus. MethodsVaccinia viruses were prepared on chicken embryo fibroblasts (CEF) and Vero cells respectively named as CEF-VTT NVSI-1 and Vero-VTT NVSI-1. Rabbits were inoculated with a total of three doses of adjuvanted 1.3 × 108 PFU CEF-VTT NVSI-1 each dose or adjuvanted 3.9 × 107 PFU Vero-VTT NVSI-1 (Freunds complete adjuvant) via the subcutaneous route. We then performed the enzyme-linked immunosorbent assay (ELISA) and bio-layer interferometry (BLI) for determination of the binding activity and affinity of immune sera to five crucial surface antigens on monkeypox virus including A35, B6R, H3 and to corresponding homologous antigens A33R, B5 and L1R of vaccinia virus. For comparison, plaque reduction neutralizing tests were used to evaluate the neutralization of immune sera against vaccinia virus. ResultsBoth CEF-VTT NVSI-1 and Vero-VTT NVSI-1 vaccinations following planned schedule could induce neutralizing antibody titers greater than 1:2048 in rabbit sera. Binding antibodies targeting monkeypox viral antigens were confirmed by both indirect ELISA and BLI methods. Indirect ELISA for rabbit sera revealed 1:51200 binding antibody titers to A35/B6R/H3 monkeypox virus antigens while BLI tests yielded affinities at 2 × 10−6 to 8 × 10−7 between the sera and the three antigens. Similarly, such sera showed binding strength to vaccinia virus antigens A33R/B5/L1R consistent with that to three preceding monkeypox virus antigens. These results demonstrated the cross-reactivity between the sera of vaccinia virus vaccinated animals and monkeypox virus antigens. Traditional ELISA test and BLI method displayed a high consistency in antigen screening and they were further proved to correlate to the results of plaque reduction neutralizing test, which indicates that BLI could be utilized as an indirect alternative for assessment of neutralizing activity of samples in response to live virus. ConclusionsSera of vaccinia virus-vaccinated rabbits exhibited cross-reactivity with viral antigens of monkeypox virus. Potential in improving the accuracy of antigen discovery while reducing the lengthy work needed for the screening as BLI method possesses, it contributes greatly to the rapid preliminary evaluation of immune response generated by vaccines.

Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara–Bavaria Nordic vaccine against mpox in children: a national outbreak response

In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children. This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. UK Health Security Agency.

Reduced susceptibility to COVID-19 associated with ABO blood group and pre-existing anti-A and anti-B antibodies

BackgroundSusceptibility to severe acute respiratory syndrome coronavirus 2 shows individual variability in un-vaccinated and previously un-exposed individuals. We investigated the impact of ABO blood group, titers of anti-A and anti-B, other blood group antigens, and the extracellular deposition of ABH antigens as controlled by secretor fucosyltransferase 2 (FUT2) status. Study design and methodsWe studied incidents in three different hospitals between April to September 2020, where un-diagnosed coronavirus disease 2019 (COVID-19) patients were cared for by health care workers without use of personal protection and with close contact while delivering therapy. We recruited 108 exposed staff, of whom 34 were diagnosed with COVID-19. ABO blood type, titer of anti-A and -B, blood group specific alleles, and secretor status were determined. ResultsBlood group O was associated with lower risk of COVID-19 (OR 0.39, 95 %CI (0.16–0.92), p = 0.03) compared to non-O, i.e., blood groups A, B and AB. High titer anti-A immunoglobulin G (IgG) compared to low titer was associated with lower risk of COVID-19 (OR 0.24 95 %CI (0.07–0.78), p = 0.017). High titer of anti-B immunoglobulin M (IgM) compared to no anti-B (IgM) was associated with lower risk of COVID-19 (OR 0.16, 95 %CI (0.039–0.608), p = 0.006) and the same applies to low titer anti-B (IgM) compared to no titer (OR 0.23, 95 %CI (0.07–0.72), p = 0.012).The 33Pro variant in Integrin beta-3, that is part of human platelet antigen 1b (HPA-1b), was associated with lower risk of COVID-19 (OR 0.23, 95 %CI (0.034–0.86), p = 0.028). ConclusionOur data showed that blood group O, anti-A (IgG) titer, anti-B (IgM) titer as well as HPA-1b are associated with lower risk for COVID-19.

