Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs

Abstract

IntroductionBiological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.MethodsThe study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.ResultsBaseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).ConclusionsCXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.

Stromal Cells in Chronic Inflammation and Tertiary Lymphoid Organ Formation

“…Researchers have revised this model recently, and they have not confirmed a clear association between TLO formation and poor disease outcome (176). The levels of the chemokine CXCL13 appear to correlate with disease severity and persistence of subclinical synovitis, as assessed by ultrasound (177). TLOs have also been found in the subchondral bone in erosive RA and implicated in local osteoclast activation and tissue damage (178).…”

CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis – from bench to bedside?

“…Therefore, CXCL13 serum levels cannot be used to distinguish between an active autoimmune response and severe infectious diseases. It has to be considered that CXCL13 serum levels are also elevated significantly in other diseases, such as rheumatoid arthritis, Lyme borreliosis, Sjögrens' syndrome and idiopathic pulmonary fibrosis [43][44][45][46]. Therefore comorbidities should be ruled out for a source of CXCL13 production.…”

The Time Course of Changes in Biomarker Levels and the Ultrasonic Signs of Inflammation in Patients With Rheumatoid Arthritis

“…[47], по данным которых низ-кий базальный уровень ИЛ6 являлся «предиктором» кли-нического эффекта (DAS28 <3,2) у пациентов, получав-ших лечение гуманизированными моноклональными ан-тителами к ИЛ6-рецептору -тоцилизумабом. Выявлен другой перспективный биомаркер определяемого по УЗИ синовита -хемокин CXCL13, концентрация которого коррелирует с базальной клинической активностью РА и наличием воспаления на фоне терапии, независимо от исходной активности синовита по данным УЗИ, динами-ки клинической активности, концентрации острофазо-вых белков и аутоантител [32]. Представляет также инте-рес тот факт, что данные ЭД и СШ хорошо коррелируют с экспрессией генов широкого спектра «провоспалитель-ных» медиаторов (ФНОα, ИЛ1β, СЭФР и в меньшей сте-пени ИЛ6) в синовиальной ткани пациентов с РА, полу-ченной с помощью биопсии [7].…”

“…Несмотря на существование большого числа иссле-дований, касающихся анализа цитокинов и других «про-воспалительных» и «ангиогенных» биомаркеров для оцен-ки особенностей течения РА [28], имеются лишь единич-ные работы, выполненные на небольшом клиническом материале, посвященные изучению их связи с выявляе-мым на УЗИ синовитом [29][30][31][32][33][34]. Это и обусловило прове-дение нашего исследования, в которое были включены па-циенты с ранним РА, получавшие терапию в соответствии с концепцией «Лечение до достижения цели».…”