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PloS One Mar 2010Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous...
Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt) mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66%) beta-myosin heavy chain (beta-MHC, 95%) and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%), all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.
Topics: Animals; Atrial Natriuretic Factor; Carrier Proteins; Cytoskeletal Proteins; Desmin; Dystonia Musculorum Deformans; Dystonin; Heart; Intermediate Filaments; Mice; Microtubules; Myocardial Contraction; Myocardium; Myosin Heavy Chains; Nerve Tissue Proteins; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 20209123
DOI: 10.1371/journal.pone.0009465 -
Journal of Alzheimer's Disease : JAD 2018Recent studies have shown an epidemiological and immunological association between bullous pemphigoid (BP) and several neurological or psychiatric diseases. Here, our...
Recent studies have shown an epidemiological and immunological association between bullous pemphigoid (BP) and several neurological or psychiatric diseases. Here, our aim was for the first time to specify whether an association exists between BP and frontotemporal lobar degeneration (FTLD). Medical histories of FTLD patients (N = 196) were screened for clinical comorbidity, and BP180 and BP230 autoantibodies were analyzed in the sera of FTLD patients (N = 70, including 24 C9orf72 repeat expansion carriers) by BP180-NC16A-ELISA and BP230-ELISA. One FTLD patient (C9orf72 repeat expansion carrier) had a comorbid diagnosis of BP. Increased levels of serum BP180 autoantibodies (cutoff value >9 U/ml) were detected more often in FTLD patients (10.0%) than in controls (4.9%). Moreover, elevated levels of both BP180 and BP230 autoantibodies were found more often in C9orf72 repeat expansion-carrying FTLD than non-carrying patients or controls. However, none of these differences reached a statistical significance likely due to our limited cohort size. In conclusion, our findings suggest that subset of FTLD patients especially with the C9orf72 repeat expansion may have an immunological association with BP.
Topics: Aged; Autoantibodies; Autoantigens; C9orf72 Protein; DNA Repeat Expansion; Dystonin; Female; Finland; Frontotemporal Lobar Degeneration; Humans; Male; Middle Aged; Non-Fibrillar Collagens; Pemphigoid, Bullous; Collagen Type XVII
PubMed: 30320585
DOI: 10.3233/JAD-180624 -
Acta Dermato-venereologica 2000Some patients with scabies develop bullae concomitantly with, or subsequently after, the occurrence of scabetic lesions. Although several immunofluorescence studies have... (Review)
Review
Some patients with scabies develop bullae concomitantly with, or subsequently after, the occurrence of scabetic lesions. Although several immunofluorescence studies have demonstrated immunoglobulin deposition in the basement membrane zone of bullous lesions, it remained unclear whether these antibodies are directed to bullous pemphigoid antigens. We clearly show that two scabetic patients with bullous eruptions had circulating antibodies against BP180 and/or BP230 as determined by Western blotting analysis. This is the first report to demonstrate that at least some of the bullous eruptions occurring in scabetics are true bullous pemphigoid.
Topics: Aged; Autoantibodies; Autoantigens; Blotting, Western; Carrier Proteins; Collagen; Cytoskeletal Proteins; Dystonin; Humans; Male; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Scabies; Collagen Type XVII
PubMed: 11028862
DOI: 10.1080/000155500750012171 -
The Journal of Investigative Dermatology Mar 2022
Topics: Autoantibodies; Autoantigens; Dystonin; Enzyme-Linked Immunosorbent Assay; Fractures, Bone; Humans; Non-Fibrillar Collagens
PubMed: 34883045
DOI: 10.1016/j.jid.2021.11.028 -
European Journal of Dermatology : EJD 2016The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180,...
BACKGROUND
The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen, both simultaneously and more rapidly than previous assays.
OBJECTIVES
The aim of this study was to evaluate the diagnostic accuracy of this kit for the diagnosis of pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita.
MATERIALS & METHODS
Dual-centre retrospective study in which 138 patients with autoimmune blistering diseases were compared to 40 controls
RESULTS
Using the MESACUP anti-Skin profile TEST, both sensitivities and specificities for desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen autoantibodies were similar to those obtained using previous, specific ELISA systems and 88% of the results were concordant without any significant difference.
CONCLUSION
The MESACUP anti-Skin profile TEST had a similar performance to previously produced ELISA systems. The novel kit can be used for rapid diagnosis of most common autoimmune blistering diseases and is especially suitable for identifying overlapping disorders.
Topics: Autoantibodies; Autoantigens; Collagen Type VII; Desmoglein 1; Desmoglein 3; Dystonin; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Non-Fibrillar Collagens; Retrospective Studies; Sensitivity and Specificity; Skin; Skin Diseases, Vesiculobullous; Collagen Type XVII
PubMed: 26771500
DOI: 10.1684/ejd.2015.2692 -
Der Hautarzt; Zeitschrift Fur... Jan 2000Pemphigoid gestationis (PG) is a rare pregnancy-associated autoimmune bullous disease characterized by autoantibodies to the 180 kD bullous pemphigoid antigen (BP180)....