Development of an enzyme linked immunosorbent assay using recombinant cathepsin B5 antigen for sero-surveillance of bovine tropical fasciolosis

Bovine tropical fasciolosis, caused by Fasciola gigantica, is a major parasitic disease in tropical countries responsible for significant production losses in animal husbandry practices. The disease is transmitted by the Radix sp. snails. In the early developmental stage of the parasite, the juveniles and immature flukes cause considerable damage to the liver parenchyma of the bovine host while migrating through the liver. The cathepsin (cat) B5 is a cysteine protease that is present in the excretory-secretory product of the fluke both in immature and adult stages. The early detection of fasciolosis is very critical in effective disease management. In this study, the cathepsin B5 gene from newly excysted juveniles were cloned, sequenced and analyzed. The phylogenetic analysis revealed existence of two distinct clades. The clade I includes cat B 1 to B3 whereas clade II consist of cat B4 to B7. Further, the present study was aimed to develop an enzyme linked immuno sorbent assay (ELISA) using recombinant cat B5 antigen. The developed enzyme immuno assay showed 95.3 % sensitivity and 92.4 % specificity with a cut-off of 60 % percent positive. It revealed weighted Kappa value as 0.768 (95 % CI 0.648–0.889) when compared with ELISA using native cathepsin protein. Hence, the developed assay can be exploited as a potent tool in the diagnosis and sero-surveillance of bovine tropical fasciolosis.

58 Comparison of the 2015 pediatric diagnostic criteria for Behcet’s disease with the 2014 and 1990 International Study Group Diagnostic Criteria

BackgroundBehçet's disease is a multisystem vasculitis whose pathogenesis remains unclear. Although usually described in young adults, it may begin in childhood. The diagnosis is clinical, based on international criteria. The limitations of early diagnosis are related to the progressive onset of symptoms and the variety of differential diagnoses at this age in the absence of a pathognomonic diagnostic test.ObjectivesTo report the epidemiological features of our series and to compare the 2015 pediatric criteria with the 2014 and 1990 international criteria.Materials and MethodsThis is a monocentric, retrospective study of 31 children over an 11-year period from January 2011 to December 2021. All patients suspected with Behcet's disease by a pediatric rheumatologist were included in the study, the 2014 international criteria “ISG 2014” being the gold standard classification criteria used in our center.Results31 cases of Behcet's were collected. The mean age was 10 years (5.5–16) ± 2.87 years. A female predominance is noted with a sex ratio F/M of 1.21. A quarter of the patients were from a consanguineous marriage and 38.7% had a family history of Behcet disease. Mucocutaneous manifestations were represented by recurrent oral aphthosis 87.1%, genital aphthosis 29%, pseudofolliculitis 48.4%, erythema nodosum 6.5% and acne lesions 3.2%. The pathergy test was positive in 1 case. Ocular involvement was reported in 29% and joint involvement in 45.2%. Thromboembolic complication was seen in 9.6% and neurobehcet in one patient. The HLA B51 antigen was present in 45.2% of cases. In our series 38.7% respond the pediatric criteria, while 61.3% met the 2014 international criteria and 35.5% met the 1990 international criteria. The 2015 pediatric criteria have respectively a sensitivity and specificity of 63.2% and 100% (p = 0.002) compared with the 2014 international criteria taken as gold standard, as well as the 1990 international criteria with a respective sensitivity and specificity of 52.6% and 91.7% (p = 0.034).ConclusionOur study highlights a female predominance, a high rate of consanguinity and familial Behcet. The sensitivity and specificity of the 1990 pediatric and international criteria appear to be better than those of 2014, with a more significant trend for the 2015 pediatric criteria (p = 0.002).

Association of HLA-B27 antigen with clinical and laboratory parameters in patients with juvenile idiopathic arthritis.

Aim To analyse the association of human leukocyte antigen B27 with clinical and laboratory parameters in patients with juvenile idiopathic arthritis (JIA) at the disease onset. Methods A retrospective review of medical records of 25 HLAB27 positive and 25 HLA-B27 negative JIA patients was performed. The diagnosis of JIA was based on the 1997-2001 International League Against Rheumatism (ILAR) criteria. Collected data: age, sex, HLA- B27 antigen presence, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid-factor (RF), antinuclear antibody (ANA), fever, rash, uveitis, enthesitis, inflamed joints and subtype of JIA. Results HLA- B27 positive study group had more boys (p=0.01), higher erythrocyte sedimentation rate (p=0.038), higher presence of fever (p= 0.025) and enthesitis (p=0.024). Any significant difference in age of the disease onset, CRP, ANA, RF, rash, uveitis, inflamed joint and dactylitis was not noticed. The most common subtype of JIA in the HLA-B27 positive patients was ERA (60%). Conclusion This study showed that the presence of HLA- B27 antigen plays a significant role in determining the presenting clinical and laboratory characteristics in JIA patients.

