14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

Maksymowych, Walter P.; Boire, Gilles; Schaardenburg, Dirkjan van; Wichuk, Stephanie; Türk, S.; Boers, Maarten; Siminovitch, Katherine A.; Bykerk, Vivian P.; Keystone, Ed; Tak, Paul P.; Kuijk, Arno W R van; Landewé, Robert; Heijde, Desirée van der; Murphy, Madeline; Marotta, A.

doi:10.3899/jrheum.141385

Cited by 34 publications

(26 citation statements)

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“…The prevalence of 14-3-3η positivity in children with PJIA RF + was similar to that in another study on early undifferentiated polyarthritis in adults. However, in both early and established RA, a higher prevalence of 14-3-3η (68%) was reported compared to our pediatric population [17,18]. In a previous report, 14-3-3η was positive in 21% of patients with early RA who were seronegative for RF and CCP antibodies, and in 67% of patients with seronegative established RA and in a pediatric study, 31% of PJIA RF-patients had positive 14-3-3η levels [15,19].…”

Section: Discussioncontrasting

confidence: 63%

Prevalence and Significance of Serum 14-3-3η(eta) in Juvenile Idiopathic Arthritis

Reyhan

Zhukov

Lagier

et al. 2020

Preprint

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Background Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA.Methods JIA patients (n = 152) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 20), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels ≥ 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71).Results Elevated 14-3-3η levels were detected in 35/152 (23%) patients, and across all groups tested. Most patients with 14-3-3η had titers ≥ 4 times above the cutoff value. The majority (23, 67%) of 14-3-3η-positive patients were also positive for RF or CCP antibodies, 17 (49%) were positive for all 3, and 12 (8%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF + patients (49%), followed by OJIA (22%). Positivity for 14-3-3η was not significantly associated with disease activity or age at diagnosis.Conclusion Serum 14-3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3η does not appear to correlate with disease activity in JIA.

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Section: Discussioncontrasting

confidence: 63%

Prevalence and Significance of Serum 14-3-3η(eta) in Juvenile Idiopathic Arthritis

Reyhan

Zhukov

Lagier

et al. 2020

Preprint

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“…Patients with colon, ovarian, breast and lung cancer as well as patients with SLE have been found to produce autoantibodies against the c-Myb protein (40). Both categories of patients generate autoantibodies against cyclin-B1, survivin, p16, 14-3-3 proteins, eukaryotic translation initiation factor 4G (eIF-4G) and RAF1 (14,27,28,(34)(35)(36)(40)(41)(42)(43)(44)(45)(46)(47)(48). Autoantibodies against the cyclic citrullinated peptide (CCP) were detected in patients with Sjogren's syndrome and psoriatic arthritis (51, 52) as well as in lymphoma patients (49).…”

Section: Immune Response To Self Antigens In Cancer Patients Partly Cmentioning

confidence: 99%

The crossroads between cancer immunity and autoimmunity antibodies to self antigens

et al. 2017

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The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments. Tregs dysfunction has been observed in patients with paraneoplastic syndromes and/or with autoimmune diseases, while the increase of Tregs has been associated with poor cancer patients prognosis. Novel therapies have employed antibodies against Tregs immune-checkpoint receptors with the aim to boost immune response in cancer patients. The presence of autoantibodies to tumors antigens has also been investigated as a marker for cancer detection and cancer patients prognosis. This report reviews the current knowledge on the analysis and meaning of autoantibodies to self antigens detected in cancer and autoimmune disease patients.

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“…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

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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.

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14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

Abstract: 14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.

Cited by 34 publications

References 20 publications

Prevalence and Significance of Serum 14-3-3η(eta) in Juvenile Idiopathic Arthritis

Prevalence and Significance of Serum 14-3-3η(eta) in Juvenile Idiopathic Arthritis

The crossroads between cancer immunity and autoimmunity antibodies to self antigens

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

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