TY - JOUR
T1 - A 21-bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course
AU - Bos, Jeroen W.
AU - Groen, Ewout J.N.
AU - Otten, Henny G.
AU - Budding, Kevin
AU - van Eijk, Ruben P.A.
AU - Curial, Chantall
AU - Kardol-Hoefnagel, Tineke
AU - Goedee, H. Stephan
AU - van den Berg, Leonard H.
AU - van der Pol, W. Ludo
N1 - Publisher Copyright:
© 2024 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - CD55
KW - complement system
KW - DAF
KW - genetics
KW - multifocal motor neuropathy
UR - http://www.scopus.com/inward/record.url?scp=85189369330&partnerID=8YFLogxK
U2 - 10.1111/jns.12620
DO - 10.1111/jns.12620
M3 - Article
C2 - 38528725
AN - SCOPUS:85189369330
SN - 1085-9489
VL - 29
SP - 193
EP - 201
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
IS - 2
ER -