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    "titulo" => "Growth factors&#58; Do they play a role in entheseal involvement in psoriatic arthritis and undifferentiated spondyloarthritis patients&#63;"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The role of growth factors &#40;GFs&#41; in arthritis is rarely investigated&#44; reporting controversial results&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; the serum levels of IGF-1&#44; FGF-1&#44; TGF&#946; in patients &#40;pts&#41; with undifferentiated spondyloarthritis &#40;SpA&#41; or psoriatic arthritis &#40;PsA&#41; have never been described in literature&#46; Partsch et al&#46; described a higher titer of GH in the sera of PsA pts compared to psoriatic pts&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We describe a study designed to evaluate the serum levels of GFs&#44; IGF-1&#44; FGF-1&#44; GH and TGF&#946;&#44; in PsA pts and SpA pts&#44; with particular focus on the entheseal involvement&#46; Our goal was to assess any differences in the concentration of these GFs between pts with different clinical and instrumental features&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Preliminary data were obtained on 15 pts &#40;all female&#41;&#58; 6 with a new diagnosis of PsA&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> 9 with a new diagnosis of SpA&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> The control group was formed by 5 age-matched healthy females &#40;HC&#41;&#46; The exclusion criteria were intestinal bowel disease&#44; diabetes mellitus&#44; body mass index &#62;30&#44; systemic hypertension&#44; dyslipidemia&#44; alteration of thyroid function&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Serum levels of IGF-1&#44; FGF-1&#44; GH and TGF&#946; were measured using enzyme-linked immunosorbent assay &#40;ELISA&#41;&#46; Moreover&#44; an imaging evaluation was conducted on all pts&#58; the presence of calcific enthesopathy &#40;CE&#41; was assessed using standard radiology&#59; the ultrasound evaluation was conducted according to the Madrid Sonographic Enthesis Index &#40;MASEI&#41; score&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> Disease activity was assessed by means of Disease Activity Score &#40;DAS28&#41;&#44; Disease Activity in PSoriatic Arthritis &#40;DAPSA&#41; and Leeds Enthesitis Index &#40;LEI&#41;&#46; Comparisons between groups were made with one-way analysis of variance &#40;ANOVA&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">We found that serum levels of IGF-1 and TGF&#946; were remarkably but not significantly higher in SpA pts compared to PsA pts and HC&#46; In particular&#44; there was a tendency toward higher serum concentrations of TGF&#946; in pts with CE compared to those pts without and HC &#40;1003&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>208&#46;5 vs&#46; 999&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>156&#46;9 vs&#46; 975&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>61&#46;7&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;965&#41;&#46; Furthermore&#44; a statistically significant negative correlation between TGF&#946; levels and symptoms duration both in SpA and PsA pts was observed &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;582&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;029&#41;&#46; In addition&#44; subjects with moderate &#40;MA&#41; or high disease activity &#40;HA&#41; according to DAPSA score showed a tendency toward higher GH &#40;low activity &#40;LA&#41;&#58; 310&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>449&#46;4&#44; MA&#58; 533&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>967&#46;4&#44; HA&#58; 630<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1074&#46;4&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;903&#41; and IGF-1 &#40;LA&#58; 389&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>532&#46;8&#44; MA&#58; 467&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>825&#46;2&#44; HA&#58; 491&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>585&#46;6&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;908&#41; levels&#44; while TGF&#946; levels were higher only in DAPSA HA &#40;LA&#58; 954&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>257&#46;3&#44; MA&#58; 910&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>170&#46;5&#44; HA&#58; 1049&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>44&#46;1&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;653&#41;&#46; Interestingly&#44; this tendency was not observed when assessing the disease activity using the DAS28 score&#44; except for the HA group &#40;LA&#58; 954&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>257&#46;3&#44; MA&#58; 903&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>207&#46;7&#44; HA&#58; 974&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>124&#46;2&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;91&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The differences we found were not statistically significant most presumably given the small sample size&#46; Since no statistically significant differences in age and BMI were observed between the groups&#44; a difference in the GFs concentration due to physiological hormonal variations can be excluded&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The evidences about DAS28 may be owed to the focus of this score on joint involvement&#44; while enthesitis is not evaluated&#44; as in DAPSA&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The most remarkable result is the significant higher TGF&#946; serum levels in pts with shorter symptoms duration&#44; suggestive for a potential role of TGF&#946; as an early biomarker of disease&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This preliminary study&#44; although lacking statistically significant results&#44; support the hypothesis of an important role played by GFs IGF-1&#44; GH and TGF&#946; rather in the pathogenesis of enthesitis than of joint inflammation&#46; In particular&#44; TGF&#946; should have a key role in earlier phases of SpA and PsA&#46; Further studies&#44; with a larger sample size&#44; are necessary to clarify the role of GFs in the pathogenesis of enthesopathy&#44; and more broadly of spondylarthritis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">No funding was received for this study&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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Vol. 17. Issue 6.
Pages 369-370 (June - July 2021)
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Vol. 17. Issue 6.
Pages 369-370 (June - July 2021)
Letter to the Editor
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Growth factors: Do they play a role in entheseal involvement in psoriatic arthritis and undifferentiated spondyloarthritis patients?
Factores de crecimiento: ¿desempeñan un papel en el compromiso enteseal en pacientes de artritis psoriásica y espondiloartritis indiferenciada?
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Cinzia Rotondo, Daniela Cici
Corresponding author
daniela.cici@gmail.com

