Jeroen W. Bos, Ewout J. N. Groen, Henny G. Otten, Kevin Budding, Ruben P. A. van Eijk, Chantall Curial, Tineke Kardol-Hoefnagel, H. Stephan Goedee, Leonard H. van den Berg, W. Ludo van der Pol
{"title":"补体调节因子 CD55 启动子区域的 21-bp 缺失与多灶性运动神经病变及其病程有关。","authors":"Jeroen W. Bos, Ewout J. N. Groen, Henny G. Otten, Kevin Budding, Ruben P. A. van Eijk, Chantall Curial, Tineke Kardol-Hoefnagel, H. Stephan Goedee, Leonard H. van den Berg, W. Ludo van der Pol","doi":"10.1111/jns.12620","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of <i>CD46</i>, <i>CD55</i>, and <i>CD59</i> in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The genotype frequencies of rs28371582, a 21-bp deletion in the <i>CD55</i> promotor region, were altered in patients with MMN as compared to controls (<i>p</i> .009; Del/Del genotype 16.8% vs. 7.7%, <i>p</i> .005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, <i>p</i> .019). The presence of <i>CD59</i> rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, <i>p</i> .032).</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>MMN susceptibility is associated with a 21-bp deletion in the <i>CD55</i> promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.</p>\n </section>\n </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"193-201"},"PeriodicalIF":3.9000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12620","citationCount":"0","resultStr":"{\"title\":\"A 21-bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course\",\"authors\":\"Jeroen W. Bos, Ewout J. N. Groen, Henny G. Otten, Kevin Budding, Ruben P. A. van Eijk, Chantall Curial, Tineke Kardol-Hoefnagel, H. Stephan Goedee, Leonard H. van den Berg, W. Ludo van der Pol\",\"doi\":\"10.1111/jns.12620\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and Aims</h3>\\n \\n <p>To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of <i>CD46</i>, <i>CD55</i>, and <i>CD59</i> in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The genotype frequencies of rs28371582, a 21-bp deletion in the <i>CD55</i> promotor region, were altered in patients with MMN as compared to controls (<i>p</i> .009; Del/Del genotype 16.8% vs. 7.7%, <i>p</i> .005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, <i>p</i> .019). The presence of <i>CD59</i> rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, <i>p</i> .032).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Interpretation</h3>\\n \\n <p>MMN susceptibility is associated with a 21-bp deletion in the <i>CD55</i> promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.</p>\\n </section>\\n </div>\",\"PeriodicalId\":17451,\"journal\":{\"name\":\"Journal of the Peripheral Nervous System\",\"volume\":\"29 2\",\"pages\":\"193-201\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-03-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12620\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Peripheral Nervous System\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jns.12620\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Peripheral Nervous System","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jns.12620","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
A 21-bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course
Background and Aims
To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.
Methods
We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.
Results
The genotype frequencies of rs28371582, a 21-bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p .009; Del/Del genotype 16.8% vs. 7.7%, p .005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, p .019). The presence of CD59 rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, p .032).
Interpretation
MMN susceptibility is associated with a 21-bp deletion in the CD55 promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.
期刊介绍:
The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders.
The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies.
Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials.
The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.