Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

Tuckwell, Katie; Gabay, Cem; Sornasse, Thierry; Laubender, Ruediger Paul; Wang, Jianmei; Townsend, Michael J.

doi:10.1186/s42358-019-0097-1

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…sICAM-1 is usually expressed at low levels in vascular endothelial cells, lamina propria of the intestinal mucosa, and mononuclear macrophages in lymph nodes in normal intestinal tissue. In IBD intestinal tissue, the expression and distribution of sICAM-1 are significantly increased and are closely related to the degree of tissue inflammation ( 33 , 34 ). Therefore, detection of serum sICAM-1 level may become an important indicator for monitoring the functional status of intestinal mucosal ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Tang

Zhu

et al. 2022

Front. Med.

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BackgroundImmunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.MethodsThirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.ResultsIn patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932–1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.ConclusionThe urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

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Section: Discussionmentioning

confidence: 99%

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Tang

Zhu

et al. 2022

Front. Med.

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“…Of several serum biomarkers studies, the ratio of soluble intercellular adhesion molecule 1 (sICAM1) to C-X-C motif chemokine 13 (CXCL13), proposed as a serum correlate of myeloid versus lymphoid dominant synovial pathology respectively, differentiated response to therapy in a phase 4 trial biomarker sub-study; high sICAM:CXCL13 ratio predicted response to anti-TNF therapy, whilst the reverse predicted response to anti-IL6R [39]. This however has not been reproduced in other studies [40].…”

Section: Serological Status and Other Serum Biomarkersmentioning

confidence: 98%

Understanding Refractory Rheumatoid Arthritis: Implications for a Therapeutic Approach

Melville

Kearsley‐Fleet

Buch

et al. 2020

Drugs

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Refractory RA has emerged as an area of unmet need in a landscape of generally well-controlled disease. Whilst most patients are adequately treated on methotrexate and other first-line diseasemodifying anti-rheumatic drugs (DMARDs), a proportion requires biologic (b) and targeted synthetic (ts) DMARDs, with a further subsection failing multiple agents. Recent observational studies have adopted working definitions of refractory RA based on number of failed DMARDs, with prevalence estimates of 6 -21% depending on threshold and study population. Risk factors include treatment delay, baseline disease activity and function, female gender, smoking, obesity and lower socioeconomic status. Practical and conceptual challenges in defining refractory RA arise from limitations of disease activity scores used to assess response, with attendant misclassification risk of co-existent non-inflammatory pathology, and failure to capture additional outcomes, such as fatigue, that have variable treatment response. Time is an important factor in defining refractory disease; registry studies show that growing treatment options have resulted in rapid b/tsDMARD cycling and earlier refractory status, and refractory RA is itself a dynamic concept, evolving with each new therapeutic class. Whilst the biology underpinning refractory RA remains largely unknown, a general overview of biomarker studies and clinical trials old and new offers insights into prediction of response and treatment failure. Whilst the future holds promise, current data is insufficient to personalise or meaningfully sequence b/tsDMARDs. Therefore, avoidance of a refractory course is best achieved by following proven management paradigms (e.g. early diagnosis and treat-to-target), addressing modifiable risk factors, and considering enrolment in novel trials. Rheumatoid arthritis (RA) is a common autoimmune disease affecting 1% of the adult population. Whilst many patients are adequately treated with methotrexate and other conventional synthetic (cs) disease modifying anti-rheumatic drugs (DMARDs), an estimated two-fifths of patients do not respond to methotrexate and many will go on to require a biologic (b) or targeted synthetic (ts) DMARD. For most patients, b/ts DMARDs offer the real opportunity for disease remission, but for a small but not insignificant proportion, disease control remains elusive despite trials of multiple different b/ts DMARDs. This review discusses the concept of refractory RA and our current understanding of this potentially unmet need in rheumatology. Key Points:• Despite tremendous progress in the treatment of rheumatoid arthritis (RA) over the past two decades in the era of targeted therapies, refractory disease has emerged as an area of unmet clinical need. • There is currently no universally accepted definition of refractory RA, but various working definitions based on number of failed DMARDs have permitted initial insights into the scale of the problem and risk factors for a refractory disease course.• A detailed mechanistic understanding o...

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“…A major limitation is the necessity for multiple biomarkers to accurately apply RA therapy. Predicting the efficacy of different therapies for RA based on the heterogeneity of synovial tissue is a promising direction for future research (64,71,73,74).…”

Section: Class II Hla Genesmentioning

confidence: 99%

Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

et al. 2021

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Rheumatoid arthritis is an autoimmune disease that exhibits significant clinical heterogeneity. There are various treatments for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and inflammatory cytokine inhibitors (ICI), typically associated with differentiated clinical effects and characteristics. Personalized responsiveness is observed to the standard treatment due to the pathophysiological heterogeneity in rheumatoid arthritis, resulting in an overall poor prognosis. Understanding the role of individual variation in cellular and molecular mechanisms related to rheumatoid arthritis will considerably improve clinical care and patient outcomes. In this review, we discuss the source of pathophysiological heterogeneity derived from genetic, molecular, and cellular heterogeneity and their possible impact on precision medicine and personalized treatment of rheumatoid arthritis. We provide emphasized description of the heterogeneity derived from mast cells, monocyte cell, macrophage fibroblast-like synoviocytes and, interactions within immune cells and with inflammatory cytokines, as well as the potential as a new therapeutic target to develop a novel treatment approach. Finally, we summarize the latest clinical trials of treatment options for rheumatoid arthritis and provide a suggestive framework for implementing preclinical and clinical experimental results into clinical practice.

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Levels of CXCL13 and sICAM-1 correlate with disease activity score in patients with rheumatoid arthritis treated with tocilizumab

Cited by 10 publications

References 12 publications

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Understanding Refractory Rheumatoid Arthritis: Implications for a Therapeutic Approach

Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

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