Precision Medicine in Rheumatoid Arthritis

Bluett, James; Barton, Anne

doi:10.1016/j.rdc.2017.04.008

Cited by 35 publications

(30 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, patients with more active RA better respond to treatment [55], as actually observed in our cohort. However, RA is a polygenic disease whose treatment response depends on many factors such as age, sex, psychological factors, disease activity and duration [56,57]. Four major phenotypes of RA synovium have been highlighted: lymphoid, myeloid, low inflammatory and fibroid, each presenting various molecular and cellular heterogeneities that can impact clinical outcome to therapies [58].…”

Section: Discussionmentioning

confidence: 99%

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

et al. 2020

View full text Add to dashboard Cite

Background: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. Methods:In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharidebinding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). Results:We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. Conclusions:This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The classical predictors such as the presence of auto-antibodies [the rheumatoid factor (RF) and the anti-cyclic citrullinated peptide (anti-CCP)], genotypes encoding the shared epitope HLA-DRB1 gene, smoking and/or periodontitis are largely insufficient to foresee the patient response to a biologic [3]. Genetic predictors represent an ongoing field of research and bear the potential to contribute to the development of a precision medicine approach in the management of autoimmune arthropathies [4,5]. Nonetheless, the identification of genetic markers of disease outcome and response to treatment is still at its infancy and has been somewhat disappointing so far [6].…”

mentioning

confidence: 99%

The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis: a case report

Poubelle

Pagé

Longchamps

et al. 2019

Clinical & Translational Med

View full text Add to dashboard Cite

Background Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classical and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treatment selection is still based on a trial-and-error approach. Here, we report a clinical case demonstrating the usefulness of examining the leukocytes’ secretome of patients. We set up and standardized a protocol that examines a patient’s immune responses to establish the secretome of the blood mononuclear leukocytes and personalize the biotherapy. Case presentation A 24-year-old woman was diagnosed with active early rheumatoid arthritis. The initial treatment regimen (prednisone, methotrexate, hydroxychloroquine, naproxen) was inefficient, as well as the anti-TNF adalimumab. The diagnosis was revised as possible rheumatoid arthritis-like psoriatic arthritis and adalimumab was replaced by abatacept (IgG1 Fc-CTLA-4) to no avail. Five years later, abatacept was replaced by the anti-IL-12/IL-23 ustekinumab with no objective control over the symptoms. The patient was thus enrolled in a prospective study based on the quantification of cytokines secreted by peripheral blood leukocytes stimulated with well-known immune activators of pattern recognition receptors and cytokine signalling. The results of this study revealed that plasma concentrations of cytokines were similar between the patient and healthy donors. In comparison to leukocytes from healthy donors, the patient’s secretome showed a unique overproduction of IL-6. The anti-IL-6 receptor tocilizumab was, therefore, administered with a rapid improvement of her active psoriatic arthritis that remained dependent on low prednisone dosage. Clinical parameters progressively returned to normal levels and her quality of life was greatly improved, despite the major delay to begin the present personalized treatment. Conclusions An efficient way to effectively treat patients with complex autoimmune arthropathies, and avoid irreversible disability, is to know their leukocytes’ secretome to identify abnormally secreted cytokines and personalize their biotherapy, as exemplified by this case report.

show abstract

“…RA is not a simple monogenic disease, but a polygenic disease whereby environmental and multiple genetic loci increase the individuals risk of developing disease. Successful application of common polygenic modeling approaches would require sample sizes greater than 1000 individuals for traits with less than 50% heritability [1]. The joint index vector enables us to handle 10,000 or more data and to discriminate patients with high disease activity and poor physical function from others.…”

Section: Discussionmentioning

confidence: 99%

“…The joint index vector enables us to handle 10,000 or more data and to discriminate patients with high disease activity and poor physical function from others. Pharmacogenetic and genomic studies have the potential to enable precision medicine by providing biomarkers to target the right drug to the right patients; however, a large number of studies results to date have been disappointing and have not yielded a change in clinical practice [1]. One of the reasons is a difficulty to capture response in RA.…”

Section: Discussionmentioning

confidence: 99%

“…A number of factors affect the development of RA, and several markers including genetic information have been investigated as potential means of distinguishing patients with preferable outcomes from others; however, confirmed evidence regarding personalized therapy is still limited [1,2]. Recalling the basic fact that joint inflammation is an essential aspect of RA, it is quite natural and reasonable to look closely into which joints are thus affected.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Joint index vector: a novel assessment measure for stratified medicine in patients with rheumatoid arthritis

et al. 2018

View full text Add to dashboard Cite

show abstract

Precision Medicine in Rheumatoid Arthritis

Cited by 35 publications

References 53 publications

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis: a case report

Joint index vector: a novel assessment measure for stratified medicine in patients with rheumatoid arthritis

Contact Info

Product

Resources

About