Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations
Abstract Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is uncl...
Gespeichert in:
Veröffentlicht in: | Journal of neuropathology and experimental neurology 2020-04, Vol.79 (4), p.448-457 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 457 |
---|---|
container_issue | 4 |
container_start_page | 448 |
container_title | Journal of neuropathology and experimental neurology |
container_volume | 79 |
creator | Kurashige, Takashi Murao, Tomomi Mine, Naoko Sugiura, Tomohito Inazuka, Yukiko Kuraoka, Kazuya Takahashi, Tetsuya Maruyama, Hirofumi Torii, Tsuyoshi |
description | Abstract
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p |
doi_str_mv | 10.1093/jnen/nlaa006 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7092361</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A644230327</galeid><oup_id>10.1093/jnen/nlaa006</oup_id><sourcerecordid>A644230327</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6186-969b3087b8ad83d2ef8128c4bd8bd908b6dcb78eb1221bfee62f56a9004fb3d43</originalsourceid><addsrcrecordid>eNp9kktv1DAUhSMEokNhxxpFYgEL0l4_4jibSsMI2kpTgXisLdtxGg-OHeKko_x7MszQUgTICz_ud87VtU6SPEdwgqAkpxtv_Kl3UgKwB8kC5TnNWF7wh8kCAOOMACuPkicxbgCghJI-To4IRvMF0UViln6w2cXV-epTujuqUE3ZxxDtYG9MejWFTg7NlH5uwjamb7XL8F310tdOtq0cbPCp9FW6ntquCXoarE6XWo_t6H4W49PkUS1dNM8O-3Hy9f27L6uLbP3h_HK1XGeaIc6ykpWKAC8UlxUnFTY1R5hrqiquqhK4YpVWBTcKYYxUbQzDdc5kCUBrRSpKjpOzvW83qtZU2vihl050vW1lP4kgrbhf8bYR1-FGFFBiwtBs8Ppg0Ifvo4mDaG3UxjnpTRijmKEcA8lRMaMv_0A3Yez9PJ7AFDNacg70jrqWzgjr6zD31TtTsWSUYgIE77xO_kLNqzKt1cGb2s7v9wRv9gLdhxh7U9_OiEDsYiF2sRCHWMz4i9__5Rb-lYMZgD2wDW4wffzmxq3pRWOkG5p_eb7aS8LY_b_7DzR90rM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2426498804</pqid></control><display><type>article</type><title>Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Kurashige, Takashi ; Murao, Tomomi ; Mine, Naoko ; Sugiura, Tomohito ; Inazuka, Yukiko ; Kuraoka, Kazuya ; Takahashi, Tetsuya ; Maruyama, Hirofumi ; Torii, Tsuyoshi</creator><creatorcontrib>Kurashige, Takashi ; Murao, Tomomi ; Mine, Naoko ; Sugiura, Tomohito ; Inazuka, Yukiko ; Kuraoka, Kazuya ; Takahashi, Tetsuya ; Maruyama, Hirofumi ; Torii, Tsuyoshi</creatorcontrib><description>Abstract
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlaa006</identifier><identifier>PMID: 32100014</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antibodies ; Autoantibodies ; Diagnosis ; Genetic aspects ; Health aspects ; Lymphocytes ; Myositis ; Original ; Oxidoreductases ; Statins</subject><ispartof>Journal of neuropathology and experimental neurology, 2020-04, Vol.79 (4), p.448-457</ispartof><rights>2020 American Association of Neuropathologists, Inc. 2020</rights><rights>2020 by American Association of Neuropathologists, Inc.</rights><rights>2020 American Association of Neuropathologists, Inc.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6186-969b3087b8ad83d2ef8128c4bd8bd908b6dcb78eb1221bfee62f56a9004fb3d43</citedby><cites>FETCH-LOGICAL-c6186-969b3087b8ad83d2ef8128c4bd8bd908b6dcb78eb1221bfee62f56a9004fb3d43</cites><orcidid>0000-0002-5206-5979</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32100014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kurashige, Takashi</creatorcontrib><creatorcontrib>Murao, Tomomi</creatorcontrib><creatorcontrib>Mine, Naoko</creatorcontrib><creatorcontrib>Sugiura, Tomohito</creatorcontrib><creatorcontrib>Inazuka, Yukiko</creatorcontrib><creatorcontrib>Kuraoka, Kazuya</creatorcontrib><creatorcontrib>Takahashi, Tetsuya</creatorcontrib><creatorcontrib>Maruyama, Hirofumi</creatorcontrib><creatorcontrib>Torii, Tsuyoshi</creatorcontrib><title>Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Abstract
