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Article ; Online: Criteria for the pathogenicity of anticentromere (anti-CENP-B) autoantibodies in systemic sclerosis: comment on the article by van Leeuwen et al.

Senécal, Jean-Luc / Koenig, Martial / Archambault, Gabriel / Hoa, Sabrina

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 9, Page(s) 1606–1607

MeSH term(s)	Autoantibodies ; Autoantigens ; Centromere Protein B ; Humans ; Scleroderma, Systemic ; Virulence
Chemical Substances	Autoantibodies ; Autoantigens ; Centromere Protein B
Language	English
Publishing date	2022-08-09
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42159
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Article ; Online: Editorial: A New Classification of Adult Autoimmune Myositis.

Senécal, Jean-Luc / Raynauld, Jean-Pierre / Troyanov, Yves

Arthritis & rheumatology (Hoboken, N.J.)

2017 Volume 69, Issue 5, Page(s) 878–884

MeSH term(s)	Adult ; Autoimmune Diseases ; Child ; Dermatomyositis ; Humans ; Myositis ; Polymyositis ; Rheumatic Diseases ; Rheumatology ; United States
Language	English
Publishing date	2017-04-06
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.40063
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Article: Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis.

Koenig, Martial / Senécal, Jean-Luc / Mahler, Michael

The Journal of rheumatology

2017 Volume 44, Issue 12, Page(s) 1938–1939

MeSH term(s)	Autoantibodies/immunology ; Centromere/immunology ; Female ; Humans ; Middle Aged ; Scleroderma, Systemic/immunology ; Seroconversion
Chemical Substances	Autoantibodies
Language	English
Publishing date	2017-11-10
Publishing country	Canada
Document type	Case Reports ; Letter
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.170575
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Article ; Online: Pathogenic roles of autoantibodies in systemic sclerosis: Current understandings in pathogenesis.

Senécal, Jean-Luc / Hoa, Sabrina / Yang, Roger / Koenig, Martial

Journal of scleroderma and related disorders

2019 Volume 5, Issue 2, Page(s) 103–129

Abstract: The potential pathogenic role for autoantibodies in systemic sclerosis has captivated researchers for the past 40 years. This review answers the question whether there is yet sufficient knowledge to conclude that certain serum autoantibodies associated ... ...

Abstract	The potential pathogenic role for autoantibodies in systemic sclerosis has captivated researchers for the past 40 years. This review answers the question whether there is yet sufficient knowledge to conclude that certain serum autoantibodies associated with systemic sclerosis contribute to its pathogenesis. Definitions for pathogenic, pathogenetic and functional autoantibodies are formulated, and the need to differentiate these autoantibodies from natural autoantibodies is emphasized. In addition, seven criteria for the identification of pathogenic autoantibodies are proposed. Experimental evidence is reviewed relevant to the classic systemic sclerosis antinuclear autoantibodies, anti-topoisomerase I and anticentromere, and to functional autoantibodies to endothelin 1 type A receptor, angiotensin II type 1 receptor, muscarinic receptor 3, platelet-derived growth factor receptor, chemokine receptors CXCR3 and CXCR4, estrogen receptor α, and CD22. Pathogenic evidence is also reviewed for anti-matrix metalloproteinases 1 and 3, anti-fibrillin 1, anti-IFI16, anti-eIF2B, anti-ICAM-1, and anti-RuvBL1/RuvBL2 autoantibodies. For each autoantibody, objective evidence for a pathogenic role is scored qualitatively according to the seven pathogenicity criteria. It is concluded that anti-topoisomerase I is the single autoantibody specificity with the most evidence in favor of a pathogenic role in systemic sclerosis, followed by anticentromere. However, these autoantibodies have not been demonstrated yet to fulfill completely the seven proposed criteria for pathogenicity. Their contributory roles to the pathogenesis of systemic sclerosis remain possible but not yet conclusively demonstrated. With respect to functional autoantibodies and other autoantibodies, only a few criteria for pathogenicity are fulfilled. Their common presence in healthy and disease controls suggests that major subsets of these immunoglobulins are natural autoantibodies. While some of these autoantibodies may be
Language	English
Publishing date	2019-09-09
Publishing country	England
Document type	Journal Article ; Review
ISSN	2397-1991
ISSN (online)	2397-1991
DOI	10.1177/2397198319870667
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Article ; Online: Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis.

