Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD?+) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD?+), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T?>?C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

HLA association with the susceptibility to anti-synthetase syndrome.

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD.This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM); SR-M is supported by funds of the RETICS Program [grant number RD16/0012/0009] from the `Instituto de Salud Carlos III´ (ISCIII), co-funded by the European Regional Development Fund (ERDF); BA-M is a recipient of a ‘López Albo’ Post-Residency Programme funded by Servicio Cántabro de Salud; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; LL-G is supported by funds of ISCIII, co-funded by ERDF [grant number PI18/00042]; OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10; EAR is partially supported by Versus Arthritis [grant number 20719] and by Scleroderma and Raynaud's UK [grant number BR11]; RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, ‘Investing in your future’) [grant number CP16/00033]

HLA association with the susceptibility to anti-synthetase syndrome

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD

Influence of MUC5B gene on antisynthetase syndrome

ABSTRACT: MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), co-funded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

A comparative analysis of mental health legislation across Europe

When considering the recent European Court of Human Rights case law, related to judgements having as object the relationship between "Detention and mental health", it is easy to realize how frequently occur human rights violations against people with mental health problems in Europe. Sometimes those violations are justified by political or social views which consider mental problems as an expression of social danger, stigmatizing the pathology and the person who carries that burden. My paper will focus on some aspects of the Belgian and the Swedish legislation and will also formulate some considerations in comparison with the Italian system

Profili di inammissibilità della richiesta di messa alla prova dell’adulto – nota a ordinanza Tribunale di Taranto GIP Rosati, del 22 settembre 2015, imp. Battista

La giurisprudenza è chiamata a risolvere il nodo interpretativo riguardante le conseguenze dell’omessa allegazione, per lo meno, di una richiesta di elaborazione del programma, previamente avanzata dall’interessato al locale U.e.p.e., che – pur non essendo espressamente sanzionata a pena di inammissibilità della istanza di sospensione del processo con messa alla prova – sembra rappresentare condizione indispensabile per la delibazione di quest’ultima da parte del giudice. Il quale, pertanto, come deciso con il provvedimento che si annota – deve pronunciare una decisione di absolutio ab instantia, che equivale ad accertare l’attitudine funzionale negativa della domanda

De jure condendo: Protezione della libertà personale prima del suo sacrificio – Completamento del giusto processo attraverso la separazione delle carriere – Rimodulazione normativa dell’art. 191 c.p.p. e codifica della ‘inutilizzabilità derivata’

- Protezione della libertà personale prima del suo sacrificio (esame e commento della proposta di legge C. 652, recante «Modifiche al codice di procedura penale, in materia di misure cautelari personali», presentata il 29 novembre 2022 d’iniziativa dell’on. Costa); - Completamento del giusto processo attraverso la separazione delle carriere (esame e commento della proposta di legge costituzionale C. 23, recante «Modifiche all’art. 87 ed al Titolo IV della parte II della Costituzione in materia di separazione delle carriere giudicante e requirente della magistratura», presentata il 13 ottobre 2022 dall’on. Costa ed abbinata alle proposte C. 434, C. 806 e C. 824); - Rimodulazione normativa dell’art. 191 c.p.p. e codifica della ‘inutilizzabilità derivata’ (esame e commento della proposta di legge C. 729, d’iniziativa degli on.li Calderone, Patriarca e Pittalis, presentata il 20 dicembre 2022 e recante «Modifiche all'articolo 191 del codice di procedura penale in materia di inutilizzabilità delle prove illegittimamente acquisite»)

Media e processo penale nella giurisprudenza della Corte europea dei diritti dell’uomo

Il contributo si occupa di esaminare i principi convenzionali e la giurisprudenza elaborata dalla Corte europea dei diritti dell'uomo sulla complessa problematica relativa al rapportro tra processo penale e informazione

De jure condendo: Effettività del divieto di utilizzazione delle denunce anonime – Déjà-vècu sul potere di impugnazione delle sentenze di proscioglimento da parte della pubblica accusa – Strategia integrata e multidimensionale per rafforzare gli strumenti di contrasto e prevenzione del fenomeno della violenza nei confronti delle donne e della violenza domestica

Effettività del divieto di utilizzazione delle denunce anonime (proposta di legge C. 3286, recante «Modifiche all’articolo 333 del codice di procedura penale, in materia di divieto di utilizzazione delle denunce anonime», presentata il 17 settembre 2021 d’iniziativa dell’on. Ferraioli). Déjà-vècu sul potere di impugnazione delle sentenze di proscioglimento da parte della pubblica accusa (d.d.l. S. 2499 concernente «Modifiche al codice di procedura penale in materia di impugnazione»). Strategia integrata e multidimensionale per rafforzare gli strumenti di contrasto e prevenzione del fenomeno della violenza nei confronti delle donne e della violenza domestica (d.d.l. S. 2530 recante «Disposizioni per la prevenzione e il contrasto del fenomeno della violenza nei confronti delle donne e della violenza domestica», il quale interviene a breve distanza dalla l. n. 134 del 2021, che, attraverso alcune modifiche di carattere immediatamente precettivo, ha rafforzato la tutela delle vittime di violenza domestica e di genere)