A dermatomyositis and scleroderma overlap syndrome with a remarkable high titer of anti-exosome antibodies

Gutiérrez-Ramos, R; Lez-Díaz, V Gonz; Pacheco-Tovar, MariaGuadalupe; Luna, María Argelia López; Avalos‐Díaz, Esperanza; Herrera‐Esparza, Rafael

doi:10.4081/reumatismo.2008.296

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…Like many aab responses, aabs to the PM/Scl macromolecular complex likely undergo intermolecular epitope spreading. For example, Gutiérrez-Ramos and colleagues [ 6 ] recently reported a patient with high anti-PM/Scl aab titres identified by IIF and confirmed by IB (100 kDa band). Three months later, the patient's serum contained aabs to another 39 kDa protein that probably corresponded to an aberrant PM/Scl-75, suggesting an epitope spreading phenomenon [ 6 ].…”

Section: Major and Early Pm/scl Epitopementioning

confidence: 99%

“…For example, Gutiérrez-Ramos and colleagues [ 6 ] recently reported a patient with high anti-PM/Scl aab titres identified by IIF and confirmed by IB (100 kDa band). Three months later, the patient's serum contained aabs to another 39 kDa protein that probably corresponded to an aberrant PM/Scl-75, suggesting an epitope spreading phenomenon [ 6 ]. Similarly, immunization of rabbits with the PM1-Alpha peptide was attended by intermolecular epitope spreading to other exosome components [ 2 ].…”

Section: Major and Early Pm/scl Epitopementioning

confidence: 99%

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The changing landscape of the clinical value of the PM/Scl autoantibody system

Mähler

Fritzler

2009

Arthritis Res Ther

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Autoantibodies to the polymyositis/scleroderma (PM/Scl) complex have been associated with systemic sclerosis and PM/Scl overlap syndrome. The report of Hanke and colleagues in a recent issue of Arthritis Research and Therapy is the first to describe the separate evaluation of anti-PM/Scl-75c and PM/Scl-100 autoantibodies and their relationship to clinical manifestations of systemic sclerosis. Several observations are of paramount interest, but are not in general agreement with earlier studies. These include the prevalence of anti-PM/Scl antibodies in systemic sclerosis, the association with certain clinical manifestations and prognosis of patients. This report will hopefully trigger systematic multi-centre studies to confirm and/or elucidate the novel line immunoassay and clinical associations. BackgroundA characteristic feature of patients with systemic sclerosis (SSc; or scleroderma (Scl)) are anti-nucleolar antibodies (ANoAs), including autoantibodies (aabs) to components of the exosome, known also as the polymyositis/scleroderma (PM/Scl) complex [1,2]. While the majority of the anti-PM/Scl reactivity is directed against PM/Scl-75c and PM/Scl-100, many of the other nine core exosome components are also targeted, albeit with lower frequency and apparently limited diagnostic value [2]. Detection of PM/Scl antibodiesHistorically, anti-PM/Scl aabs were associated with PM/Scl overlap syndrome and were detected by indirect immunofluorescence (IIF) on HEp-2 cells, immunodiffusion, immunoblotting (IB), and/or immunoprecipitation. The clinical usefulness of PM/Scl aabs detected by IB and IIF was limited due to weak reactivity on IB and interference of other ANoAs in IIF. More recently, recombinant proteins (primarily PM/Scl-100) have been used as antigen targets in immunoassays, and a peptide-based PM1-Alpha enzyme-linked immunosorbent assay (ELISA) was reported to demonstrate higher sensitivity than traditional methods for the detection of anti-PM/Scl aabs [2][3][4]. Line immunoassays (LIAs), the precursor of today's more sophisticated multiplex assays such as addressable laser bead assays (ALBIAs), have become a popular technique for the simultaneous detection of aabs [5]. Several LIAs for the detection of PM/Scl aabs are available, covering a variety of myositis-and/or SSc-associated autoantigens; all of them using the PM/Scl-100 antigen to detect anti-PM/Scl reactivity [2]. With an increasing number of diagnostic platforms to test anti-PM/Scl reactivity, more diligent attention needs to be given to standardizing the autoantigens used in assays and the various platforms (LIA, ELISA, ALBIA) in which they are employed [5]. Major and early PM/Scl epitopeLike many aab responses, aabs to the PM/Scl macromolecular complex likely undergo intermolecular epitope spreading. For example, Gutiérrez-Ramos and colleagues [6] recently reported a patient with high anti-PM/Scl aab titres identified by IIF and confirmed by IB (100 kDa band). Three months later, the patient's serum contained aabs to another 39 kDa protein tha...

