Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.

Recurrent urinary tract infections (rUTI) represent a major healthcare and economic burden along with a significant impact on patient’s morbidity and quality of life, even in the absence of well-known risk factors, such as vesicoureteral reflux. Despite numerous attempts to find a suitable therapeutic option, there is no clear benefit of any currently available intervention for prevention of UTI recurrence and its long-term consequences such as hypertension, renal scarring and/or insufficiency. The common treatment practice in many centers around the globe involves the use of continuous low-dose antibiotic prophylaxis, irrespective of various studies indicating increased microbial resistance against the prophylactic drug, leading to prolonged duration and escalating the cost of UTI treatment. Moreover, the rapid appearance of multi-drug resistant uropathogens is threatening to transform UTI to untreatable disease, while impaired host-microbiota homeostasis induced by a long-term use of antibiotics predisposes patients for various autoimmune and infectious diseases. New biomarkers of the increased risk of UTI recurrence could therefore assist in avoiding such outcomes by revealing more specific patient population which could benefit from additional interventions. In this light, the recent findings suggesting a crucial role of urothelial innate immunity mechanisms in protection of urinary tract from invading uropathogens might offer new diagnostic, prognostic and even therapeutic opportunities. Uroepithelial cells detect uropathogens via pattern recognition receptors, resulting in activation of intracellular signaling cascade and transcription factors, which ultimately leads to an increased production and secretion of chemokines, cytokines and antimicrobial peptides into the urinary stream. Emerging evidence suggest that the disturbance of a single component of the urinary tract innate immunity system might increase susceptibility for rUTI. The aim of the current review is to update clinicians and researchers on potential biomarkers of host immune response alterations predisposing for rUTI and propose those well worth exploring further. For this purpose, over a hundred original papers were identified through an extensive PubMed and Scopus databases search. This comprehensive review might enrich the current clinical practice and fill the unmet clinical needs, but also encourage the development of therapeutic agents that would facilitate urinary bacterial clearance by enhancing the host immune response.

Enthesitis related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA), often regarded as an undifferentiated form of juvenile spondyloarthritis (jSpA). While gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in ERA patients is largely unknown. The aim of this study was to measure the concentration of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with different subtypes of JIA, as well as to correlate the results with various demographic, clinical, laboratory, imaging, and treatment characteristics. The cross-sectional exploratory study involving 71 patients with ERA, other forms of JIA and children complaining musculoskeletal symptoms was therefore conducted. Along with fCAL assessment, a detailed clinical and laboratory examination was performed, including the calculation of a composite disease activity scores. Moreover, MRI of the sacroiliac joints was performed in all ERA and other patients complaining of low back pain. The median concentration of fCAL was highest in ERA patients (33.2 mg/kg, p = 0.02), with a significant difference between those with inactive and active disease (20.0 vs. 57.4, p = 0.01), as well as those with and without MRI signs of sacroiliitis (22.6 vs. 54.3, p = 0.04). The fCAL did not differ depending on the NSAID use (23 vs. 20, p = 0.18), although weak correlation was observed with the treatment duration (r = 0.25, p = 0.03). In conclusion, our findings indicate that a parallel inflammation in musculoskeletal system and gut can occur not just in adults with SpA, but in children with ERA as well.

Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches.

Type I interferons (IFN) have important roles in many immune-mediated inflammatory diseases (IMIDs) and are a relatively new therapeutic target. Direct detection of type I IFNs has proved challenging, thus their presence is often inferred from the expression of interferon-stimulated genes (ISGs) and calculation of an interferon score (IS). The objective of this research was to determine if the expression of six common ISGs and subsequent IS were comparable when RNA was derived from the Tempus and PAXgene whole blood RNA collection systems. Whole blood was obtained from ten healthy adults, incubated ex vivo in the absence and presence of recombinant human IFNα then divided into PAXgene and Tempus tubes. Despite reports of tube-specific patterns of gene expression, quantitative PCR (qPCR) analysis revealed no significant differences between PAXgene and Tempus tubes in either the homeostatic or IFNα-induced expression of six ISGs (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1). Overall there was a strong correlation in the IS between unstimulated (r = 0.92, p = 0.0005) and IFNα-stimulated (r = 0.71, p = 0.0268) samples derived from the PAXgene and Tempus tubes.

The Paediatric Rheumatology European Society (PReS) has over many years, developed a portfolio of educational activities to address increasing educational needs of workforce and support young clinicians to acquire skills to develop new knowledge and deliver clinical care in the future. These educational activities aim to facilitate growth of paediatric rheumatology and ultimately improve the clinical care for children and families. This article describes the current portfolio of PReS educational activities and their relevance to the international paediatric rheumatology community.