Whole exome sequencing in patients with childhood-onset systemic lupus erythematosus: Results from a Croatian national study.

The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients.

Glutathione S-Transferase Gene Polymorphisms as Predictors of Methotrexate Efficacy in Juvenile Idiopathic Arthritis.

Because of the unpredictable efficacy of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA), the possibility of a favourable outcome is reduced in more than 30% of patients. To investigate the possible influence of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene deletion polymorphisms on MTX efficacy in patients with JIA, we determined these polymorphisms in 63 patients with JIA who did not achieve remission and 46 patients with JIA who achieved remission during MTX therapy. No significant differences were observed in the distribution of single GSTM1 or GSTT1 deletion polymorphisms or their combination between the two groups: 58.

Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV).

The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls.

Serum Levels of S100A8/A9 as a Biomarker of Disease Activity in Patients with IgA Vasculitis.

S100A8/A9 protein is a well-known marker of disease activity or severity in many autoimmune and autoinflammatory diseases, but there have not been many studies about the role of S100A8/A9 in IgA vasculitis (IgAV). The aim of our study was to evaluate S100A8/A9 as a possible biomarker of activity in IgAV. We measured the serum levels of S100A8/A9 in pediatric patients with IgA vasculitis at the onset of the disease, after three months, and after six months.

Erythrocyte Glutathione S-Transferase Activity as a Sensitive Marker of Kidney Function Impairment in Children with IgA Vasculitis.

IgA vasculitis (IgAV) is the most common childhood vasculitis. The main cause of morbidity and mortality in children with IgAV is nephritis (IgAVN), but the risk of its development, severity, and chronicity remain unclear. Erythrocyte glutathione S-transferase (e-GST) activity has been previously detected as a sensitive marker of kidney function impairment in several diseases.

Involvement of M1-Activated Macrophages and Perforin/Granulysin Expressing Lymphocytes in IgA Vasculitis Nephritis.

We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli.

ASSOCIATION BETWEEN HIGH MOBILITY GROUP BOX 1 PROTEIN GENE (rs41369348) POLYMORPHISM AND IMMUNOGLOBULIN A VASCULITIS IN CHILDREN.

Immunoglobulin A vasculitis (IgAV) or Henoch-Schönlein purpura is the most prevalent systemic small vessel vasculitis in childhood. High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a pro-inflammatory signal, important for the activation of antigen-presenting cells and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases.

HLA Polymorphisms and Clinical Manifestations in IgA Vasculitis.

Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study.

The Association of HMGB1 and RAGE Gene Polymorphisms with IgA Vasculitis.

High-mobility group box 1 (HMGB1) is a pleiotropic cytokine that propagates inflammation by its extracellular action of interacting with the receptor for advanced glycation end products (RAGE). Both HMGB1 and RAGE play multiple roles in the pathogenesis of a variety of inflammatory and autoimmune diseases. We investigated the association of five single-nucleotide polymorphisms (SNPs) of the HMGB1 gene (rs1412125, rs2249825, rs1045411, rs1060348, rs41369348) and four SNPs of the RAGE gene (rs1800624, rs1800625, rs2070600, rs3134940) with the susceptibility and clinical features of paediatric patients with IgA vasculitis (IgAV), also known as Henoch-Schönlein's purpura.

Clinical features, treatment and outcome of pediatric patients with severe cutaneous manifestations in IgA vasculitis: Multicenter international study.

Objective: IgA vasculitis (IgAV) (formerly Henoch-Schönlein Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course.

Methods: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses.

Semiquantitative classification (SQC) and Oxford classifications predict poor renal outcome better than The International Study of Kidney Disease in Children (ISKDC) and Haas in patients with IgAV nephritis: a multicenter study.

Introduction: Several histologic classifications are used in the evaluation of IgA vasculitis nephritis (IgAVN), however, to date, no studies have determined which one has the strongest association with the severity of IgAVN and, as a consequence, its outcomes.

Materials And Methods: Patients included in the study were diagnosed with IgAV and IgAVN in seven tertiary university medical centers in Croatia, Italy and Israel. The International Study of Kidney Disease in Children (ISKDC), Haas, Oxford, and Semiquantitative classification (SQC) classifications were used in the analysis and description of renal biopsy.

