Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease
IgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with Ig...
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| Veröffentlicht in: | PloS one 2015-05, Vol.10 (5), p.e0126582-e0126582 |
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| creator | Nakajima, Akio Masaki, Yasufumi Nakamura, Takuji Kawanami, Takafumi Ishigaki, Yasuhito Takegami, Tsutomu Kawano, Mitsuhiro Yamada, Kazunori Tsukamoto, Norifumi Matsui, Shoko Saeki, Takako Okazaki, Kazuichi Kamisawa, Terumi Miyashita, Taiichiro Yakushijin, Yoshihiro Fujikawa, Keita Yamamoto, Motohisa Hamano, Hideaki Origuchi, Tomoki Hirata, Shintaro Tsuboi, Hiroto Sumida, Takayuki Morimoto, Hisanori Sato, Tomomi Iwao, Haruka Miki, Miyuki Sakai, Tomoyuki Fujita, Yoshimasa Tanaka, Masao Fukushima, Toshihiro Okazaki, Toshiro Umehara, Hisanori |
| description | IgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.
Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.
DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.
The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity. |
| doi_str_mv | 10.1371/journal.pone.0126582 |
| format | Article |
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Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.
DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.
The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0126582</identifier><identifier>PMID: 25973893</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Abnormalities ; Adult ; Aged ; Aged, 80 and over ; Allergies ; alpha-Defensins - genetics ; alpha-Defensins - metabolism ; Asthma ; Autoimmune Diseases - immunology ; Autoimmune Diseases - pathology ; Blood ; Care and treatment ; Case-Control Studies ; Cell cycle ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Charcot-Leyden crystal protein ; Control methods ; Cytokines ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA microarrays ; Down-Regulation ; Etiology ; Female ; Gastroenterology ; Gene expression ; Genes ; Genetic aspects ; Glycoproteins - genetics ; Glycoproteins - metabolism ; Hematology ; Hospitals ; Humans ; Hypersensitivity ; Immune system ; Immunity ; Immunity (Disease) ; Immunity, Innate - genetics ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunologic deficiency syndromes ; Immunology ; Infiltration ; Inflammation ; Innate immunity ; Interleukin 8 ; Interleukin 8 receptors ; Internal medicine ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - cytology ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Lymphocytes T ; Lysophospholipase - genetics ; Lysophospholipase - metabolism ; Male ; Medical research ; Medicine ; Membrane proteins ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Middle Aged ; Neutrophils ; Oligonucleotide Array Sequence Analysis ; Pancreatitis ; Pathogenesis ; Patients ; Peripheral blood mononuclear cells ; Plasma cells ; Polymerase chain reaction ; Proteins ; Real time ; Real-Time Polymerase Chain Reaction ; Receptors ; Receptors, Interleukin-8 - genetics ; Receptors, Interleukin-8 - metabolism ; Rheumatology ; Ribonucleic acid ; Risk factors ; RNA ; Steroids ; Th2 Cells - cytology ; Th2 Cells - immunology ; Therapy ; Up-Regulation</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0126582-e0126582</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Nakajima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Nakajima et al 2015 Nakajima et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-42bbcf321fe63081892f58c64f7e8c99354cc4a0612984f7cfba89ca46b100f43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431830/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431830/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25973893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Esteban, Francisco J.