Corresponding author.
, Francesco Paolo Cantatore
Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, Ospedali Riuniti Foggia, Viale Pinto 1, 71121 Foggia, Italy
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Table 1. Comparison of demographic, clinical characteristics and serum levels of growth factors between groups in study.
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Dear Editor:

The role of growth factors (GFs) in arthritis is rarely investigated, reporting controversial results.1–4

To the best of our knowledge, the serum levels of IGF-1, FGF-1, TGFβ in patients (pts) with undifferentiated spondyloarthritis (SpA) or psoriatic arthritis (PsA) have never been described in literature. Partsch et al. described a higher titer of GH in the sera of PsA pts compared to psoriatic pts.1

We describe a study designed to evaluate the serum levels of GFs, IGF-1, FGF-1, GH and TGFβ, in PsA pts and SpA pts, with particular focus on the entheseal involvement. Our goal was to assess any differences in the concentration of these GFs between pts with different clinical and instrumental features.

Preliminary data were obtained on 15 pts (all female): 6 with a new diagnosis of PsA,5 9 with a new diagnosis of SpA.6 The control group was formed by 5 age-matched healthy females (HC). The exclusion criteria were intestinal bowel disease, diabetes mellitus, body mass index >30, systemic hypertension, dyslipidemia, alteration of thyroid function.

Serum levels of IGF-1, FGF-1, GH and TGFβ were measured using enzyme-linked immunosorbent assay (ELISA). Moreover, an imaging evaluation was conducted on all pts: the presence of calcific enthesopathy (CE) was assessed using standard radiology; the ultrasound evaluation was conducted according to the Madrid Sonographic Enthesis Index (MASEI) score.7 Disease activity was assessed by means of Disease Activity Score (DAS28), Disease Activity in PSoriatic Arthritis (DAPSA) and Leeds Enthesitis Index (LEI). Comparisons between groups were made with one-way analysis of variance (ANOVA) (Table 1).

Table 1.

Comparison of demographic, clinical characteristics and serum levels of growth factors between groups in study.

Variables  PsA  SpA  HC  P 
Age  49.1±15.7  43.8±12.3  43.2±13.1  .691 
BMI  24.1±3.2  24.2±1.54  22.5±3.6  .233 
Symptoms duration  4.6±3.2  4.00±2.0    .424 
ESR  16±17.7  19.4±14.6    .688 
CRP  0.1±0.2  0.2±0.2    .813 
LEI  3.5±1.2  2.3±1.3    .109 
DAS28  3.2±0.5  2.6±1.1    .287 
DAPSA  24.1±5.7  20.7±6.1    .305 
MASEI  6.5±5.6  5.3±4.5    .665 
SHARP score  33.3±39.7  50.7±33.9    .474 
PARS  4.6±1.1  6.5±8.2    .708 
IGF-1  378.3±330.8  859.4±923.4  366.5±280.6  .638 
FGF-1  9.6±23.5  13.3±22.5  3.5±7.1  .242 
GH  336.1±694.0  991.2±1082.6  593.1±601.6  .679 
TGFβ  968.8±189  1024.3±193.3  927.2±121.1  .464 

Data are expressed as mean±standard deviation; significant P value was set to ≤ .05.