Gastrointestinal involvement and its association with the risk for nephritis in IgA vasculitis.

Background: We analysed clinical and biochemical parameters in predicting severe gastrointestinal (GI) manifestations in childhood IgA vasculitis (IgAV) and the risk of developing renal complications.

Methods: A national multicentric retrospective study included children with IgAV reviewed in five Croatian University Centres for paediatric rheumatology in the period 2009-2019.

Results: Out of 611 children, 281 (45.

Persistence and Severity of Cutaneous Manifestations in IgA Vasculitis Is Associated with Development of IgA Vasculitis Nephritis in Children.

Background/objective: The purpose of this study was to evaluate the prevalence and severity of skin involvement in children with IgA vasculitis (IgAV) and its relationship with clinical and biochemical parameters and the risk of developing IgA vasculitis nephritis (IgAVN), the only cause of long-term morbidity and the main prognostic factor in IgAV patients.

Methods: This national multicenter retrospective study included 611 patients under the age of 18 years with IgAV referred to five Croatian tertiary hospitals between 2009 and 2019. Patient data were collected from a database with systematic analysis of IgAV patients in the Croatian population.

Geospatial clustering of childhood IgA vasculitis and IgA vasculitis-associated nephritis.

Objectives: Research on spatial variability of the incidence of IgA vasculitis (IgAV) in children and its potential implications for elucidation of the multifactorial aetiology and pathogenesis is limited. We intended to observe spatial variability of the incidence of IgAV and IgA vasculitis-associated nephritis (IgAVN) using modern geostatistical methods, and hypothesised that their spatial distribution may be spatially clustered.

Methods: Patients' data were retrospectively collected from 2009 to 2019 in five Croatian University Hospital Centres for paediatric rheumatology, and census data were used to calculate the incidence of IgAV.

Rituximab in Treatment of Children with Refractory Vasculitis and Systemic Lupus Erythematosus - Single Center Experience in Croatia.

The aim of this study was to present our experience in rituximab therapy in patients with childhood-onset systemic lupus erythematosus, lupus nephritis, and ANCA-associated vasculitis. We conducted a retrospective clinical chart review of all patients treated with rituximab in the time period from January 2009 to December 2015. Eight patients (3 boys and 5 girls) aged 8 to 15 at the onset of disease were treated with rituximab.

HOW TO TREAT PATIENTS AFTER SERIOUS ADVERSE EFFECTS CAUSED BY TNF INHIBITORS?

Biological agents are widely used in the treatment of autoimmune rheumatic disorders. We report on serious adverse events during treatment with anti-tumor necrosis factor antibody in two of our patients with juvenile idiopathic arthritis. One patient was treated with a biological agent due to juvenile idiopathic arthritis complicated by uveitis, developing miliary tuberculosis during treatment.

Quality of life in children suffering from juvenile idiopathic arthritis-associated uveitis.

Uveitis (JIA-U), the most common extra-articular manifestation in juvenile idiopathic arthritis (JIA), may cause severe impairment of vision in children and affect their quality of life (QoL). Considering the lack of uveitis-related QoL assessment questionnaire, and multidimensional nature of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), commonly used for monitoring and assessing the health status of children with JIA, we performed a cross-sectional study to investigate the potential of the JAMAR in estimation of QoL in children suffering from JIA-U. The study included 42 children with JIA, 21 of whom had JIA-U.

Comparison of Different Diagnostic Guidelines for the Diagnosis of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: Single Centre Experience.

Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA), caused by exaggerated but ineffective immune response. The aim of the study was to compare the capacity of the HLH-2004 guidelines with the capacity of the MAS guidelines from 2005, and with the new set of classification criteria from 2016 in diagnosing MAS complicating sJIA. The study included 35 children aged 1-18 diagnosed with sJIA according to ILAR criteria and treated at the Department of Pediatrics, Division of Immunology and Rheu-matology, Zagreb University Hospital Centre, in the period from 2009 to 2015.