</contributor><creatorcontrib>Nakajima, Akio</creatorcontrib><creatorcontrib>Masaki, Yasufumi</creatorcontrib><creatorcontrib>Nakamura, Takuji</creatorcontrib><creatorcontrib>Kawanami, Takafumi</creatorcontrib><creatorcontrib>Ishigaki, Yasuhito</creatorcontrib><creatorcontrib>Takegami, Tsutomu</creatorcontrib><creatorcontrib>Kawano, Mitsuhiro</creatorcontrib><creatorcontrib>Yamada, Kazunori</creatorcontrib><creatorcontrib>Tsukamoto, Norifumi</creatorcontrib><creatorcontrib>Matsui, Shoko</creatorcontrib><creatorcontrib>Saeki, Takako</creatorcontrib><creatorcontrib>Okazaki, Kazuichi</creatorcontrib><creatorcontrib>Kamisawa, Terumi</creatorcontrib><creatorcontrib>Miyashita, Taiichiro</creatorcontrib><creatorcontrib>Yakushijin, Yoshihiro</creatorcontrib><creatorcontrib>Fujikawa, Keita</creatorcontrib><creatorcontrib>Yamamoto, Motohisa</creatorcontrib><creatorcontrib>Hamano, Hideaki</creatorcontrib><creatorcontrib>Origuchi, Tomoki</creatorcontrib><creatorcontrib>Hirata, Shintaro</creatorcontrib><creatorcontrib>Tsuboi, Hiroto</creatorcontrib><creatorcontrib>Sumida, Takayuki</creatorcontrib><creatorcontrib>Morimoto, Hisanori</creatorcontrib><creatorcontrib>Sato, Tomomi</creatorcontrib><creatorcontrib>Iwao, Haruka</creatorcontrib><creatorcontrib>Miki, Miyuki</creatorcontrib><creatorcontrib>Sakai, Tomoyuki</creatorcontrib><creatorcontrib>Fujita, Yoshimasa</creatorcontrib><creatorcontrib>Tanaka, Masao</creatorcontrib><creatorcontrib>Fukushima, Toshihiro</creatorcontrib><creatorcontrib>Okazaki, Toshiro</creatorcontrib><creatorcontrib>Umehara, Hisanori</creatorcontrib><title>Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>IgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.
Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.
DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.
The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity.</description><subject>Aberration</subject><subject>Abnormalities</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Allergies</subject><subject>alpha-Defensins - genetics</subject><subject>alpha-Defensins - metabolism</subject><subject>Asthma</subject><subject>Autoimmune Diseases - immunology</subject><subject>Autoimmune Diseases - pathology</subject><subject>Blood</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Charcot-Leyden crystal protein</subject><subject>Control methods</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Down-Regulation</subject><subject>Etiology</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - metabolism</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunity (Disease)</subject><subject>Immunity, Innate - genetics</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunologic deficiency syndromes</subject><subject>Immunology</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Interleukin 8</subject><subject>Interleukin 8 receptors</subject><subject>Internal medicine</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lymphocytes T</subject><subject>Lysophospholipase - genetics</subject><subject>Lysophospholipase - metabolism</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Membrane proteins</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Neutrophils</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pancreatitis</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Plasma cells</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Real time</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors</subject><subject>Receptors, Interleukin-8 - genetics</subject><subject>Receptors, Interleukin-8 - metabolism</subject><subject>Rheumatology</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Steroids</subject><subject>Th2 Cells - cytology</subject><subject>Th2 Cells - immunology</subject><subject>Therapy</subject><subject>Up-Regulation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkJw0WLHjuPcTBrdKJWGNo2PW8t1jltPiV3sBLZr_jjO2lUt2gXKReKT57zH57VPlr0keExoST5c-z441YxX3sEYk5wXIn-UHZKK5iOeY_p45_sgexbjNcYFFZw_zQ7yoiqpqOhh9ucUdAAVoUZnN6sAMVrvkDdo5pzqAM3atne2ux1dQZPWNZqCg4isQ5cQ7GoJQTXoY-N9jb54512vG1ABTaBpIjLBt-hSdRZcF9Fv2y3RbDFlW61TG4fSz7MnRjURXmzeR9n3T2ffJp9H5xfT2eTkfKR5lXcjls_n2tCcGOAUCyKq3BRCc2ZKELqqaMG0ZgpzklciBbWZK1FpxficYGwYPcper3VXjY9y41-UhAtccVLSgZitidqra7kKtlXhVnpl5V3Ah4VUobOpR1mWcwxlzZVgBSM1VYaTqgIqClCspmXSOt5U6-ct1Dp5kLzaE93_4-xSLvwvyRglguIk8G4jEPzPHmInWxt1MlY58P3dvtOpp-Md9v3mH_Th7jbUQqUGrDM-1dWDqDxhyVfMCjKUHT9ApaeG1up02YxN8b2E93sJiengpluoPkY5-3r1_-zFj3327Q67BNV0y-ibvks3NO6DbA3q4GMMYLYmEyyHWbl3Qw6zIjezktJe7R7QNul-OOhfnUEOdg</recordid><startdate>20150514</startdate><enddate>20150514</enddate><creator>Nakajima, 