A 21‐bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course

• Published in: Journal of the peripheral nervous system Vol. 29; no. 2; pp. 193 - 201
• Main Authors: Bos, Jeroen W., Groen, Ewout J. N., Otten, Henny G., Budding, Kevin, Eijk, Ruben P. A., Curial, Chantall, Kardol‐Hoefnagel, Tineke, Goedee, H. Stephan, Berg, Leonard H., Pol, W. Ludo
• Format: Journal Article
• Language: English
• Published: Malden, USA Wiley Periodicals, Inc 01.06.2024; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; CD46 antigen; CD55; CD55 Antigens - genetics; CD59 antigen; CD59 Antigens - genetics; Complement activation; Complement component C5; Complement system; DAF; Disease Progression; Female; Gene polymorphism; genetics; Genotype; Genotype & phenotype; Humans; Inflammation; Male; Medical research; Membrane Cofactor Protein - genetics; Middle Aged; multifocal motor neuropathy; Patients; Polyneuropathies - genetics; Polyneuropathies - immunology; Polyneuropathies - physiopathology; Progressive motor neuropathy; Promoter Regions, Genetic; Sequence Deletion; DAF; genetics; multifocal motor neuropathy; complement system; CD55
• ISSN: 1085-9489; 1529-8027; 1529-8027
• DOI: 10.1111/jns.12620

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.