Association of IL1Β (-511 A/C) and IL6 (-174 G &gt; C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis

Cubino, N.; Montilla, Carlos; Usategui-Martín, Ricardo; Cieza-Borrela, C.; Carranco, T.; Calero-Paniagua, Ismael; Quesada, A. González; Cañete, Juan D.; Queiró, Rubén; Sánchez, María del Carmen González; Hidalgo, Cristina; Martínez, O.; Pino‐Montes, Javier del; Díaz-Álvarez, Agustín; González-Sarmiento, Rogelio

doi:10.1007/s10067-016-3301-2

Cited by 13 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Regarding the association between serum levels of IL-6 and the presence of HLA-B27, indirectly, these results agree with a previous study, where the relationship between the IL-6 polymorphism (-174 G / C) and the presence of HLA-B27, in it, the G allele of the polymorphism, related to an increase in transcriptional activity and secondarily with higher levels of IL-6, was signi cantly associated with negative HLA-B27 [5,17].…”

Section: Discussionsupporting

confidence: 91%

“…Similarly, the decrease in IL-6 levels in synovial uid, after treatment with a TNF-α inhibitor, was associated with a Clinical improvement [4]. On the other hand, the polymorphism of IL-6 (-174 G > C) has been related to the peripheral forms of PsA, so that IL-6 could be related to the clinical form of the disease [5]. Although the role of IL-6 in the comorbidity of other diseases is known, there is not much information in this regard in patients with PsA [6,7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of IL-6 and TNF-α on clinical manifestations, activity and comorbidity in a group of patients with psoriatic arthritis

Montilla

Luis

Toledano

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives To relate the levels of IL-6 and TNF-α in patients with psoriatic arthritis (PsA) with the clinical variants, the disease activity and the presence of comorbidities. Methods Cross-sectional observational study that included 184 patients with PsA according to CASPAR criteria. IL-6 and TNF-α levels were determined. As clinical variables, the clinical form (peripheral, axial or mixed), the presence of dactylitis, the severity of psoriasis measured by PASI and HLA-B27 were determined. Disease activity was measured by the tender joint count, swollen joint count, entheses affected, the severity of psoriasis measured by PASI, ESR, and CRP. The minimum disease activity (MDA) was also measured. Cardiovascular risk markers such as waist /hip ratio (w/ h) and analytical variables: apolipoprotein A, apolipoprotein B, lipoprotein a, insulin, insulin resistance (HOMA-R) and microalbuminuria in urine 24 hours (MA) were included in comorbidity. The presence of fatty liver was measured by ultrasound and fatigue by the FACIT-F questionnaire. Results The mean age of the patients was 55.12 years (SD: 11.29). One hundred and one were men (54.89%). 14.67% of the patients were on treatment with biologic DMARD (bDMARD). One hundred and two patients had peripheral involvement (55.43%), 69 mixed (37.5%) and 13 (7.07%) exclusively axial. 17.93% of the patients had a positive HLA-B27. 53.26% of the patients achieved a MDA. In the analysis of IL-6, we found a correlation with CRP (R: 0.32; P = 0.001), in addition, in patients with positive HLA-B27 we found lower concentrations of IL-6 (3.25 + 2, 26 Vs 5.81 + 7.23) -p < 0.001). We found no association with other variables related to inflammatory activity and / or comorbidity. TNF-α concentrations were higher in patients receiving TNF-α inhibitors ((178.89 SD: 181.31 vs 10.42 SD: 11.15; P < 0.001). Excluding these patients, we only found a correlation with the MA (R: 0.39; p < 0.001). Conclusions In our patients, the presence of HLA-B27 influenced IL-6 concentrations. TNF-α could be considered as a marker of subclinical renal damage.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Influence of IL-6 and TNF-α on clinical manifestations, activity and comorbidity in a group of patients with psoriatic arthritis

Montilla

Luis

Toledano

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Nonetheless, we did not identify any strong candidate variants to explain the phenotype. We also performed Sanger sequencing to analyze specific non-coding polymorphisms in the IL6 promoter and 5′UTR that could potentially account for some of the patient's phenotype since the clinical spectrum of PsoA, more precisely the active peripheral arthritis, has been linked to IL6 (-174G/C) polymorphism [17]. Coding regions as well as flanking 5′ untranslated regions of the IL6 gene (RefSeq: NM_000600.5) were amplified by AmpliTaq Gold Fast PCR Master Mix (Thermo Fisher Scientific Inc., Waltham, Massachusetts, USA) and sequenced on SeqStudio Genetic Analyzer (Applied Biosystems Inc., Foster City, California, USA).…”

Section: Discussionmentioning

confidence: 99%

The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis: a case report

Poubelle

Pagé

Longchamps

et al. 2019

Clinical & Translational Med

View full text Add to dashboard Cite

Background Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classical and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treatment selection is still based on a trial-and-error approach. Here, we report a clinical case demonstrating the usefulness of examining the leukocytes’ secretome of patients. We set up and standardized a protocol that examines a patient’s immune responses to establish the secretome of the blood mononuclear leukocytes and personalize the biotherapy. Case presentation A 24-year-old woman was diagnosed with active early rheumatoid arthritis. The initial treatment regimen (prednisone, methotrexate, hydroxychloroquine, naproxen) was inefficient, as well as the anti-TNF adalimumab. The diagnosis was revised as possible rheumatoid arthritis-like psoriatic arthritis and adalimumab was replaced by abatacept (IgG1 Fc-CTLA-4) to no avail. Five years later, abatacept was replaced by the anti-IL-12/IL-23 ustekinumab with no objective control over the symptoms. The patient was thus enrolled in a prospective study based on the quantification of cytokines secreted by peripheral blood leukocytes stimulated with well-known immune activators of pattern recognition receptors and cytokine signalling. The results of this study revealed that plasma concentrations of cytokines were similar between the patient and healthy donors. In comparison to leukocytes from healthy donors, the patient’s secretome showed a unique overproduction of IL-6. The anti-IL-6 receptor tocilizumab was, therefore, administered with a rapid improvement of her active psoriatic arthritis that remained dependent on low prednisone dosage. Clinical parameters progressively returned to normal levels and her quality of life was greatly improved, despite the major delay to begin the present personalized treatment. Conclusions An efficient way to effectively treat patients with complex autoimmune arthropathies, and avoid irreversible disability, is to know their leukocytes’ secretome to identify abnormally secreted cytokines and personalize their biotherapy, as exemplified by this case report.

show abstract

“…This included infectious diseases such as tuberculosis [44], neurodegenerative diseases such as Alzheimer’s disease [45], autoimmune and autoinflammatory diseases such as psoriasis [46] and diabetes type 2 [47], and the occurrence of tumors such as prostate cancer [48]. …”

Section: Production Of Il-1β Requires Two Distinct Signalsmentioning

confidence: 99%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

322

221

View full text Add to dashboard Cite

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

show abstract

Association of IL1Β (-511 A/C) and IL6 (-174 G > C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis

Cited by 13 publications

References 21 publications

Influence of IL-6 and TNF-α on clinical manifestations, activity and comorbidity in a group of patients with psoriatic arthritis

Influence of IL-6 and TNF-α on clinical manifestations, activity and comorbidity in a group of patients with psoriatic arthritis

The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis: a case report

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Contact Info

Product

Resources

About