AIM To determine whether demographic data, clinical features, and laboratory variables at disease onset can predict the response to methotrexate in juvenile idiopathic arthritis (JIA) patients. METHODS A cohort of 143 newly diagnosed JIA patients initially treated with methotrexate was enrolled in this study. Demographic, clinical, and laboratory parameters were analysed using univariate and multivariate logistic regression to identify predictors of response to methotrexate. The variables included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelets, IgA, IgG, the number of active joints and age at disease onset. Treatment response was assessed at six months, with patients classified as responders (those who achieved clinically inactive disease according to the American College of Rheumatology - ACR criteria) or non-responders. RESULTS Poor response to methotrexate was associated with the number of active joints (p=0.0001; OR=2.7), baseline levels of CRP (p=0.044; OR=1.138), IgA (p=0.004; OR=2.159), and platelet count (p=0.01; OR=1.05). IgG level (P=0.236) did not correlate with the treatment response. CONCLUSION We identified widely available and clinically acceptable biomarkers that can be utilized as predictive indicators of response to methotrexate in JIA patients.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

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.

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

P381 Transient periosteal hyperostosis with dysproteinemia (Goldbloom syndrome): two cases report Riccardo Papa, Alessandro Consolaro, Francesca Minoia, Roberta Caorsi, Gianmichele Magnano, Marco Gattorno, Angelo Ravelli, Paolo Picco Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy; Radiologia, Istituto Giannina Gaslini, Genoa, Italy Presenting author: Riccardo Papa Pediatric Rheumatology 2017, 15(Suppl 1):P381

Background PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum and acne) is a rare autosomal-dominant autoinflammatory disease caused by mutations in PSTPIP1gene. Typically presents with recurrent sterile, erosive arthritis in childhood, occurring spontaneously or after minor trauma, occasionally resulting in significant joint destruction. By puberty, joint symptoms tend to subside and cutaneous symptoms increase. Cutaneous manifestations include pathergy, frequently with abscesses at the sites of injections, severe cystic acne, and recurrent nonhealing sterile ulcers, often diagnosed as PG.