Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, the Netherlands.
Department of Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Arthritis Res Ther. 2023 Mar 8;25(1):37. doi: 10.1186/s13075-023-03009-7.
Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents.
Anti-carbamylated (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (anti-AcVim) IgG were determined in anti-citrullinated protein antibody-positive Dutch (NL, n = 103), Japanese (JP, n = 174), First Nations Peoples in Canada (FN, n = 100), and black South African (SA, n = 67) RA patients. Ethnicity-matched local healthy controls were used to calculate cut-offs. Risk factors associated with AMPA seropositivity in each cohort were identified using logistic regression.
Median AMPA levels were higher in First Nations Peoples in Canada and especially South African patients, as reflected by percentage seropositivity: NL, JP, FN, and SA: anti-CarP: 47%, 43%, 58%, and 76% (p < 0.001); anti-MAA: 29%, 22%, 29%, and 53% (p < 0.001); and anti-AcVim: 20%, 17%, 38%, and 28% (p < 0.001). Total IgG levels also differed markedly, and when autoantibody levels were normalized to total IgG, differences between cohorts became less pronounced. Although there were some associations with AMPA and HLA risk alleles and smoking, none was consistent across all four cohorts.
AMPA against various post-translational modifications could consistently be detected on different continents across ethnically diverse RA populations. Differences in AMPA levels corresponded to differences in total serum IgG levels. This suggests that, despite differences in risk factors, a common pathway may be involved in AMPA development across geographic locations and ethnicities.
类风湿关节炎（RA）在全球不同种族人群中发生。大多数 RA 患者存在抗修饰蛋白抗体（AMPA）；然而，在不同地理位置和不同种族群体之间，自身抗体反应是否存在差异，这可能为自身抗体产生的潜在因素提供新的线索，目前尚不清楚。因此，我们在四大洲的四个不同种族群体中调查了 AMPA 的流行情况以及与 HLA-DRB1 等位基因和吸烟的关联。
在荷兰（NL，n=103）、日本（JP，n=174）、加拿大第一民族（FN，n=100）和南非黑人（SA，n=67）的抗瓜氨酸化蛋白抗体阳性 RA 患者中，测定了抗氨甲酰化（抗-CarP）、抗丙二醛乙醛（抗-MAA）和抗乙酰化蛋白抗体（抗-AcVim）IgG。使用当地匹配的健康对照者来计算截断值。使用逻辑回归确定每个队列中与 AMPA 血清阳性相关的危险因素。
加拿大第一民族人和南非患者的 AMPA 水平中位数更高，反映在血清阳性率上：NL、JP、FN 和 SA：抗-CarP：47%、43%、58%和 76%（p<0.001）；抗-MAA：29%、22%、29%和 53%（p<0.001）；抗-AcVim：20%、17%、38%和 28%（p<0.001）。总 IgG 水平也有明显差异，当将自身抗体水平与总 IgG 进行归一化时，队列之间的差异变得不那么明显。尽管 AMPA 与 HLA 风险等位基因和吸烟存在一些关联，但在所有四个队列中都不一致。
在不同种族的 RA 人群中，跨越不同大陆，始终可以检测到针对各种翻译后修饰的 AMPA。AMPA 水平的差异与总血清 IgG 水平的差异相对应。这表明，尽管存在危险因素差异，但在地理位置和种族之间，AMPA 的产生可能涉及共同途径。