Giannini, Margherita / Ellezam, Benjamin / Leclair, Valérie / Lefebvre, Frédéric / Troyanov, Yves / Hudson, Marie / Senécal, Jean-Luc / Geny, Bernard / Landon-Cardinal, Océane / Meyer, Alain

Frontiers in immunology

2023 Volume 13, Page(s) 974078

Abstract: Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two ... ...

Abstract	Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated "scleromyositis", should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. "seronegative" scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients.
MeSH term(s)	Humans ; Quality of Life ; Myositis/diagnosis ; Myositis/etiology ; Myositis/therapy ; Autoimmune Diseases/complications ; Scleroderma, Systemic/diagnosis ; Scleroderma, Systemic/therapy ; Scleroderma, Systemic/complications ; Myositis, Inclusion Body
Language	English
Publishing date	2023-01-26
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.974078
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Article ; Online: Anti-SMN autoantibodies in mixed connective tissue disease are associated with a severe systemic sclerosis phenotype.

El Kamouni, Hajar / S Jalaledin, Darya / Albert, Alexandra / Hoa, Sabrina / Vo, Caroline / Bourré-Tessier, Josiane / Rich, Éric / Goulet, Jean-Richard / Koenig, Martial / Pérez, Gemma / Choi, May Y / Troyanov, Yves / Satoh, Minoru / Fritzler, Marvin J / Senécal, Jean-Luc / Landon-Cardinal, Océane

RMD open

2023 Volume 9, Issue 4

Abstract: Objectives: The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis ... ...

Abstract	Objectives: The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs. Methods: A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with <300 mean fluorescence intensity (MFI) as normal reference range, 300-999 MFI as low-titre and ≥1000 MFI as high-titre positivity. Comparison of clinical features between anti-SMN+ and anti-SMN- subgroups used two-tailed Fisher's exact test, and logistic regression analyses. Results: Sixty-six patients were included. Median age at MCTD diagnosis was 40.6 years, and duration of follow-up was 12 years. Based on the highest available titre, 39 (59%) were anti-SMN+: 10 (26%) had low titre and 29 (74%) had high titre. Anti-SMN+ patients had a higher frequency of fingertip pitting scars (anti-SMN+ 23% vs anti-SMN- 4%, p=0.04), lower gastrointestinal (GI) involvement (26% vs 4%, p=0.04), and myocarditis (16% vs 0%, p=0.04). The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among high-titre anti-SMN+ patients: adjusted OR 7.79 (2.33 to 30.45, p=0.002). Conclusions: Anti-SMN aAbs were present in 59% of our MCTD cohort. Their presence, especially at high-titres, was associated with a severe systemic sclerosis (scleroderma) phenotype including myositis, myocarditis and lower GI involvement.
MeSH term(s)	Humans ; Autoantibodies ; Mixed Connective Tissue Disease/complications ; Mixed Connective Tissue Disease/diagnosis ; Retrospective Studies ; Cicatrix/complications ; Myocarditis/complications ; Scleroderma, Systemic/complications ; Scleroderma, Systemic/diagnosis ; Myositis/complications ; Phenotype
Chemical Substances	Autoantibodies
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003431
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Article ; Online: Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype.

Koenig, Martial / Bentow, Chelsea / Satoh, Minoru / Fritzler, Marvin J / Senécal, Jean-Luc / Mahler, Michael

Rheumatology (Oxford, England)

2019 Volume 58, Issue 10, Page(s) 1784–1793

Abstract: Objective: Detection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. ...

