Increased CD21-CD27- atypical memory B cells as a biomarker of clinical disease activity in patients with systemic lupus erythematosus

Background Determining disease activity in systemic lupus erythematosus (SLE) patients is challenging and limited by the lack of reliable biomarkers. Analysis of the altered distribution of circulating B cells has shown promise for assessment disease activity. Yet studies are limited by variable classifications of B subsets. Therefore, we studied peripheral B cells using high-dimensional tools to identify a valid biomarker of disease activity.Methods We studied B cells in two separate cohorts of patients included in the Swiss SLE Cohort Study. In discovery cohort A, we analyzed cryopreserved PBMCs from 30 SLE, and 30 age-, sex- and ethnicity matched healthy controls (HC) by mass cytometry. In validation cohort B, fresh blood from 63 SLE, 14 Sjögren syndrome (pSS), 14 Sarcoidosis (Sarc), and 39 age-matched HC were analyzed by flow cytometry.Results In cohort A, using unsupervised clustering analysis, we identified 7 metaclusters within B cells. Two metaclusters were increased in SLE and exhibited a phenotype of atypical memory B cells (aMBC): CD21-, CD27-, CD11c+ and CXCR5-. Based on cohort A results, we confirmed in cohort B the increase in CD21-CD27- aMBC in SLE, compared to healthy and disease controls. In both cohorts, aMBC were associated with the severity of clinical manifestations. Compared to classical biomarkers, aMBC showed a significant correlation with clinical signs of disease activity. Conclusion aMBC were expanded in SLE, and the increase correlated with clinical disease activity. According to our data, aMBC represents a robust and easily accessible biomarker to assess disease activity in patients with SLE.

Dr. Kremer et al reply

Drs. Pincus, Bergman, and Yazici have raised some concerns about our published article comparing the Clinical Disease Activity Index (CDAI) with simultaneous measures of the Routine Assessment of Patient Index Data 3 (RAPID3).1 We believe our publication has clearly established that the validated CDAI scores provide a fundamentally different evaluation of disease status compared with the RAPID3.

Should Quantitative Measures and Management of Rheumatoid Arthritis Include More Than Control of Inflammatory Activity?

We agree strongly with Kremer et al that "metrics are essential for evaluating disease activity in patients with rheumatoid arthritis (RA)."1 Nonetheless, data reported from the Corrona and the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registries for Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) are quite similar to those reported in the initial 2008 RAPID3 report.2

A Novel Digital Care Management Platform to Monitor Clinical and Subclinical Disease Activity in Multiple Sclerosis

In multiple sclerosis (MS), the early detection of disease activity or progression is key to inform treatment changes and could be supported by digital tools. We present a novel CE-marked and FDA-cleared digital care management platform consisting of (1) a patient phone/web application and healthcare professional portal (icompanion) including validated symptom, disability, cognition, and fatigue patient-reported outcomes; and (2) clinical brain magnetic resonance imaging (MRI) quantifications (icobrain ms). We validate both tools using their ability to detect (sub)clinical disease activity (known-groups validity) and real-world data insights. Surveys showed that 95.6% of people with MS (PwMS) were interested in using an MS app, and 98.2% were interested in knowing about MRI changes. The icompanion measures of disability (p < 0.001) and symptoms (p = 0.005) and icobrain ms MRI parameters were sensitive to (sub)clinical differences between MS subtypes. icobrain ms also decreased intra- and inter-rater lesion count variability and increased sensitivity for detecting disease activity/progression from 24% to 76% compared to standard radiological reading. This evidence shows PwMS’ interest, the digital care platform’s potential to improve the detection of (sub)clinical disease activity and care management, and the feasibility of linking different digital tools into one overarching MS care pathway.

