A prediction rule for polyarticular extension in oligoarticular-onset juvenile idiopathic arthritis

Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers

“…The demographic (age and sex) and main clinical features of patients and control subjects, various laboratory parameters and known markers of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and anti-nuclear antibodies (ANA), the number and type of active joints at onset, therapeutic regimens administered after diagnosis, disease oligoarticular or polyarticular course, and iridocyclitis development within a 2 years follow-up period are reported in Table 1 . The 2 years follow up was set up because polyarticular extension in OJIA occurs more frequently within this time after initial disease presentation ( 9 ). Mean patient age at onset was 5.2 years and female/male ratio was 25 (55,6%)/20 (44,4%), whereas mean control subject age was 7.2 years and female/male ratio was 13 (54.2%)/11 (45.8%).…”

“…Our data extend previous findings showing the abundance of two acute phase proteins, CRP and SAA1, as “free” molecules in the circulation of JIA patients. Increased CRP serum levels in the first 6 months of disease have been associated with OJIA polyarticular course, making this protein a candidate predictor of extension ( 9 ). Higher SAA1 serum levels were demonstrated in JIA patients vs healthy CTR correlating with the number of active joints, iridocyclitis development, and high CRP and ESR expression, suggesting its potential as a disease activity marker ( 63 , 106 ).…”

“…On the other hand, proteins associated to ANA positivity, polyarticular extension, iridocyclitis development, and relapse were endowed with stimulatory effects on inflammatory/innate immune responses. Among them, some have been previously linked to JIA pathogenesis and severity and regarded as potential prognostic biomarkers, such as CRP ( 9 ), MMP9 ( 163 ), SPP1 ( 7 , 164 , 165 ), and MPO ( 166 ). Interestingly, MPO was reported to be highly enriched in neutrophil-derived EVs from the SF of RA patients ( 31 ) and suggested to mediate their destructive effects in RA.…”

“…Although the majority maintains an oligoarticular phenotype (≤4 joints), which is more benign and likely to achieve remission in response to first-line treatment (non-steroidal anti-inflammatory drugs or intra-articular glucocorticoids), a relevant percentage of them (21-39.5%) presents a polyarticular (extended) course of arthritis (involvement of ≥5 joints), which is often erosive and treatment refractory requiring more aggressive therapies ( 9 ). Despite significant advances in OJIA treatment have been obtained in the last decades due to the availability of new therapeutic agents and the possibility to perform controlled clinical trials ( 1 ), up to 40% OJIA patients do not respond adequately to therapies or fail to achieve sustained drug-free clinical remission, showing disease relapse in treated joints and/or progressive spread to other joints by one-two years after onset ( 3 , 9 , 10 ). Early diagnosis and prediction of disease course/outcome and iridocyclitis development in individual patients in the early stages are critical to tailor therapeutic intervention but are hindered by the lack of validated biomarkers ( 11 – 13 ).…”

“…Early diagnosis and prediction of disease course/outcome and iridocyclitis development in individual patients in the early stages are critical to tailor therapeutic intervention but are hindered by the lack of validated biomarkers ( 11 – 13 ). To date, only a few molecular, immune, and clinical markers have, in fact, been proposed ( 9 , 14 – 17 ). Therefore, a great deal of efforts is currently being expended in the search of new biomarkers readily measurable in patient-derived material at an early stage of the disease and in a minimally invasive way ( 12 , 18 , 19 ).…”