Clinical features of Sjogren's syndrome patients with autoantibodies against interferons

被引:15
作者
Burbelo, Peter D. [1 ]
Browne, Sarah [2 ]
Holland, Steve M. [2 ]
Iadarola, Michael J. [3 ]
Alevizos, Ilias [4 ]
机构
[1] NIDCR, Dent Clin Res Core, NIH, Bldg 10,Room 5N106,10 Ctr Dr, Bethesda, MD 20892 USA
[2] NIAID, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIH, Perioperat & Pain Sect, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA
[4] NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, NIH, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
Anticytokine autoantibodies; Autoantibodies; Autoimmunization; Interferon-alpha autoantibodies; Sjogren's syndrome; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; ANTI-CYTOKINE AUTOANTIBODIES; GM-CSF AUTOANTIBODIES; ANTICYTOKINE AUTOANTIBODIES; DISEASE-ACTIVITY; ALPHA; ACTIVATION; ANTIBODIES; IDENTIFICATION;
D O I
10.1186/s40169-018-0218-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundSjogren's syndrome (SS) is an autoimmune disease characterized by immune attack on the salivary and lacrimal glands. Given the known cytokine activation and type I interferon gene expression signature found in SS, we hypothesized that anticytokine autoantibodies might be detectable by Luciferase immunoprecipitation systems in some SS patients and correlate with clinical symptoms.ResultsLuciferase immunoprecipitation systems was used to screen for serum anti-cytokine autoantibodies in 57 primary SS patients and 25 healthy volunteers. Autoantibodies were detected against GMCSF, interferon-, - and, - in one, two, two and six patients with SS, respectively. None of the healthy volunteers showed anticytokine autoantibodies and none of the SS or control subjects showed autoantibodies against interferon-. One 51-year old female SS subject with the highest anti-interferon- and - autoantibody levels had stable autoantibody levels over the course of a year. In vitro functional testing of serum autoantibodies from this subject demonstrated partially neutralizing activity for interferon- signaling. Clinical information on this individual revealed a low focus score and high levels of unstimulated salivary flow, suggesting the possibility that interferon- autoantibody neutralizing activity may have contributed to the milder sicca symptoms.ConclusionOverall, these findings demonstrate that a subset of SS patients (16%) harbor autoantibodies against GMCSF, interferon-, interferon-, and interferon-. These data support the observation that high levels of interferon- autoantibodies may attenuate disease symptoms in SS.
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页数:9
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共 52 条
[1]   Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus [J].
Baechler, EC ;
Batliwalla, FM ;
Karypis, G ;
Gaffney, PM ;
Ortmann, WA ;
Espe, KJ ;
Shark, KB ;
Grande, WJ ;
Hughes, KM ;
Kapur, V ;
Gregersen, PK ;
Behrens, TW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2610-2615
[2]   Anticytokine autoantibodies in infection and inflammation: an update [J].
Barcenas-Morales, Gabriela ;
Jandus, Peter ;
Doeffinger, Rainer .
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2016, 16 (06) :523-529
[3]   Activation of the type I interferon system in primary Sjogren's syndrome -: A possible etiopathogenic mechanism [J].
Båve, U ;
Nordmark, G ;
Lövgren, T ;
Rönnelid, J ;
Cajander, S ;
Eloranta, ML ;
Alm, GV ;
Rönnblom, L .
ARTHRITIS AND RHEUMATISM, 2005, 52 (04) :1185-1195
[4]   Anti-cytokine autoantibodies in postherpetic neuralgia [J].
Bayat, Ahmad ;
Burbelo, Peter D. ;
Browne, Sarah K. ;
Quinlivan, Mark ;
Martinez, Bianca ;
Holland, Steven M. ;
Buvanendran, Asokumar ;
Kroin, Jeffrey S. ;
Mannes, Andrew J. ;
Breuer, Judith ;
Cohen, Jeffrey I. ;
Iadarola, Michael J. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2015, 13
[5]   Human interferons alpha, beta and omega [J].
Bekisz, J ;
Schmeisser, H ;
Hernandez, J ;
Goldman, ND ;
Zoon, KC .
GROWTH FACTORS, 2004, 22 (04) :243-251
[6]   Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies [J].
Bengtsson, AA ;
Sturfelt, G ;
Truedsson, L ;
Blomberg, J ;
Alm, G ;
Vallin, H ;
Rönnblom, L .
LUPUS, 2000, 9 (09) :664-671
[7]   Interferon and granulopoiesis signatures in systemic lupus erythematosus blood [J].
Bennett, L ;
Palucka, AK ;
Arce, E ;
Cantrell, V ;
Borvak, J ;
Banchereau, J ;
Pascual, V .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) :711-723
[8]   IL-22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model [J].
Bichele, Rudolf ;
Karner, Jaanika ;
Truusalu, Kai ;
Smidt, Imbi ;
Mandar, Reet ;
Conti, Heather R. ;
Gaffen, Sarah L. ;
Peterson, Part ;
Laan, Martti ;
Kisand, Kai .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2018, 48 (03) :464-470
[9]   Anticytokine Autoantibody-Associated Immunodeficiency [J].
Browne, Sarah K. .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 32, 2014, 32 :635-657
[10]   Adult-Onset Immunodeficiency in Thailand and Taiwan [J].
Browne, Sarah K. ;
Burbelo, Peter D. ;
Chetchotisakd, Ploenchan ;
Suputtamongkol, Yupin ;
Kiertiburanakul, Sasisopin ;
Shaw, Pamela A. ;
Kirk, Jennifer L. ;
Jutivorakool, Kamonwan ;
Zaman, Rifat ;
Ding, Li ;
Hsu, Amy P. ;
Patel, Smita Y. ;
Olivier, Kenneth N. ;
Lulitanond, Viraphong ;
Mootsikapun, Piroon ;
Anunnatsiri, Siriluck ;
Angkasekwinai, Nasikarn ;
Sathapatayavongs, Boonmee ;
Hsueh, Po-Ren ;
Shieh, Chi-Chang ;
Brown, Margaret R. ;
Thongnoppakhun, Wanna ;
Claypool, Reginald ;
Sampaio, Elizabeth P. ;
Thepthai, Charin ;
Waywa, Duangdao ;
Dacombe, Camilla ;
Reizes, Yona ;
Zelazny, Adrian M. ;
Saleeb, Paul ;
Rosen, Lindsey B. ;
Mo, Allen ;
Iadarola, Michael ;
Holland, Steven M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (08) :725-734