Abstract	Objective: Detection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. However, very little is known about the epitope distribution of this autoantigen. Consequently, we screened Rpp25, Rpp38 and hPop1 for B cell epitopes and evaluated their clinical relevance. Methods: Serum pools with (n = 2) and without (n = 1) anti-Th/To autoantibodies were generated and used for epitope discovery. Identified biomarker candidate sequences were then utilized to synthesize synthetic, biotinylated, soluble peptides. The peptides were tested to determine reactivity with sera from SSc cohorts (n = 202) and controls (n = 159) using a chemiluminescence immunoassay. Additionally, samples were also tested for antibodies to full-length recombinant Rpp25 antibodies by chemiluminescence immunoassay. Results: Several immunodominant regions were found on the three proteins. The strongest reactivity was observed with an Rpp38 peptide (aa 229-243). Autoantibodies to the Rpp38 peptide were detected in 8/149 (5.4%) limited cutaneous SSc patients, but not in any of 159 controls (P = 0.003 by two-sided Fisher's exact probability test). Although reactivity to the novel antigenic peptide was correlated with the binding to Rpp25 (rho = 0.44; P < 0.0001), subsets of patient sera either reacted strongly with Rpp25 or with the novel Rpp38-derived peptide. Conclusion: A novel Rpp38 epitope holds promise to increase the sensitivity in the detection of anti-Th/To autoantibodies, thus enhancing the serological diagnosis of SSc.
MeSH term(s)	Autoantibodies/blood ; Autoantibodies/immunology ; Autoantigens/blood ; Autoantigens/immunology ; Epitopes, B-Lymphocyte/immunology ; Humans ; Immunodominant Epitopes ; Phenotype ; Ribonuclease P/immunology ; Scleroderma, Systemic/immunology
Chemical Substances	Autoantibodies ; Autoantigens ; Epitopes, B-Lymphocyte ; Immunodominant Epitopes ; RPP38 protein, human (EC 3.1.26.5) ; Ribonuclease P (EC 3.1.26.5)
Language	English
Publishing date	2019-07-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kez123
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Article ; Online: Anti-SMN autoantibodies in mixed connective tissue disease are associated with a severe systemic sclerosis phenotype

Minoru Satoh / Océane Landon-Cardinal / Alexandra Albert / Sabrina Hoa / Jean-Luc Senecal / Martial Koenig / Josiane Bourré-Tessier / Eric Rich / Jean-Richard Goulet / Yves Troyanov / Hajar El Kamouni / Darya S. Jalaledin / Caroline Vo / Gemma Pérez / May Y. Choi / Marvin J. Fritzler

RMD Open, Vol 9, Iss

2023 Volume 4

Abstract: Objectives The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis ... ...

Abstract	Objectives The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs.Methods A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with <300 mean fluorescence intensity (MFI) as normal reference range, 300–999 MFI as low-titre and ≥1000 MFI as high-titre positivity. Comparison of clinical features between anti-SMN+ and anti-SMN− subgroups used two-tailed Fisher’s exact test, and logistic regression analyses.Results Sixty-six patients were included. Median age at MCTD diagnosis was 40.6 years, and duration of follow-up was 12 years. Based on the highest available titre, 39 (59%) were anti-SMN+: 10 (26%) had low titre and 29 (74%) had high titre. Anti-SMN+ patients had a higher frequency of fingertip pitting scars (anti-SMN+ 23% vs anti-SMN− 4%, p=0.04), lower gastrointestinal (GI) involvement (26% vs 4%, p=0.04), and myocarditis (16% vs 0%, p=0.04). The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among high-titre anti-SMN+ patients: adjusted OR 7.79 (2.33 to 30.45, p=0.002).Conclusions Anti-SMN aAbs were present in 59% of our MCTD cohort. Their presence, especially at high-titres, was associated with a severe systemic sclerosis (scleroderma) phenotype including myositis, myocarditis and lower GI involvement.
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
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Article ; Online: Capillary pathology with prominent basement membrane reduplication is the hallmark histopathological feature of scleromyositis.

Ellezam, Benjamin / Leclair, Valérie / Troyanov, Yves / Bersali, Imane / Giannini, Margherita / Hoa, Sabrina / Bourré-Tessier, Josiane / Nadon, Valérie / Drouin, Julie / Karamchandani, Jason / O'Ferrall, Erin / Lannes, Béatrice / Satoh, Minoru / Fritzler, Marvin J / Senécal, Jean-Luc / Hudson, Marie / Meyer, Alain / Landon-Cardinal, Océane

Neuropathology and applied neurobiology

2022 Volume 48, Issue 7, Page(s) e12840

Abstract: Aims: We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates ' ... ...