Antigen-guided depletion of anti-HLA antibody–producing cells by HLA-Fc fusion proteins

AbstractPlatelet transfusion and transplantation of allogeneic stem cells and solid organs are life-saving therapies. Unwanted alloantibodies to nonself human leukocyte antigens (HLAs) on donor cells increase the immunological barrier to these therapies and are important causes of platelet transfusion refractoriness and graft rejection. Although the specificities of anti-HLA antibodies can be determined at the allelic level, traditional treatments for antibody-mediated rejection nonselectively suppress humoral immunity and are not universally successful. We designed HLA-Fc fusion proteins with a bivalent targeting module derived from extracellular domains of HLA and an Fc effector module from mouse IgG2a. We found that HLA-Fc with A2 (A2Fc) and B7 (B7Fc) antigens lowered HLA-A2− and HLA-B7−specific reactivities, respectively, in sera from HLA-sensitized patients. A2Fc and B7Fc bound to B-cell hybridomas bearing surface immunoglobulins with cognate specificities and triggered antigen-specific and Fc-dependent cytotoxicity in vitro. In immunodeficient mice carrying HLA-A2–specific hybridoma cells, A2Fc treatment lowered circulating anti−HLA-A2 levels, abolished the outgrowth of hybridoma cells, and prolonged survival compared with control groups. In an in vivo anti-HLA-A2−mediated platelet transfusion refractoriness model, A2Fc treatment mitigated refractoriness. These results support HLA-Fc being a novel strategy for antigen-specific humoral suppression to improve transfusion and transplantation outcomes. With the long-term goal of targeting HLA-specific memory B cells for desensitization, further studies of HLA-Fc’s efficacy in immune-competent animal models are warranted.

ОЦЕНКА ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ПРИМЕНЕНИЯ ЭТАНЕРЦЕПТА У ПАЦИЕНТОВ С НЕСИСТЕМНЫМИ ВАРИАНТАМИ ЮВЕНИЛЬНОГО АРТРИТА: 10-ЛЕТНИЙ ОПЫТ ПРИМЕНЕНИЯ В УСЛОВИЯХ ФЕДЕРАЛЬНОГО ЦЕНТРА

TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.

Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations

ABSTRACT Myxoid liposarcoma (MLPS) has different patterns that are often difficult to distinguish from other soft tissue lesions. MLPS is characterized by a reciprocal translocation involving the DNA Damage Inducible Transcript 3 gene (DDIT3) that can be detected using fluorescent in situ hybridization (FISH). Recently, the marker for cancer testis antigen 1b (CTAG1B) was found to be expressed in MLPS. The aim of the present study was to assess the potential use immunohistochemistry (IHC) for CTAG1B expression and DDIT3 rearrangement to diagnose MLPS and distinguish it from similar lesions. Out of 29 cases including MLPS and its mimics, CTAG1B was expressed in 92.86% of cases of MLPS and 20% of its mimics. DDIT3 rearrangement was 100% sensitive and 92.86% specific in distinguishing MLPS from its mimics. The DDIT3 rearrangement was found to be more sensitive but less specific than cytoplasmic expression of CTAG1B marker. DDIT3 polysomy and amplification were detected in some cases. Therefore, both CTAG1B expression and FISH for DDIT3 gene can be used to distinguish MLPS from similar tumors. The use of both immunohistochemistry for CTAG1B in addition to DDIT3 gene rearrangement detection by FISH was more specific than using either of them alone. However, the DDIT3 gene rearrangement alone was the most sensitive test for distinguishing MLPS from its mimics.

P057 Uveitis in enthesitis-related arthritis: what are the predictive factors?

