1. Serological response after COVID-19 infection compared to vaccination against COVID-19 in children with autoimmune rheumatic diseasesTjaša Šinkovec Savšek, Mojca Zajc Avramovič, Tadej Avčin, Miša Korva, Tatjana Avšič-Županc, Nataša Toplak, 2024, original scientific article Abstract: Background Paediatric patients with autoimmune rheumatic diseases (pARD) have a dysregulated immune system, so infections present a major threat to them. To prevent severe COVID-19 infections we aimed to vaccinate them as soon as possible. Studies have shown that the BNT162b2 vaccine is safe, effective, and immunogenic, however, in a short observation period, only. Methods The main objective was to compare the serological response between three groups of pARD: after SARSCoV-2 infection, after vaccination against COVID-19 with two doses of the BNT162b2 vaccine, and after experiencing both events. Data on demographics, diagnosis, therapy, and serology (anti-SARS-CoV-2 IgG/IgA) were collected from March 2020 to April 2022. For statistical analysis ANOVA, Mann-Whitney U test, Chi-square test and Fisher’s exact test were applied. To compare adverse events (AE) after vaccination we included a control group of healthy adolescents. Results We collected data from 115 pARD; from 92 after infection and 47 after vaccination. Twenty-four were included in both groups. Serological data were available for 47 pARD after infection, 25 after vaccination, and 21 after both events. Serological response was better after vaccination and after both events compared to after infection only. No effect of medication on the antibody levels was noted. The safety profile of the vaccine was good. Systemic AE after the first dose of the vaccine were more common in healthy adolescents compared to pARD. In the observation period of 41.3 weeks, 60% of vaccinated pARD did not experience a symptomatic COVID-19 infection. Conclusions IgG and IgA anti-SARS-CoV-2 levels were higher after vaccination and after both events compared to after infection only. Six months after vaccination we observed an increase in antibody levels, suggesting that pARD had been exposed to SARS-CoV-2 but remained asymptomatic.
Keywords: covid-19, vaccination, efficacy, paediatric autoimmune rheumatic diseases
Published in DiRROS: 16.06.2026; Views: 153; Downloads: 117
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2. Ocular manifestations in juvenile Behçet’s disease : a registry-based analysis from the AIDA networkCarla Gaggiano, Abdurrahman Tufan, Silvana Guerriero, Gaafar Mohamed Ragab, Jurgen Sota, Stefano Gentileschi, Stefania Costi, Ibrahim A Almaghlouth, Andrea Hinojosa-Azaola, Samar Tharwat, Tadej Avčin, 2024, original scientific article Abstract: Introduction: This study aims to characterize ocular manifestations of juvenile Behçet’s disease (jBD). Methods: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. Results: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) μm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. Conclusions: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.
Keywords: autoinflammatory diseases, Behçet’s disease, paediatric ophthalmology, rare disease registries, retinal vasculitis, uveitis
Published in DiRROS: 15.06.2026; Views: 205; Downloads: 110
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3. Comprehensive care and education can improve nutritional and growth outcomes in children with persistent cow’s milk, egg, or peanut allergies : a five-year follow-up study of nutritional statusTomaž Poredoš, Tina Vesel, Anja Koren Jeverica, Mojca Zajc Avramovič, Gašper Markelj, Nina Emeršič, Tadej Avčin, 2024, original scientific article Keywords: food allergy, children, adequate nutrition, nitric oxide, physical activity, beetroot, football
Published in DiRROS: 15.06.2026; Views: 136; Downloads: 125
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4. Dynamics of serum levels of TNF-α in a longitudinal follow-up study in 98 patients with juvenile idiopathic arthritis treated with anti-TNF-α biological drugsNataliia Morozova, Mojca Zajc Avramovič, Gašper Markelj, Nataša Toplak, Tadej Avčin, 2024, original scientific article Abstract: Objective: To determine the dynamics of serum levels of TNF-α in patients with juvenile idiopathic arthritis (JIA) treated with anti-TNF-α biological drugs and investigate their association with the disease activity. Methods: We conducted a single-centre, observational cohort study in 98 patients with JIA (30 boys, 68 girls, mean age 11.3 years) treated with anti-TNF-α biological drugs. Clinical examinations and laboratory assessments of serum levels of TNF-α were performed before starting therapy with biological drug and at 6-month intervals afterwards up to 2.5 years. Results: The analysis of serum levels of TNF-α in relation to the disease activity states showed the highest mean serum levels of TNF-α in patients on etanercept who had low disease activity states and in patients on adalimumab who had inactive disease. The correlation analysis in patients with JIA treated with etanercept or adalimumab showed a weak negative correlation between the serum levels of TNF-α and JADAS10 scores (p = 0.007), (r = - 0.177). Conclusion: The assessment of serum levels of TNF-α in children with JIA during treatment with etanercept or adalimumab is not a reliable biomarker of disease activity or immunological remission. Longitudinal measurement of TNF-α has no added clinical value in patients with JIA treated with anti-TNF-α biological drugs. Key Points • There is limited evidence regarding the effect of anti-TNF therapy on serum concentrations of TNF-α in patients with juvenile idiopathic arthritis • Our study showed an increase in the serum level of TNF-α after the initiation of therapy with either etanercept or adalimumab, which was more significant in patients with inactive or low disease activity • Serum TNF-α is most likely not biologically active during therapy with TNF-α inhibitors and therefore not a reliable biomarker of disease activity or immunological remission in patients with juvenile idiopathic arthritis
Keywords: adalimumab, cytokines, etanercept, juvenile idiopathic arthritis, tumour necrosis factor-alpha
Published in DiRROS: 05.06.2026; Views: 201; Downloads: 86
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5. Defining remission in childhood-onset lupus : PReS-endorsed consensus definitions by an international task forceEve Mary Dorothy Smith, Amita Aggarwal, Jenny Ainsworth, Eslam Al-Abadi, Tadej Avčin, Lynette Bortey, Jon Burnham, Coziana Ciurtin, Christian M. Hedrich, Sylvia Kamphuis, 2024, original scientific article Abstract: Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Method:s The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.