Corneal inflammatory cell infiltration predicts disease activity in chronic inflammatory demyelinating polyneuropathy

The assessment of disease activity is fundamental in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Previous studies with small patient numbers found an increase of corneal immune cell infiltrates as a potential marker of inflammation in patients with CIDP. However, its clinical relevance remained unclear. The present study aimed to determine whether the amount of corneal inflammatory cells (CIC) measured by corneal confocal microscopy (CCM) detects disease activity in CIDP. CIC were measured in 142 CCM-investigations of 97 CIDP-patients. Data on clinical disease activity, disability (INCAT-ODSS) and need for therapy escalation at the timepoint of CCM, 3 and 6 months later were analyzed depending CIC-count. Pathological spontaneous activity during electromyography was examined as another possible biomarker for disease activity in comparison to CIC-count. An increased CIC-count at baseline was found in patients with clinical disease activity and disability progression in the following 3–6 months. An increase to more than 25 CIC/mm2 had a sensitivity of 0.73 and a specificity of 0.71 to detect clinical disease activity and a sensitivity of 0.77 and a specificity of 0.64 to detect disability progression (increasing INCAT-ODSS) in the following 6 months. An increase to more than 50 CIC/mm2 had a sensitivity of about 0.51 and a specificity of 0.91 to detect clinical disease activity and a sensitivity of 0.53 and a specificity of 0.80 to detect disability progression. CIC count is a non-invasive biomarker for the detection of disease activity in the following 6 months in CIDP.

Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan

Background To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. Methods We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. ‘Power Doppler (PD) responder’ was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. Results Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23–0.91, p = 0.043) was an independent predictor of PD responder status. Conclusion Serum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept. Trial registration Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657

AB0130 QUESTIONING THE USEFULNESS OF CDAI AS A MEASURE OF DISEASE ACTIVITY IN A TREAT TO TARGET PROGRAMME

Background:Rheumatoid arthritis (RA) is a chronic autoimmune condition which if not treated can lead to joint destruction and long term disability. In RA, the concept of T2T is recommended as the appropriate method to manage early arthritis 1. It has shown promising results to achieve clinical remission (CR) or low disease activity (LDA) 2.Objectives:The objective of this study was to investigate the potential to achieve remission or LDA according to the Clinical Disease Activity Index (CDAI) for RA, during treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and Biologics, and the factors that affect the remission/LDA outcome.Methods:We performed an observational prospective study on patients’ data available from our Early Arthritis Cohort. All patients with newly diagnosed RA who met the American College of Rheumatology (ACR) criteria were enrolled. Patients are managed by an Advanced Nurse Practitioner (ANP) with consultant supervision. To assess their response to treatment, we used the Clinical Disease Activity Index3. Analysis was performed using SPSS.Results:Out of a total of 459 patients, 353 completed the programme. 217 patients (61.5%) were female and (136) 38.5 % were male. Mean age was 53.98 (SD 14.66). 195 patients were on monotherapy, 40 on combination DMARDs and 115 were on Biologics/Janus Kinase Inhibitors (JAK-Inh). Remission-rates in the monotherapy and combination DMARDs groups were approximately 60%, whilst the remission rate in the Biologics/JAK-Inh group was 41.7%. Amongst female patients 15.9% had erosions on X-ray at the time of diagnosis whilst the equivalent figure for male patients was 29.6%.Conclusion:An association between male gender and the likelihood of erosions on X-Ray was observed. In addition an association between final medication and outcome was observed. An increased likelihood of non-remission was noted in patients that required escalation to Biologics/JAKs. A possible explanation for the lower levels of remission seen throughout the groups is the difficulty in achieving remission under the CDAI score as compared to DAS-28.References:[1]Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Annals of the Rheumatic Diseases. 2016;75(1):3.[2]Scott IC, Ibrahim F, Panayi G, Cope AP, Garrood T, Vincent A, Scott DL, Kirkham B; TITRATE Programme Investigators. The frequency of remission and low disease activity in patients with rheumatoid arthritis, and their ability to identify people with low disability and normal quality of life. Semin Arthritis Rheum. 2019 Aug;49(1):20-26. doi: 10.1016/j.semarthrit.2018.12.006. Epub 2018 Dec 28. PMID: 30685064.Disclosure of Interests:None declared