The association between serum levels of growth differentiation factor‐15 and rheumatoid arthritis activity

Esalatmanesh, Kamal; Fayyazi, Hamidreza; Esalatmanesh, Roozbeh; Khabbazi, Alireza

doi:10.1111/ijcp.13564

Cited by 8 publications

(7 citation statements)

References 29 publications

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“… 10–12 A study evaluated serum GDF-15 in Iran RA patients, showing that serum GDF-15 may be a biomarker to predict high disease activity. 13 Another study discussed serum GDF-15 in Turkish RA patients, reporting that serum GDF-15 was elevated in RA patients when compared to that in controls. 11 RA patients with active disease activity had higher serum levels of GDF-15 compared to that in patients with less active disease activity, and serum levels of GDF-15 were positively related to ESR levels and DAS28 score.…”

Section: Discussionmentioning

confidence: 99%

Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis

YW¹,

CS²

2022

JIR

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Purpose Rheumatoid arthritis (RA) is an inflammatory rheumatic disease, which has been demonstrated to correlate with mutated genetics. Growth and differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily and is expressed in different organs, tissues and immune cells. To date, limited studies have evaluated plasma levels of GDF-15 in RA patients, and whether GDF-15 gene polymorphisms correlate with RA risk in the Chinese Han population has not been clarified. Patients and Methods This case-control study recruited 910 age- and sex-matched RA patients and healthy controls. Plasma levels of GDF-15 were examined by enzyme linked immunosorbent assay, and polymorphisms (rs1055150, rs1058587, rs3787023, and rs4808793) were genotyped by KASP method. Results RA patients had higher levels of GDF-15 as compared to that in healthy controls. Patients with positive CRP also showed higher levels of GDF-15 when compared to that in patients with negative CRP. Levels of GDF-15 correlated with disease activity score. Frequencies of GG, GC, GG+GC genotypes and G allele in GDF-15 gene rs1058587 were significantly elevated in RA patients compared to controls. Frequencies of CC genotype and C allele in GDF-15 gene rs3787023 were higher in RA patients compared to controls. Other polymorphisms did not correlate with RA susceptibility. Moreover, the four polymorphisms were not correlated with levels of GDF-15. Conclusion Plasma levels of GDF-15 were elevated in RA patients and GDF-15 gene polymorphisms were related to RA risk in the Chinese Han population.

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Section: Discussionmentioning

confidence: 99%

Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis

YW¹,

CS²

2022

JIR

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“…Thus, we cannot offer valid data on the extent of lung water. Furthermore, moderately elevated levels of GDF-15 (usually below 2 ng/ml) can be found in obesity ( 47 ), aging ( 48 ), autoimmune comorbidities ( 49 ) or cardiovascular disease ( 50 ). Levels similar to our COVID-19 patients are limited to conditions like pregnancy ( 51 ), diabetic nephropathy ( 52 ) and advanced cancers ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study

et al. 2020

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Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14 th and May 28 th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.

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“…GDF15 might impact chronic inflammation and autoimmunity. In fact, GDF15 serum levels were shown to be positively correlated with disease activity in rheumatoid arthritis patients [9, 18]. In addition, proteomic analysis has shown an absence of GDF15 in islet cells from individuals with an inflammatory stage of type I diabetes [19].…”

Section: Introductionmentioning

confidence: 99%

GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

et al. 2022

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Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15−/− C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.

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The association between serum levels of growth differentiation factor‐15 and rheumatoid arthritis activity

Cited by 8 publications

References 29 publications

Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis

Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis

Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study

GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

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