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.</description><subject>Antibodies</subject><subject>Autoantibodies</subject><subject>Diagnosis</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Lymphocytes</subject><subject>Myositis</subject><subject>Original</subject><subject>Oxidoreductases</subject><subject>Statins</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kktv1DAUhSMEokNhxxpFYgEL0l4_4jibSsMI2kpTgXisLdtxGg-OHeKko_x7MszQUgTICz_ud87VtU6SPEdwgqAkpxtv_Kl3UgKwB8kC5TnNWF7wh8kCAOOMACuPkicxbgCghJI-To4IRvMF0UViln6w2cXV-epTujuqUE3ZxxDtYG9MejWFTg7NlH5uwjamb7XL8F310tdOtq0cbPCp9FW6ntquCXoarE6XWo_t6H4W49PkUS1dNM8O-3Hy9f27L6uLbP3h_HK1XGeaIc6ykpWKAC8UlxUnFTY1R5hrqiquqhK4YpVWBTcKYYxUbQzDdc5kCUBrRSpKjpOzvW83qtZU2vihl050vW1lP4kgrbhf8bYR1-FGFFBiwtBs8Ppg0Ifvo4mDaG3UxjnpTRijmKEcA8lRMaMv_0A3Yez9PJ7AFDNacg70jrqWzgjr6zD31TtTsWSUYgIE77xO_kLNqzKt1cGb2s7v9wRv9gLdhxh7U9_OiEDsYiF2sRCHWMz4i9__5Rb-lYMZgD2wDW4wffzmxq3pRWOkG5p_eb7aS8LY_b_7DzR90rM</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Kurashige, Takashi</creator><creator>Murao, Tomomi</creator><creator>Mine, Naoko</creator><creator>Sugiura, Tomohito</creator><creator>Inazuka, Yukiko</creator><creator>Kuraoka, Kazuya</creator><creator>Takahashi, Tetsuya</creator><creator>Maruyama, Hirofumi</creator><creator>Torii, Tsuyoshi</creator><general>Oxford University Press</general><general>by American Association of Neuropathologists, Inc</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5206-5979</orcidid></search><sort><creationdate>20200401</creationdate><title>Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations</title><author>Kurashige, Takashi ; Murao, Tomomi ; Mine, Naoko ; Sugiura, Tomohito ; Inazuka, Yukiko ; Kuraoka, Kazuya ; Takahashi, Tetsuya ; Maruyama, Hirofumi ; Torii, Tsuyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6186-969b3087b8ad83d2ef8128c4bd8bd908b6dcb78eb1221bfee62f56a9004fb3d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies</topic><topic>Autoantibodies</topic><topic>Diagnosis</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Lymphocytes</topic><topic>Myositis</topic><topic>Original</topic><topic>Oxidoreductases</topic><topic>Statins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurashige, Takashi</creatorcontrib><creatorcontrib>Murao, Tomomi</creatorcontrib><creatorcontrib>Mine, Naoko</creatorcontrib><creatorcontrib>Sugiura, Tomohito</creatorcontrib><creatorcontrib>Inazuka, Yukiko</creatorcontrib><creatorcontrib>Kuraoka, Kazuya</creatorcontrib><creatorcontrib>Takahashi, Tetsuya</creatorcontrib><creatorcontrib>Maruyama, Hirofumi</creatorcontrib><creatorcontrib>Torii, Tsuyoshi</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kurashige, Takashi</au><au>Murao, Tomomi</au><au>Mine, Naoko</au><au>Sugiura, Tomohito</au><au>Inazuka, Yukiko</au><au>Kuraoka, Kazuya</au><au>Takahashi, Tetsuya</au><au>Maruyama, Hirofumi</au><au>Torii, Tsuyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>79</volume><issue>4</issue><spage>448</spage><epage>457</epage><pages>448-457</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>Abstract
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32100014</pmid><doi>10.1093/jnen/nlaa006</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5206-5979</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-3069 |
ispartof | Journal of neuropathology and experimental neurology, 2020-04, Vol.79 (4), p.448-457 |
issn | 0022-3069 1554-6578 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7092361 |
source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
subjects | Antibodies Autoantibodies Diagnosis Genetic aspects Health aspects Lymphocytes Myositis Original Oxidoreductases Statins |
title | Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T07%3A03%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Anti-HMGCR%20Antibody-Positive%20Myopathy%20Shows%20Bcl-2-Positive%20Inflammation%20and%20Lymphocytic%20Accumulations&rft.jtitle=Journal%20of%20neuropathology%20and%20experimental%20neurology&rft.au=Kurashige,%20Takashi&rft.date=2020-04-01&rft.volume=79&rft.issue=4&rft.spage=448&rft.epage=457&rft.pages=448-457&rft.issn=0022-3069&rft.eissn=1554-6578&rft_id=info:doi/10.1093/jnen/nlaa006&rft_dat=%3Cgale_pubme%3EA644230327%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2426498804&rft_id=info:pmid/32100014&rft_galeid=A644230327&rft_oup_id=10.1093/jnen/nlaa006&rfr_iscdi=true |