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Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease</title><author>Nakajima, Akio ; Masaki, Yasufumi ; Nakamura, Takuji ; Kawanami, Takafumi ; Ishigaki, Yasuhito ; Takegami, Tsutomu ; Kawano, Mitsuhiro ; Yamada, Kazunori ; Tsukamoto, Norifumi ; Matsui, Shoko ; Saeki, Takako ; Okazaki, Kazuichi ; Kamisawa, Terumi ; Miyashita, Taiichiro ; Yakushijin, Yoshihiro ; Fujikawa, Keita ; Yamamoto, Motohisa ; Hamano, Hideaki ; Origuchi, Tomoki ; Hirata, Shintaro ; Tsuboi, Hiroto ; Sumida, Takayuki ; Morimoto, Hisanori ; Sato, Tomomi ; Iwao, Haruka ; Miki, Miyuki ; Sakai, Tomoyuki ; Fujita, Yoshimasa ; Tanaka, Masao ; Fukushima, Toshihiro ; Okazaki, Toshiro ; Umehara, Hisanori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-42bbcf321fe63081892f58c64f7e8c99354cc4a0612984f7cfba89ca46b100f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aberration</topic><topic>Abnormalities</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Allergies</topic><topic>alpha-Defensins - genetics</topic><topic>alpha-Defensins - metabolism</topic><topic>Asthma</topic><topic>Autoimmune Diseases - immunology</topic><topic>Autoimmune Diseases - pathology</topic><topic>Blood</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Charcot-Leyden crystal protein</topic><topic>Control methods</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>DNA microarrays</topic><topic>Down-Regulation</topic><topic>Etiology</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - metabolism</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunity (Disease)</topic><topic>Immunity, Innate - genetics</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - blood</topic><topic>Immunologic deficiency syndromes</topic><topic>Immunology</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>Interleukin 8</topic><topic>Interleukin 8 receptors</topic><topic>Internal medicine</topic><topic>Leukocytes (mononuclear)</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Lymphocytes T</topic><topic>Lysophospholipase - genetics</topic><topic>Lysophospholipase - metabolism</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Membrane proteins</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Middle Aged</topic><topic>Neutrophils</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pancreatitis</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Peripheral blood mononuclear cells</topic><topic>Plasma cells</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Real time</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors</topic><topic>Receptors, Interleukin-8 - genetics</topic><topic>Receptors, Interleukin-8 - metabolism</topic><topic>Rheumatology</topic><topic>Ribonucleic acid</topic><topic>Risk factors</topic><topic>RNA</topic><topic>Steroids</topic><topic>Th2 Cells - cytology</topic><topic>Th2 Cells - immunology</topic><topic>Therapy</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakajima, Akio</creatorcontrib><creatorcontrib>Masaki, Yasufumi</creatorcontrib><creatorcontrib>Nakamura, Takuji</creatorcontrib><creatorcontrib>Kawanami, Takafumi</creatorcontrib><creatorcontrib>Ishigaki, Yasuhito</creatorcontrib><creatorcontrib>Takegami, Tsutomu</creatorcontrib><creatorcontrib>Kawano, Mitsuhiro</creatorcontrib><creatorcontrib>Yamada, Kazunori</creatorcontrib><creatorcontrib>Tsukamoto, Norifumi</creatorcontrib><creatorcontrib>Matsui, Shoko</creatorcontrib><creatorcontrib>Saeki, Takako</creatorcontrib><creatorcontrib>Okazaki, Kazuichi</creatorcontrib><creatorcontrib>Kamisawa, Terumi</creatorcontrib><creatorcontrib>Miyashita, Taiichiro</creatorcontrib><creatorcontrib>Yakushijin, Yoshihiro</creatorcontrib><creatorcontrib>Fujikawa, Keita</creatorcontrib><creatorcontrib>Yamamoto, Motohisa</creatorcontrib><creatorcontrib>Hamano, Hideaki</creatorcontrib><creatorcontrib>Origuchi, Tomoki</creatorcontrib><creatorcontrib>Hirata, Shintaro</creatorcontrib><creatorcontrib>Tsuboi, Hiroto</creatorcontrib><creatorcontrib>Sumida, Takayuki</creatorcontrib><creatorcontrib>Morimoto, Hisanori</creatorcontrib><creatorcontrib>Sato, Tomomi</creatorcontrib><creatorcontrib>Iwao, Haruka</creatorcontrib><creatorcontrib>Miki, Miyuki</creatorcontrib><creatorcontrib>Sakai, Tomoyuki</creatorcontrib><creatorcontrib>Fujita, Yoshimasa</creatorcontrib><creatorcontrib>Tanaka, Masao</creatorcontrib><creatorcontrib>Fukushima, Toshihiro</creatorcontrib><creatorcontrib>Okazaki, Toshiro</creatorcontrib><creatorcontrib>Umehara, Hisanori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central 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Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakajima, Akio</au><au>Masaki, Yasufumi</au><au>Nakamura, Takuji</au><au>Kawanami, Takafumi</au><au>Ishigaki, Yasuhito</au><au>Takegami, Tsutomu</au><au>Kawano, Mitsuhiro</au><au>Yamada, Kazunori</au><au>Tsukamoto, Norifumi</au><au>Matsui, Shoko</au><au>Saeki, Takako</au><au>Okazaki, Kazuichi</au><au>Kamisawa, Terumi</au><au>Miyashita, Taiichiro</au><au>Yakushijin, Yoshihiro</au><au>Fujikawa, Keita</au><au>Yamamoto, Motohisa</au><au>Hamano, Hideaki</au><au>Origuchi, Tomoki</au><au>Hirata, Shintaro</au><au>Tsuboi, Hiroto</au><au>Sumida, Takayuki</au><au>Morimoto, Hisanori</au><au>Sato, Tomomi</au><au>Iwao, Haruka</au><au>Miki, Miyuki</au><au>Sakai, Tomoyuki</au><au>Fujita, Yoshimasa</au><au>Tanaka, Masao</au><au>Fukushima, Toshihiro</au><au>Okazaki, Toshiro</au><au>Umehara, Hisanori</au><au>Esteban, Francisco J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-14</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0126582</spage><epage>e0126582</epage><pages>e0126582-e0126582</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>IgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.
Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.
DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.
The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25973893</pmid><doi>10.1371/journal.pone.0126582</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0126582-e0126582 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1680961734 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Abnormalities Adult Aged Aged, 80 and over Allergies alpha-Defensins - genetics alpha-Defensins - metabolism Asthma Autoimmune Diseases - immunology Autoimmune Diseases - pathology Blood Care and treatment Case-Control Studies Cell cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Charcot-Leyden crystal protein Control methods Cytokines Deoxyribonucleic acid Development and progression DNA DNA microarrays Down-Regulation Etiology Female Gastroenterology Gene expression Genes Genetic aspects Glycoproteins - genetics Glycoproteins - metabolism Hematology Hospitals Humans Hypersensitivity Immune system Immunity Immunity (Disease) Immunity, Innate - genetics Immunoglobulin G Immunoglobulin G - blood Immunologic deficiency syndromes Immunology Infiltration Inflammation Innate immunity Interleukin 8 Interleukin 8 receptors Internal medicine Leukocytes (mononuclear) Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Lymphocytes T Lysophospholipase - genetics Lysophospholipase - metabolism Male Medical research Medicine Membrane proteins Membrane Proteins - genetics Membrane Proteins - metabolism Middle Aged Neutrophils Oligonucleotide Array Sequence Analysis Pancreatitis Pathogenesis Patients Peripheral blood mononuclear cells Plasma cells Polymerase chain reaction Proteins Real time Real-Time Polymerase Chain Reaction Receptors Receptors, Interleukin-8 - genetics Receptors, Interleukin-8 - metabolism Rheumatology Ribonucleic acid Risk factors RNA Steroids Th2 Cells - cytology Th2 Cells - immunology Therapy Up-Regulation |
| title | Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease |
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