BMI: BODY MASS INdex; CRP: C Reactive Protein; DAPSA: Disease Activity in PSoriatic Arthritis; DAS28: Disease Activity Score; ESR: Erythrocytes Sedimentation Rate; HC: Healthy Controls; LEI: Leeds Enthesitis Index; MASEI: MAdrid Sonographic Enthesitis Index; PARS: Psoriatic Arthritis Ratingen Score; PsA: Psoriatic Arthritis; SpA: undifferentiated Spondyloarthritis.

We found that serum levels of IGF-1 and TGFβ were remarkably but not significantly higher in SpA pts compared to PsA pts and HC. In particular, there was a tendency toward higher serum concentrations of TGFβ in pts with CE compared to those pts without and HC (1003.5±208.5 vs. 999.5±156.9 vs. 975.9±61.7; P=.965). Furthermore, a statistically significant negative correlation between TGFβ levels and symptoms duration both in SpA and PsA pts was observed (r2=0.582; P=.029). In addition, subjects with moderate (MA) or high disease activity (HA) according to DAPSA score showed a tendency toward higher GH (low activity (LA): 310.8±449.4, MA: 533.8±967.4, HA: 630±1074.4; P=.903) and IGF-1 (LA: 389.4±532.8, MA: 467.7±825.2, HA: 491.7±585.6; P=.908) levels, while TGFβ levels were higher only in DAPSA HA (LA: 954.6±257.3, MA: 910.1±170.5, HA: 1049.5±44.1; P=.653). Interestingly, this tendency was not observed when assessing the disease activity using the DAS28 score, except for the HA group (LA: 954.6±257.3, MA: 903.8±207.7, HA: 974.5±124.2; P=.91).

The differences we found were not statistically significant most presumably given the small sample size. Since no statistically significant differences in age and BMI were observed between the groups, a difference in the GFs concentration due to physiological hormonal variations can be excluded.8,9

The evidences about DAS28 may be owed to the focus of this score on joint involvement, while enthesitis is not evaluated, as in DAPSA.

The most remarkable result is the significant higher TGFβ serum levels in pts with shorter symptoms duration, suggestive for a potential role of TGFβ as an early biomarker of disease.

This preliminary study, although lacking statistically significant results, support the hypothesis of an important role played by GFs IGF-1, GH and TGFβ rather in the pathogenesis of enthesitis than of joint inflammation. In particular, TGFβ should have a key role in earlier phases of SpA and PsA. Further studies, with a larger sample size, are necessary to clarify the role of GFs in the pathogenesis of enthesopathy, and more broadly of spondylarthritis.

Funding

No funding was received for this study.

Conflict of interest

None.

Acknowledgements

We would like to thank Prof. Addolorata Corrado and Dr. Giovanni Bellantuono for their contribution in this study.

References
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G. Partsch, C. Schwarzer, A. Dunky, F. Mayer, F. Gschnait, J. Neumüller, et al.
Determination of growth hormone in plasma of psoriatic arthritis, psoriasis vulgaris and seronegative spondylarthritis.
Z Rheumatol, 44 (1985), pp. 267-269
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C.W. Denko, B. Boja, R.W. Moskowitz.
Growth factors, insulin-like growth factor-1 and growth hormone, in synovial fluid and serum of patients with rheumatic disorders.
Osteoarthritis Cartilage, 4 (1996), pp. 245-249
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Insulin-like growth factor I does not drive new bone formation in experimental arthritis.
PLoS ONE, 11 (2016), pp. e0163632
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Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases.
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Copyright © 2020. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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