Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis

Winter, L. De; Hansen, Wendy L. J.; Steenbergen, H.W. van; Geusens, Piet; Lenaerts, Jan; Somers, Klaartje; Stinissen, Piet; Mil, Annette H M van der Helm-van; Somers, Veerle

doi:10.1093/rheumatology/kew198

Cited by 26 publications

(16 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is probably due to different patient populations in terms of numbers of patients and ethnicity, and differences in the autoantibody identification approach [ 13 ], amongst other reasons. Nevertheless, all screening approaches result in potential targets for further individual testing and carry the potential for future diagnostic improvements, as has elegantly been demonstrated previously [ 13 , 22 ].…”

Section: Discussionmentioning

confidence: 89%

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis

et al. 2016

View full text Add to dashboard Cite

BackgroundThe aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity.MethodWe incubated 5892 recombinant proteins coupled to fluorescent beads, with patients’ sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought.ResultScreening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2).ConclusionsComprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

show abstract

Section: Discussionmentioning

confidence: 89%

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Novel autoantibodies in RA were previously identified by serological antigen selection (SAS) [50] and recently validated in two large independent study populations [51]. Antibodies to two Hasselt University (UH) peptides, UH-RA.1 and UH-RA.21, were most promising as they were found in up to one-third of early RA patients.…”

Section: Ra: a Heterogeneous Disease Based On Serological Markersmentioning

confidence: 99%

cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is the world's most common autoimmune disease mainly characterized by a chronic inflammation of multiple synovial joints. Rheumatologists now have a whole range of treatment options including glucocorticoids (GCs), classical synthetic and biological disease-modifying antirheumatic drugs (cs- and bDMARDS), resulting in a tremendous improvement in treatment outcomes for RA patients over the last two decades. Despite this progress, the choice of treatment regimen to achieve stable remission at the individual patient level still largely depends on trial and error. In this review, the need for novel theranostic markers that can predict a patient's response to methotrexate, the standard first-line csDMARD treatment, is discussed. Like in many autoimmune diseases, the majority of RA patients form a whole range of autoantibodies. We aim to find novel theranostic autoantibody markers using serological antigen selection, a high-throughput technique that uses cDNA phage display to identify novel antigen targets. We have constructed a barcoded cDNA phage display library from the synovial tissue of three RA patients by fusing cDNA products to the filamentous phage minor coat protein VI. This library contains a large proportion of full-length genes and gene fragments that are cloned in frame with the phage gene VI. By screening this library for antibody reactivity in serum samples of patients from the CareRA trial, which compared different intensive treatment strategies based on csDMARDs and a step-down GC schedule, our cDNA phage display library has great potential for the discovery of novel theranostic autoantibody biomarkers.

show abstract

“…However, early RA especially serum RF and anti-CCP antibody-negative is di cult to diagnose due to the lack of effective biomarkers. Although studies have reported that some biomarkers, such as 14-3-3η autoantibodies and calprotectin, may be effective in the diagnosis of early RA, they have not been used in its clinical diagnosis [4][5][6][7]. Therefore, it is vital to identify new and effective biomarkers for the early diagnosis and treatment of RA.…”

Section: Introductionmentioning

confidence: 99%

Three hematologic/immune system-specific expressed genes are considered as the potential biomarkers for the diagnosis of early rheumatoid arthritis through bioinformatics analysis

Cheng

2020

Preprint

View full text Add to dashboard Cite

Background Rheumatoid arthritis (RA) is the most common chronic autoimmune connective tissue disease. However, early RA is difficult to diagnose due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses.Methods Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein-protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student’s t-test.Results A total of 275 DEGs, including 197 downregulated genes and 78 upregulated genes, were identified between the samples from RA and OA. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and 4 gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets, and three genes (granzyme A (GZMA), protein regulator of cytokinesis 1 (PRC1), and threonine/tyrosine kinase protein kinase (TTK)) that have a high diagnostic value for early RA were identified. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA.Conclusions This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.

show abstract

Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis

Abstract: This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA.

Cited by 26 publications

References 16 publications

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis

cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid arthritis

Three hematologic/immune system-specific expressed genes are considered as the potential biomarkers for the diagnosis of early rheumatoid arthritis through bioinformatics analysis

Contact Info

Product

Resources

About