Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases

Mühlen, Carlos Alberto von; Chan, Edward K. L.; Peebles, Carol; Imai, Haruhiko; Kiyosawa, Kendo; Tan, Eng M.

doi:10.1111/j.1365-2249.1995.tb03605.x

Cited by 24 publications

(5 citation statements)

References 65 publications

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“…Target autoantigens include actin exhibiting striated actin “cables” spanning the long axis of the cells. A similar staining was reported for antibody to the heavy chain of non-muscle myosin ( 32 ). The fibrillar filamentous pattern describes filaments and fibrils spreading out from the nuclear rim, often concentrated around the nucleus and extending into the cytoplasm (Figure 2 E).…”

Section: Cytoplasmic Patternssupporting

confidence: 81%

Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

et al. 2015

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During the 12th International Workshop on Autoantibodies and Autoimmunity held in Sao Paulo, Brazil, on August 28, 2014, a full day session was devoted to establishing a consensus on the nomenclature of staining patterns observed in the antinuclear antibody (ANA) indirect immunofluorescence test on HEp-2 cells. The current report summarizes the collective agreements with input from the host Brazilian and international communities that represented research, clinical, and diagnostic service laboratories. Patterns are categorized in three major groups (nuclear, cytoplasmic, and mitotic patterns) and each pattern has been defined and described in detail. The consensus nomenclature and representative patterns are made available online at the international consensus on antinuclear antibody pattern (ICAP) website (). To facilitate continuous improvement and input, specific comments on ICAP are encouraged and these will be discussed in subsequent ICAP meetings. The ultimate goal with the establishment of the ICAP is to promote harmonization and understanding of autoantibody test nomenclature, as well as interpretation guidelines for ANA testing, thereby optimizing usage in patient care.

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Section: Cytoplasmic Patternssupporting

confidence: 81%

Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

et al. 2015

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“… 2 ACTB Actin, cytoplasmic 1 (Beta-actin) (Nucleus) + 5.29 [ 79 ] 2 ACTBL2 Beta-actin-like protein 2 (Kappa-actin) + 5.39 ? 17 SPTAN1 Spectrin alpha chain non-erythrocytic 1, fodrin alpha chain + 5.22 [ 80 ] 7 MYH9 Myosin-9 + 5.50 [ 81 ] 4 TPM4 Tropomyosin alpha-4 chain + 4.67 [ 82 ] 3 TPM1 Tropomyosin alpha-1 chain + 4.69 [ 83 ] 2 TPM3 Tropomyosin alpha-3 chain + 4.68 [ 84 ] 2 TPM2 Tropomyosin beta chain + 4.66 ? …”

Section: Resultsmentioning

confidence: 99%

A proteomic repertoire of autoantigens identified from the classic autoantibody clinical test substrate HEp-2 cells

Wang¹,

Zhang

Rho³

et al. 2020

Clin Proteom

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Background Autoantibodies are a hallmark of autoimmune diseases. Autoantibody screening by indirect immunofluorescence staining of HEp-2 cells with patient sera is a current standard in clinical practice. Differential diagnosis of autoimmune disorders is based on commonly recognizable nuclear and cytoplasmic staining patterns. In this study, we attempted to identify as many autoantigens as possible from HEp-2 cells using a unique proteomic DS-affinity enrichment strategy. Methods HEp-2 cells were cultured and lysed. Total proteins were extracted from cell lysate and fractionated with DS-Sepharose resins. Proteins were eluted with salt gradients, and fractions with low to high affinity were collected and sequenced by mass spectrometry. Literature text mining was conducted to verify the autoantigenicity of each protein. Protein interaction network and pathway analyses were performed on all identified proteins. Results This study identified 107 proteins from fractions with low to high DS-affinity. Of these, 78 are verified autoantigens with previous reports as targets of autoantibodies, whereas 29 might be potential autoantigens yet to be verified. Among the 107 proteins, 82 can be located to nucleus and 15 to the mitotic cell cycle, which may correspond to the dominance of nuclear and mitotic staining patterns in HEp-2 test. There are 55 vesicle-associated proteins and 12 ribonucleoprotein granule proteins, which may contribute to the diverse speckled patterns in HEp-2 stains. There are also 32 proteins related to the cytoskeleton. Protein network analysis indicates that these proteins have significantly more interactions among themselves than would be expected of a random set, with the top 3 networks being mRNA metabolic process regulation, apoptosis, and DNA conformation change. Conclusions This study provides a proteomic repertoire of confirmed and potential autoantigens for future studies, and the findings are consistent with a mechanism for autoantigenicity: how self-molecules may form molecular complexes with DS to elicit autoimmunity. Our data contribute to the molecular etiology of autoimmunity and may deepen our understanding of autoimmune diseases.

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“…NuMA is another large coiled-coil protein located at the mitotic spindle pole and is the most common target autoantigen in serum samples with mitotic spindle apparatus staining. (39) Nonmuscle myosin (∼200 kDa) is a cytoskeletal autoantigen (40) qualified in the same group of high-molecular-weight and coiled-coil-rich autoantigens. Hence, it is intriguing that KIF20B is also characterized by extensive coiled-coil regions (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Monoclonal Antibody to M-Phase Phosphoprotein 1/Kinesin-Like Protein KIF20B

Fritzler

Brown

Zhang

2019

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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Kinesin-like protein KIF20B, originally named M-phase phosphoprotein 1 (MPP1), is a plus-end-directed kinesin-related protein that exhibits in vitro microtubule-binding and -bundling properties as well as microtubule-stimulated ATPase activity. It has been characterized as a slow molecular motor that moves toward the plus-end of microtubules. Human autoantibodies directed against KIF20B have been described in up to 25% of patients with idiopathic ataxia and less commonly in other neuropathies and autoinflammatory conditions. One of the limitations of research into the structure and function of KIF20B has been a reliable monoclonal antibody that can be used in a variety of applications. To establish a reference standard for anti-KIF20B immunoassays and facilitate studies on the role of KIF20B in developmental cell biology, we developed an IgG1 monoclonal antibody, 10C7, which reacts with the cognate KIF20B protein in Western immunoblots and in addressable laser bead immunoassays. In HEp2 cells, leptomeningeal pericytes, and transfected HEK293T cells, indirect immunofluorescence studies showed that reactivity was mainly localized to a proportion of interphase nuclei, but during metaphase, it was redistributed throughout the cytoplasm and perichromatin mass. Later in telophase/anaphase, KIF20B was localized to the stem body and midzone of the midbody. 10C7 also showed remarkable staining of a subset of cells in the cerebellum, ovary, and testis tissues. KIF20B was shown to have extensive coiled-coil domains. The monoclonal antibody, 10C7, will be of value to diagnostic laboratory scientists interested in having a reliable reference standard for anti-KIF20B immunoassays as well as cell, molecular, and developmental biology researchers.

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Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases

Cited by 24 publications

References 65 publications

Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014–2015

A proteomic repertoire of autoantigens identified from the classic autoantibody clinical test substrate HEp-2 cells

A Monoclonal Antibody to M-Phase Phosphoprotein 1/Kinesin-Like Protein KIF20B

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