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Mixed connective tissue disease: state of the art on clinical practice guidelines.

ABSTRACT: Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. Since no specific CPGs on MCTD were found, other CPGs developed for other CTDs were taken into consideration in order to discuss what can be applied to MCTD even if designed for other diseases. Three major objectives were proposed for the future development of CPGs: MCTD diagnosis (diagnostic criteria), MCTD initial and follow-up evaluations, MCTD treatment. Early diagnosis, epidemiological data, assessment of burden of disease and QOL aspects are among the unmet needs identified by patients.

SUBMITTER: Benjamin C

PROVIDER: S-EPMC6203102 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Mixed connective tissue disease: state of the art on clinical practice guidelines.

Chaigne Benjamin B Scirè Carlo Alberto CA Talarico Rosaria R Alexander Tobias T Amoura Zahir Z Avcin Tadej T Beretta Lorenzo L Doria Andrea A Guffroy Aurelien A Guimarães Vera V Hachulla Éric É Krieg Thomas T Launay David D Lepri Gemma G Moinzadeh Pia P Müller-Ladner Ulf U Rednic Simona S Rodrigues Ana A Tas Sander W SW van Vollenhoven Ronald F RF Vieira Ana A Bombardieri Stefano S Fonseca João Eurico JE Galetti Ilaria I Schneider Matthias M Smith Vanessa V Cutolo Maurizio M Mosca Marta M Fischer-Betz Rebecca R

RMD open 20181018 Suppl 1

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Mu ...[more]

PMID: 30402271

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Project description:Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.

Project description:BackgroundMixed connective tissue disease (MCTD) is a rare condition that is distinguished by the presence of specific U1-RNP antibodies. Information about its etiopathology and diagnostics is still unclear. miRNAs such as miR-146, miR-155, and miR-143 emerged as key regulators of the immune system, known to be involved in the development of autoimmune diseases and cancers. We performed an association study between immune-related miRNAs and MCTD severity and susceptibility.MethodsA total of 169 MCTD patients and 575 healthy subjects were recruited to the case-control study. The miRNA polymorphisms were genotyped using TaqMan SNP genotyping assay. TNF-?, IL-6, and IFN-? levels in serum were determined using ELISA. qRT-PCR of TRAF6, IRAK1, and microRNAs was performed using Taqman miRNA assays and TaqMan Gene Expression Assays.ResultsmiR-146a rs2910164 G allele and GG genotype as well as miR-143 rs713147 A allele were more frequent in healthy subjects than in MCTD patients. miR-146a rs2910164 CC genotype and miR-143 T-rs353299*T-rs353291*T-rs713147*G-rs353298 and C-rs353299*C-rs353291*T-rs713147*A-rs353298 haplotypes were associated with MCTD susceptibility. miR-146a rs2910164 C/T was associated with scleroderma and lymphadenopathy. miR-143 rs353299 C/T was associated with swollen fingers or hands, the presence of enlarged lymph nodes, and pericarditis/pleuritis. miR-143 rs353298 A/G was associated with the occurrence of pericarditis/pleuritis and scleroderma. miR-143 rs353291 T/C showed association with pericarditis/pleuritis. The serum TNF-?, IFN-?, and IL-6 levels were significantly higher in MCTD patients compared to healthy subjects. miR-143 SNPs were associated with higher proinflammatory cytokine concentration in serum only in healthy controls. IRAK1 and TRAF6 expression were higher in the MCTD patients compared to controls.ConclusionsThe results of our case-control study indicate the possible significance of miR-146a and miR-143/145 in the susceptibility and clinical picture of MCTD.

Project description:The molecular diagnosis of Y-chromosomal microdeletions is a common routine genetic test which is part of the diagnostic workup of azoospermic and severe oligozoospermic men. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) have been actively involved in supporting the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 2004 laboratory guidelines summarizes all the clinical novelties related to the Y chromosome (classic, partial and gene-specific deletions, genotype-phenotype correlations, methodological issues) and provides an update on the results of the quality control programme. These aspects also reflect the consensus of a large group of specialists present at a round table session during the recent Florence-Utah-Symposium on 'Genetics of male infertility' (Florence, 19-21 September, 2013). During the last 10 years the gr/gr deletion has been demonstrated as a significant risk factor for impaired sperm production. However, the screening for this deletion type in the routine diagnostic setting is still a debated issue among experts. The original basic protocol based on two multiplex polymerase chain reactions remains fully valid and appropriate for accurate diagnosis of complete AZF deletions and it requires only a minor modification in populations with a specific Y chromosome background. However, in light of novel data on genotype-phenotype correlations, the extension analysis for the AZFa and AZFb deletions is now routinely recommended. Novel methods and kits with excessively high number of markers do not improve the sensitivity of the test, may even complicate the interpretation of the results and are not recommended. Annual participation in an external quality control programme is strongly encouraged. The 12-year experience with the EMQN/EAA scheme has shown a steep decline in diagnostic (genotyping) error rate and a simultaneous improvement on reporting practice.

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Mixed connective tissue disease: state of the art on clinical practice guidelines.

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Mixed connective tissue disease: state of the art on clinical practice guidelines.

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