Keywords: autoinflammatory diseases, lupus, treat-to-target, remission, children
Published in DiRROS: 05.06.2026; Views: 153; Downloads: 124
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6. Increased frequency of circulating activated FOXP3+ regulatory T cell subset in patients with chronic lymphocytic leukemia is associated with the estimate of the size of the tumor mass, STAT5 signaling and disease course during follow-up of patients on therapyZlatko Roškar, Mojca Dreisinger, Evgenija Homšak, Tadej Avčin, Sebastjan Bevc, Aleš Goropevšek, 2024, original scientific article Keywords: chronic lymphocytic leukemia, signal transduction, cytokines, T cells
Published in DiRROS: 04.06.2026; Views: 191; Downloads: 143
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7. Long-term follow-up of 109 children with juvenile idiopathic oligoarthritis after first intra-articular corticosteroid injectionMojca Zajc Avramovič, Nataša Toplak, Gašper Markelj, Nina Emeršič, Tadej Avčin, 2024, original scientific article Abstract: 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
Keywords: ANA, biologic therapy, HLA B27, juvenile idiopathic arthitis, long-term follow-up, methotrexate, oligoarthritis, outcome, pediatric arthritis
Published in DiRROS: 04.06.2026; Views: 178; Downloads: 132
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8. Epidemiology and management of malignancies in patients with inborn errors of immunity - an ESID registry study of 19,959 patientsDelfien J. A. Bogaert, Christina Helene Wolfsberger, Andishe Attarbaschi, Jonathan Gathmann, Klaus Warnatz, Gabriele Mueller, Anna Mukhina, Stephan Rusch, Gerhard Kindle, Joris M. van Montfrans, Markus G. Seidel, 2026, original scientific article Abstract: Background Inborn errors of immunity (IEI), or primary immune disorders (PIDs), predispose individuals to infections, autoimmunity, inflammation, allergy, and malignancy. Malignancies are a major cause of morbidity and mortality in patients with IEI/PIDs, with poorer outcomes compared with the general population. Objective We sought to determine the frequency and types of malignancies in patients with IEI/PIDs and to assess clinical management approaches across Europe. Methods Descriptive analyses were performed on malignancy data within each IEI category. In addition, a European Society for Immunodeficiencies Registry survey (05/2022-03/2024) collected data on management strategies and challenges. Results Of 19,959 patients with IEI/PIDs, 1783 (8.9%) developed malignancies, of whom 27.1% presented malignancy as first manifestation of IEI/PIDs. A total of 1210 malignancies were specified; B-cell non-Hodgkin lymphoma was most common (24.2%). Detailed malignancy-IEI/PID association maps are provided. Predominantly antibody deficiencies accounted for 59.1% of malignancy cases, with a higher median age at first malignancy (43.6 years) compared with other IEI/PID categories, for example, combined immunodeficiencies with syndromic or associated features (11.7 years). Survey findings revealed that oncological treatment was modified because of IEI/PIDs in 21.5% of cases, with assumed negative impacts of IEI/PIDs on complications and outcomes (in 27.4% and 30.7%, respectively). IEI/PIDs influenced transplant decisions in 16.5% of cases. Management practices such as interdisciplinary decision finding and guideline availability were recorded. Conclusions This study provides comprehensive epidemiological data on malignancies in IEI/PIDs, highlighting the need for tailored screening and management. Survey results emphasize the real-world challenges and support the development of IEI/PID-specific oncological surveillance guidelines and treatment strategies.