BACKGROUND AND OBJECTIVE
Pemphigoid gestationis (PG) is a rare pregnancy-associated autoimmune bullous disease characterized by autoantibodies to the 180 kD bullous pemphigoid antigen (BP180). The clinical spectrum of PG is polymorphic and for diagnostic purposes, a skin biopsy is usually taken demonstrating the deposition of autoantibodies.
PATIENTS AND METHODS
From 2 patients, skin biopsies were obtained for histopathologic and immunofluorescence studies. Circulating autoantibodies were characterized by immunoblotting and ELISA using a recombinant form of the immunodominant BP180 NC16 A domain.
RESULTS
The 2 PG patients described here did not show blisters but complained about severe itching. In the first case, PG presented in the first trimester of the second pregnancy as an erythema-multiforme-like disease. The second patient developed urticarial plaques a few days after delivery. PG was diagnosed by the detection of autoantibodies against recombinant BP180 NC16 A by immunoblot and ELISA analysis and confirmed by linear deposits of C3 at the cutaneous basement membrane zone on direct immunofluorescence microscopy. Skin lesions healed with oral prednisolone.
CONCLUSIONS
In our two patients, non-bullous PG could be diagnosed by serological tests. Immunoblotting and ELISA might be sensitive and specific tools when screening sera of patients with pruritic skin lesions in pregnancy for the presence of autoantibodies to BP180. In some cases, these newer techniques may make a skin biopsy unnecessary.
Topics: Adult; Autoantibodies; Autoantigens; Biopsy; Carrier Proteins; Collagen; Complement C3; Cytoskeletal Proteins; Dystonin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Microscopy, Fluorescence; Nerve Tissue Proteins; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pregnancy; Pregnancy Complications; Skin; Collagen Type XVII
PubMed: 10663036
DOI: 10.1007/s001050050006 -
The Journal of Dermatology Oct 2016
Topics: Autoantibodies; Autoantigens; Basement Membrane; Biopsy; Dystonin; Female; Fluorescent Antibody Technique; Glucocorticoids; Humans; Middle Aged; Mouth Mucosa; Oral Ulcer; Pemphigoid, Benign Mucous Membrane; Prednisolone
PubMed: 27709732
DOI: 10.1111/1346-8138.13361 -
BMC Pediatrics Jun 2021MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. Previously, we had revealed the prognosis of MYCN target genes. However, the...
BACKGROUND
MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. Previously, we had revealed the prognosis of MYCN target genes. However, the prognostic effects of age related genes in neuroblastoma are unclear.
METHODS
The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. Genes differentially expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of age related genes ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B in pediatric neuroblastoma patients were determined by Kaplan-Meier survival.
RESULTS
In a pediatric pan-cancer analysis, age was associated with the overall survival of pediatric B-lineage acute lymphoblastic leukemia, neuroblastoma and wilms tumor in TARGET dataset. Moreover, the prognostic effects of age in neuroblastoma were validated using two independent neuroblastoma cohorts. Furthermore, age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B were highly expressed in MYCN non-amplified younger neuroblastoma patients. And the higher expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIF1B were associated with better prognosis of MYCN non-amplified neuroblastoma patients. DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified neuroblastoma younger patients with higher DST expression levels had the best clinical overall survival.
CONCLUSIONS
Age related gene DST was an independent prognostic factor in MYCN non-amplified neuroblastoma. MYCN non-amplified younger neuroblastoma patients with higher DST expression levels had the best clinical overall survival.
Topics: Child; Dystonin; Gene Amplification; Gene Expression; Humans; N-Myc Proto-Oncogene Protein; Neuroblastoma; Prognosis
PubMed: 34116676
DOI: 10.1186/s12887-021-02753-6 -
The American Journal of Gastroenterology Oct 2019
Topics: Autoantibodies; Autoantigens; Biomarkers; Biopsy; Deglutition Disorders; Delayed Diagnosis; Dystonin; Endoscopy, Digestive System; Esophagus; Female; Humans; Middle Aged; Non-Fibrillar Collagens; Pemphigoid, Benign Mucous Membrane; Referral and Consultation; Collagen Type XVII
PubMed: 31498153
DOI: 10.14309/ajg.0000000000000393 -
The British Journal of Dermatology Jan 2020
Topics: Autoantibodies; Autoantigens; Dystonin; Enzyme-Linked Immunosorbent Assay; Humans; Non-Fibrillar Collagens; Pemphigoid, Bullous
PubMed: 31301230
DOI: 10.1111/bjd.18343