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IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-07-03 , DOI: 10.1038/s41598-020-66981-z
Divya Thiagarajan 1 , Nina Oparina 1 , Susanna Lundström 2 , Roman Zubarev 2 , Jitong Sun 1 , , Marta Alarcon-Riquelme 1, 3 , Johan Frostegård 1
Affiliation  

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren’s syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions.



中文翻译:

在各种系统性风湿病中针对丙二醛和磷酸胆碱的IgM抗体。

抗磷酸胆碱(抗PC)和丙二醛(抗MDA)的IgM抗体在心血管和风湿性疾病中可能具有保护作用。我们在这里比较这些抗体在系统性风湿病中的情况,并研究其特性。使用ELISA对SLE(374),RA(354),混合性结缔组织病(MCTD,77),系统性硬化症(SSc,331),干燥综合征(SjS,324),原发性抗磷脂综合征(PAPs,65),未分化的结缔组织病(UCTD,118)和515匹配的健康对照(HC)。心血管评分(CV)是根据临床疾病症状广泛定义的。使用蛋白质组学从头测序方法比较了抗PC和抗MDA肽/蛋白质的特性。从总IgM中提取抗MDA和抗PC。通过流式细胞术确定Treg细胞的比例。病例与对照之间的最大差异显示为:MCTD:患者中的IgM Anti-PC显着降低,但抗MDA则没有(中位数49.3RU / ml与健康对照中的70.4,p(t-test)= 0.0037)。IgM低水平在MCTD,SLE,SjS,SSc和UCTD中更为普遍。IgM抗PC可变区谱与抗MDA不同,并且同源性更高。在整个患者组中,抗PC而非抗MDA与CV显着负相关。与IgM抗PC相比,抗MDA不会促进Treg的极化。两者合计,抗PC在MCTD以及SLE,SjS和SSc中均降低,但在其他已研究疾病中未降低。因此,抗PC可能会区分这些。相反,抗MDA并未显示所研究疾病之间的这些差异。在患者组中,抗PC水平与CV呈负相关。与抗PC相比,抗MDA不会促进Treg极化。这些发现可能具有诊断和治疗意义,一种可能性是在某些风湿病条件下使用PC主动或被动免疫。

更新日期:2020-07-03
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