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Section: Major and Early Pm/scl Epitopementioning

confidence: 99%

Section: Major and Early Pm/scl Epitopementioning

confidence: 99%

The changing landscape of the clinical value of the PM/Scl autoantibody system

Mähler

Fritzler

2009

Arthritis Res Ther

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“…Previous studies have demonstrated that hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p and hCsl4p are six novel human exosome components . Autoantibodies directed to the human exosome components (hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p and hCsl4p) were detected in sera from scleroderma patients and the polymyositis/scleroderma overlap syndrome …”

Section: Importance Of Exosomes In Chronic Inflammatory Skin Diseasesmentioning

confidence: 99%

Exosomes in chronic inflammatory skin diseases and skin tumors

Wang

Jin

2019

Experimental Dermatology

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Exosomes are membrane vesicles of endocytic origin that can mediate communication between cells and the transport of cellular components such as microRNAs, mRNAs, proteins and DNA. Recently, exosomes have been under investigation for their significant roles in both healthy physiology and disease states. Herein, we review the role of exosomes in chronic inflammatory skin diseases and skin tumors, especially focusing on systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous pemphigoid and melanoma. Moreover, we emphasize the involvement of changes in exosome cargo in the regulation of these diseases.

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“…A previous study demonstrated that patients with scleroderma had a reduced level of exosomes in their serum, which was predominantly due to vascular abnormalities disrupting the transportation of exosomes derived from the fibrocytes of skin tissue (68,87). However, in dermatomyositis and scleroderma overlap syndrome, exosomes exist as an autoantigenic complex (88,89).…”

Section: Exosomes and Other Skin Diseasesmentioning

confidence: 99%

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

Liu

Wang

2018

biom rep

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Abstract. Exosomes are one of the most potent intercellular communicators, which are able to communicate with adjacent or distant cells. Exosomes deliver various bioactive molecules, including membrane receptors, proteins, mRNA and microRNA, to target cells and serve roles. Recent studies have demonstrated that exosomes may regulate the functions and diseases of the skin, which is the largest organ of the human body. The abnormal functions of the skin lead to the progression of scleroderma, melanoma, baldness and other diseases. A previous study has demonstrated that epithelial progenitor cells are rich in several subunits of exosomes that may maintain the proliferative capacity of these epithelial progenitor cells, which is essential for the development of the epidermis. Exosomes derived from human adipose mesenchymal stem cells accelerate skin wound healing by optimizing fibroblast properties; this is beneficial for the recovery of postoperative and other wounds. Exosomes derived from adipocytes promote melanoma migration and invasion through fatty acid oxidation; therefore, in the clinic, it may be possible to improve the prognosis of patients with melanoma by reducing their body fat content. Exosomes derived from keratinocytes modulate melanocyte pigmentation, which has been utilized as a novel mechanism for the regulation of pigmentation in conditions including Moynahan syndrome and albinism. Meanwhile, scleroderma patients with vascular abnormalities may experience decreased serum exosome levels; it may therefore be possible to detect the exosome content in sera in order to diagnose and treat scleroderma. In addition, the use of exosomes has been suggested to promote or enhance hair growth, which has been demonstrated to be highly effective. These studies have provided new opportunities and therapeutic strategies for understanding how exosomes regulate intercellular communication in pathological processes of the skin.

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A dermatomyositis and scleroderma overlap syndrome with a remarkable high titer of anti-exosome antibodies

Cited by 9 publications

References 10 publications

The changing landscape of the clinical value of the PM/Scl autoantibody system

The changing landscape of the clinical value of the PM/Scl autoantibody system

Exosomes in chronic inflammatory skin diseases and skin tumors

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

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