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood. Uveitis is its most common extra-articular manifestation [1]. It is a potentially sight-threatening condition with a considerable risk of morbidity. This study aimed to describe the prevalence and characteristics of JIA-related uveitis in enthesitis-related arthritis (ERA) patients. Methods We conducted a retrospective study including 40 patients with JIA according to the classification criteria of the International League of Associations for Rheumatology (ILAR). All selected patients presented with ERA. A screening of uveitis was conducted in all patients. Clinical, radiologic and, biologic features of JIA were collected. We evaluated the association between these features and the presence of uveitis. Results The mean age of our patients was 24 years, with a sex ratio of 3. The mean age at the onset of JIA was 11 years. Upon screening, fifteen percent of the patients had active uveitis. Nine percent of the patients presented with an acute onset of JIA. Forty-six percent had initial spinal symptoms, while 26% presented with peripheral onset. Upon examination, 4% of the patients presented with monoarthritis, 20.4% with oligoarthritis and 34.8% with polyarthritis. Thirteen percent had enthesitis. Fifty-seven percent of the patients had coxitis. Sixty-eight percent had sacroiliitis. The mean CRP and ESR levels were respectively 16 mg/l and 34. Human leucocyte antigen (HLA) B27 screening came back positive in 11% of the cases. The mean BASDAI and BASFI levels were both at 4.7. The mean MASES was 0.44. Twenty percent of the patients received NSAIDs. Eleven percent received methotrexate, 18% salazopyrine and, 5.6% biologics. A significant association was established between the presence of uveitis and a polyarticular onset of JIA (P = 0.036). However, no significant associations were established with the sex of patients (P = 0.457), age of onset (P = 0.828), activity of the disease as evaluated by BASDAI (P = 0.40) and MASES (P = 0.87), inflammatory markers (CRP P = 0.946, and ESR P = 0.662), the use of NSAIDS (P = 1), methotrexate (P = 0.318), salazopyrine (P = 0.170) and biologics (P = 1). Conclusion In conclusion, uveitis associated with JIA is a serious and sight-threatening disease. Several factors associated with a more severe disease development have been identified [2–4]. Our study showed a significant association between the polyarticular onset of JIA and the occurrence of uveitis. Also, our study showed no significant association with male gender and HLA-B27 in children, unlike previous studies of spondyloarthritis conducted in adults [5–6]. We conclude that the screening of uveitis should be performed in all JIA patients, especially those presenting initially with polyarthritis.

Peculiarities of distribution of HLA class I antigens in patients with lihen planus

The article presents data on the distribution characteristics of the HLA class I system antigens in patients with lichen planus.
 Aim. To study the patterns of distribution of HLA class I antigens in the general group. To establish the presence of an association of the disease with antigens of the HLA class I.
 Material and methods. Laboratory analysis of the distribution of HLA class I antigens was carried out in 60 patients with various forms of lichen planus who consider themselves Russian on the basis of linguistic and ethnicity. The duration of the disease is 120 years.
 Results. When analyzing the typing results in the general group of patients; a tendency to negative association of HLA-A11 and HLA-B7.
 It was found that the frequency of haplotype combinations A1-B8; A2-B27; A2-B40; A3-B35 significantly exceeded that of healthy people. Analysis of the frequency of phenotypic combinations revealed a significant increase in A3-A19 and B12-B35.
 Conclusion. Haplotype and phenotypic combinations of HLA A1-B8; A2-B27; A2-B40; A3-B35; A3-A19; B12-B35 are provoking factors in the development of various forms of the disease. The presence of these genetic traits in the individual increases the risk of developing lichen planus by 311 times. In turn; the HLA-A11 and B7 antigens play a protective role.

The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression

Acute Myeloid Leukaemia (AML) is a neoplasia characterised by rapid proliferation and an increased rate of relapses. The AML blasts display features of antigen-presenting cells (APC), and thus can directly modulate the anti-tumour T cell responses. The bone marrow of a group consisting of 30 newly diagnosed patients and four healthy donors (HD) was investigated for the expression of HLA-DR, several molecules involved in MHC-II antigen-presentation and MHC-II groove editing, like HLA-DM, CD74 and CLIP, as well as a set of immune checkpoint ligands, like ICOS-L, B7.2, PD-L2 and B7-H3. The patients were further characterised for their genetic anomalies and distributed to favourable, intermediate and adverse ELN risk categories. We were able to show that while 23% of our patients displayed a low level of HLA-DR surface expression, all patients displayed higher HLA-DM and CD74 expression compared to HD. However, a higher CLIP expression was noticed only in the HLA-DR low patients. The co-inhibitory PD-L2 and B7-H3 molecules were increased in the cases with normal HLA-DR expression; oppositely, the co-stimulatory ICOS-L and the dual function B7.2 were significantly increased in the cases with HLA-DR low expression. Furthermore, no favourable ELN risk cases were found within the HLA-DR low group. All in all, these data show that the AML with low versus normal HLA-DR expression display different profiles of MHC class II machinery molecules and B7 ligands, which are correlated with distinct ELN stratification. Furthermore, as our study included healthy individuals, it offers valuable information about the expression levels that should be considered as normal for these markers known to cause differences in peptide repertoires, reflected further in distinct T-cells polarisation pathways.