Abstract	Aims: We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets. Methods: Muscle biopsies from a total of 60 SM patients and 43 AIM controls from two independent cohorts were examined by electron microscopy, collagen-4 immunofluorescence (Col4IF) and routine light microscopy. Results: Ultrastructural examination revealed prominent capillary basement membrane (BM) reduplication (4+ layers in >50% of capillaries) in 65% of SM vs 0% of AIM controls (p < 0.001). In SM cases without prominent BM reduplication, capillary dilation was the most distinctive feature, present in 8% of capillaries in SM vs 2% in controls (p = 0.001). Accumulation of ensheathed pericyte processes was another characteristic feature of SM and closely correlated with the degree of BM reduplication (r = 0.833, p < 0.001). On light microscopy, BM marker Col4IF revealed more frequent capillary enlargement in SM than in controls (84% vs 21%, p < 0.001). SM cases were classified as non-inflammatory myopathy (36%), non-specific myositis (33%) or immune-mediated necrotizing myopathy (31%), but despite this histopathological heterogeneity, prominent BM reduplication remained a constant finding. In the 16 SM patients with early/mild SSc features, 63% showed prominent BM reduplication. Conclusions: These results show that capillary pathology, and in particular prominent capillary BM reduplication, is the hallmark histopathological feature of SM even in patients with early/mild SSc and support the concept of SM as an organ manifestation of SSc and a distinct subset of AIM.
MeSH term(s)	Humans ; Capillaries/pathology ; Capillaries/ultrastructure ; Basement Membrane/pathology ; Basement Membrane/ultrastructure ; Myositis/pathology ; Microscopy, Electron ; Muscular Diseases/pathology
Language	English
Publishing date	2022-08-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80371-6
ISSN	1365-2990 ; 0305-1846
ISSN (online)	1365-2990
ISSN	0305-1846
DOI	10.1111/nan.12840
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Article ; Online: Histopathological features of systemic sclerosis-associated myopathy: A scoping review.

Lefebvre, Frédéric / Giannini, Margherita / Ellezam, Benjamin / Leclair, Valérie / Troyanov, Yves / Hoa, Sabrina / Bourré-Tessier, Josiane / Satoh, Minoru / Fritzler, Marvin J / Senécal, Jean-Luc / Hudson, Marie / Meyer, Alain / Landon-Cardinal, Océane

Autoimmunity reviews

2021 Volume 20, Issue 7, Page(s) 102851

Abstract: Background: Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to ... ...

Abstract	Background: Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM. Methods: A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases: PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol. Results: Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n = 227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n = 8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n = 104/218) of biopsies, and was predominantly perifascicular in 19% (n = 6/31), with necrosis reported in 56% (n = 162/290) of cases. Sarcolemmal MHC-I upregulation was found in 72% (n = 64/89) of biopsies. Non-specified C5b-9 deposition was described in 39% of muscle biopsies (n = 28/72). Neurogenic features were present in 23% (n = 44/191); endomysial fibrosis was reported in 35% (n = 120/340); and rimmed vacuoles were observed in 32% (n = 11/34) of biopsies. Capillaropathy, such as capillary dropout and/or ultrastructural endothelial abnormalities, was reported in 33% (n = 43/129) of cases. Reported ENMC categories were mainly polymyositis (21%), non-specific myositis (19%), immune-mediated necrotizing myopathy (16%), and dermatomyositis (8%). Histopathological features were analyzed according to serological subtypes in 28 studies, including anti-PM-Scl (n = 48), -Ku (n = 23) and -U1RNP (n = 90). Most of these biopsies demonstrated inflammatory infiltrates (range 49-85%) as well as MHC-I expression (range 63-81%). Necrosis was associated with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively. Conclusion: Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.
MeSH term(s)	Autoantibodies ; Humans ; Muscular Diseases ; Myositis/complications ; Polymyositis ; Scleroderma, Systemic/complications
Chemical Substances	Autoantibodies
Language	English
Publishing date	2021-05-07
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2021.102851
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