Strong association between myotonic dystrophy type 2 and autoimmune diseases

Tieleman, A.A.; Broeder, Alfons A den; Logt, A. van de; Engelen, B.G.M. van

doi:10.1136/jnnp.2008.156562

Cited by 39 publications

(38 citation statements)

References 19 publications

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“…As described previously, it has also been implicated in immune disorders (1,15–19). Therefore, we investigated whether CNBP may act as a transcriptional regulator in the immune response using a DNA–protein complex pull-down assay.…”

Section: Resultsmentioning

confidence: 53%

“…It is mainly localized to both the nuclei and cytoplasm of cells in mammals, amphibians, chickens and fish (10–14). In particular, several studies have shown that CNBP-mediated DM2 pathogenesis may confer susceptibility to several immune-related diseases, such as rheumatoid arthritis and inflammatory eosinophilic infiltration (15,16). Additionally, hyperactivation of the innate immune response is associated with the pathology of DM (17).…”

Section: Introductionmentioning

confidence: 99%

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CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Lee

Kim

et al. 2017

Nucleic Acids Research

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The transcription of inflammatory genes is an essential step in host defense activation. Here, we show that cellular nucleic acid-binding protein (CNBP) acts as a transcription regulator that is required for activating the innate immune response. We identified specific CNBP-binding motifs present in the promoter region of sustained inflammatory cytokines, thus, directly inducing the expression of target genes. In particular, lipopolysaccharide (LPS) induced cnbp expression through an NF-κB-dependent manner and a positive autoregulatory mechanism, which enables prolonged il-6 gene expression. This event depends strictly on LPS-induced CNBP nuclear translocation through phosphorylation-mediated dimerization. Consequently, cnbp-depleted zebrafish are highly susceptible to Shigella flexneri infection in vivo. Collectively, these observations identify CNBP as a key transcriptional regulator required for activating and maintaining the immune response.

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Section: Resultsmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Lee

Kim

et al. 2017

Nucleic Acids Research

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“…3, 14 In addition, a strong association between Dutch DM2 patients and autoimmune diseases or autoantibody production was recently reported, in contrast with those with DM1 whose data were comparable with the general population. 15 Interestingly, all three patients in the present study were asthmatic, yet this association has not been previously described in the literature. To examine whether it is a true association or a mere coincidence, more families with different genetic backgrounds should be investigated.…”

Section: Discussionmentioning

confidence: 45%

Clinical and genetic analysis of the first known Asian family with myotonic dystrophy type 2

et al. 2014

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Myotonic dystrophy type 2 (DM2) is more common than DM1 in Europe and is considered a rare cause of myotonic dystrophies in Asia. Its clinical course is also milder with more phenotypic variability than DM1. We herein describe the first known Asian family (three affected siblings) with DM2 based on clinical and genetic analyses. Notably, two of the affected siblings were previously diagnosed with limb-girdle muscular dystrophy. Myotonia (the inability of the muscle to relax) was absent or only faintly present in these individuals. The third sibling had grip myotonia and is the first known Asian DM2 patient. The three DM2 siblings share several systemic characteristics, including late-onset, proximal-dominant muscle weakness, diabetes, cataracts and asthma. Repeat-primed PCR across the DM2 repeat revealed a characteristic ladder pattern of a CCTG expansion in all siblings. Southern blotting analysis identified the presence of 3400 repeats. Further DM2 studies in Asian populations are needed to define the clinical presentation of Asian DM2 and as yet unidentified phenotypic differences from Caucasian patients.

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“…(9) Day et al reported that although DM2 patients have normal IgA levels, 65% have low IgG levels and 11% have low IgM levels. (3) Similarly, 17 of the present DM2 patients had normal IgA levels, 12 of 16 [75%] had low IgG levels, and 2 of 17 [12%] had low IgM levels.…”

Section: Resultsmentioning

confidence: 99%

“…Compared with patients with DM1, age and sex matched DM2 patients may have a higher frequency of autoimmune disorders. (9) It is also possible that IgG has an accelerated turnover rate in DM2 and that IgG is selectively impaired (or sequestered) via a RNA mediated process. (12) If this is the case, IgG may have a role as a serum biomarker during clinical trials of agents (such as morpholino antisense oligonucleotides) which may alter the toxic burden of RNA (13) while simultaneously modifying IgG counts.…”

Section: Commentmentioning

confidence: 99%

Laboratory Abnormalities in Patients With Myotonic Dystrophy Type 2

et al. 2011

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Background: Myotonic dystrophy type 2 (DM2) is a recently discovered adult muscular dystrophy. Similar to DM1, this disease causes progressive debilitating weakness, clinical myotonia, and early cataracts and is thought to cause widespread physiologic dysfunction of multiple organ systems. Objective: To analyze and compile the laboratory abnormalities of patients with DM2. Design: Baseline DM2 laboratory data were compiled representing 68 different types of laboratory tests and 1442 total studies. Setting: University medical center. Patients: Eighty-three adults with genetically confirmed or clinically probable DM2 were identified. Of these patients, 49 had documented baseline laboratory screening. Main Outcome Measures: The individual frequencies of abnormal laboratory values in the population with DM2 studied.Results: Of the 1442 studies, results for 359 (24.9%) were outside of their standard reference ranges. Of the 68 types of laboratory tests studied, 43 had values from 15 or more different patients with DM2. The relative frequency of an abnormally elevated laboratory value was greater than 50% in several tests, including the levels of creatine kinase, total cholesterol, lactate dehydrogenase, and alanine aminotransferase. In addition, serum levels of IgG were low in 75% of all patients with DM2 tested, and absolute lymphocyte counts were low in 54% of all patients with DM2 tested. Conclusions:There is a high frequency of laboratory abnormalities in patients with DM2. These abnormalities provide insight into the widespread pathologic manifestations of DM2 and may form a basis for clinical monitoring and disease screening.

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Strong association between myotonic dystrophy type 2 and autoimmune diseases

Abstract: The results provide new insight into the clinical picture of DM2. In addition, possible explanations for the association between DM2 and autoimmune diseases are proposed.

Cited by 39 publications

References 19 publications

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Clinical and genetic analysis of the first known Asian family with myotonic dystrophy type 2

Laboratory Abnormalities in Patients With Myotonic Dystrophy Type 2

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