Keywords: inborn errors of immunity, IEI, primary immunodeficiency, PID, primary immune disorder, malignancy, cancer predisposition syndromes, tumor predisposition, ESID registry
Published in DiRROS: 08.04.2026; Views: 245; Downloads: 226
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9. Machine learning-assisted diagnosis classification of primary immune dysregulation using IDDA2.1 phenotype profilingMalte Schwitzkowski, Sai Pavan Kumar Veeranki, Benedikt N. Seidel, Gerhard Kindle, Stephan Rusch, Diether Kramer, Markus G. Seidel, 2026, original scientific article Abstract: Background Immune dysregulation, including autoimmunity, autoinflammation, allergy, and malignancy predisposition, adds significant disease burden in primary immune disorders (PID) and inborn errors of immunity (IEIs). Objective We evaluated whether the 5-graded immune deficiency and dysregulation activity (IDDA2.1) score, encompassing 21 organ involvement and disease burden parameters, supports diagnosis across a wide spectrum of IEIs. Methods From April 2022 to November 2024, collaborators from 84 centers collected 1,043 IDDA score datasets from 825 patients across 89 IEIs (17 disorders with ≥10 patients each; range, 1-196 per IEI), including 177 scores from 141 treated patients. Supervised machine learning models ( k -nearest neighbors, support vector machine, logistic regression, random forest) classified patients into disease groups and ranked corresponding predictive features, while unsupervised uniform manifold approximation and projection (UMAP) visualized disease-specific clustering. Results Feature analysis reflected clinicians’ recognition of IEI patterns and confirmed internal IDDA score consistency. Phenotype profiles in treated patients remained informative, inversely reflecting anticipated treatment-dependent phenotype amelioration. UMAP effectively distinguished IEIs by IDDA2.1 profiles. Genetic disorder prediction achieved 73% overall accuracy, 70% for the correct monogenic IEI, and 93% within the top 3 predictions; classification reached 43% for IEI–International Union of Immunological Society categories and 59% for 12 “cardinal” IEIs (25 genes). Conclusions Random forest feature importance analysis can inform targeted clinical screening for key disease manifestations. The top 3 prediction approach demonstrates diagnostic potential, but improved accuracy will require larger, globally shared datasets. Small sample sizes for rare diseases highlight the necessity of broader collaboration to enhance AI-assisted clinical decision-making in the future.
Keywords: inborn error of immunity, IEI, primary immune regulatory disorder, PIRD, phenotype-driven disease classification, interoperable patient data, immune deficiency and dysregulation activity (IDDA) score, artificial intelligence, AI, unsupervised and supervised machine learning, ML, primary immune disorder, PID
Published in DiRROS: 08.04.2026; Views: 304; Downloads: 251
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10. Anakinra during pregnancy and lactation for corticosteroid-dependant colchicine-resistant recurrent pericarditis in a patient with neutralizing anti-interleukin-1 receptor antagonist antibodies : a case reportAndreja Černe Čerček, Alja Gomišček, Andreja Trojner-Bregar, Tadej Avčin, Christoph Kessel, Lorenz Thurner, Natalie Fadle, Miha Čerček, 2025, other scientific articles Abstract: Background Failure of a small surgical aortic bioprosthesis represents a challenging clinical scenario with valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) often resulting in patient-prosthesis mismatch. Bioprosthetic valve fracture (BVF) performed as a part of the ViV TAVI has recently emerged as an alternative approach with certain types of surgical bioprostheses. Case summary An 81-year-old woman with a history of three surgical aortic valve procedures presented with heart failure. Aortic bioprosthesis degeneration with severe stenosis and moderate regurgitation was found. The patient was deemed a high-risk surgical candidate and the heart team decided that ViV TAVI was the preferred treatment option. Due to the very small 19 mm stented surgical aortic bioprosthesis Mitroflow 19 mm (Sorin Group, Italy) we decided to perform BVF as a part of ViV TAVI to prevent patient-prosthesis mismatch. Since this was the first BVF procedure in our centre, an ex vivo BVF of the same kind of bioprosthetic valve was performed first. Subsequently, successful BVF with implantation of Evolut R 23 mm (Medtronic, USA) self-expandable transcatheter valve was performed. Excellent haemodynamic result was achieved and no periprocedural complications were present. The patient had an immediate major improvement in clinical status and remains asymptomatic after 6-months. Discussion Bioprosthetic valve fracture together with ViV TAVI is a safe and effective emerging technique for treatment of small surgical aortic bioprosthesis failure. Bioprosthetic valve fracture allows marked oversizing of implanted self-expandable transcatheter aortic valves, leading to excellent haemodynamic and clinical results. An ex vivo BVF can serve as an important preparatory step when introducing the new method.
Keywords: recurrent pericarditis, case report, anakinra, antibodies against il-1 receptor antagonists, pregnancy
Published in DiRROS: 24.02.2026; Views: 342; Downloads: 237
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