Åhlin E, Elshafie A I, Nur M A M, Rönnelid J
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Scand J Immunol. 2015 Mar;81(3):201-8. doi: 10.1111/sji.12265.
African patients with Leishmania donovani infections have signs of strong systemic inflammation and high levels of circulating immune complexes (IC) and rheumatoid factor (RF), all serologic markers of rheumatic disease. As inflammation in general is associated with citrullination, we sought to investigate ACPA responses in Sudanese Leishmania patients. Serum samples were collected from Sudanese patients with visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) as well as from ACPA-positive Sudanese rheumatoid arthritis patients and compared to healthy Sudanese controls. Levels of circulating C1q-binding IC and anticyclic citrullinated peptide 2(CCP2) were investigated using ELISA, and RF was measured with nephelometry. C1q adsorption was carried out to investigate anti-CCP2 content in IC. Citrulline specificity was evaluated with control plates with cyclic arginine-containing control peptides. Leishmania-infected patients had elevated levels of RF and circulating IC but also a significant increase in anti-CCP2 (12%) as compared to healthy controls. Anti-CCP2-positive Leishmania patients displayed lower anti-CCP2 levels than Sudanese patients with rheumatoid arthritis (RA), and anti-CCP2 levels in Leishmania patients showed a continuum not resembling the dichotomous pattern seen in patients with RA. Whereas the anti-CCP reactivity of Sudanese RA sera was strictly citrulline dependent, anti-CCP2-positive Leishmania sera reacted equally well with ELISA plates containing arginine control peptides. There was a strong correlation between anti-CCP2 and circulating IC among the Leishmania patients, but IC depletion only marginally diminished anti-CCP2 levels. Our findings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions associated with macrophage activation.
患有杜氏利什曼原虫感染的非洲患者有强烈的全身炎症迹象，循环免疫复合物（IC）和类风湿因子（RF）水平较高，这些都是风湿性疾病的血清学标志物。由于一般炎症与瓜氨酸化有关，我们试图研究苏丹利什曼病患者中的抗环瓜氨酸肽抗体（ACPA）反应。从患有内脏利什曼病（VL）和黑热病后皮肤利什曼病（PKDL）的苏丹患者以及ACPA阳性的苏丹类风湿关节炎患者中采集血清样本，并与健康的苏丹对照进行比较。使用酶联免疫吸附测定法（ELISA）研究循环C1q结合IC和抗环瓜氨酸肽2（CCP2）的水平，并用比浊法测量RF。进行C1q吸附以研究IC中的抗CCP2含量。用含环精氨酸对照肽的对照板评估瓜氨酸特异性。与健康对照相比，利什曼原虫感染患者的RF和循环IC水平升高，但抗CCP2也显著增加（12%）。抗CCP2阳性的利什曼病患者的抗CCP2水平低于苏丹类风湿关节炎（RA）患者，利什曼病患者的抗CCP2水平呈现出一种连续状态，不像RA患者那样呈现二分模式。苏丹RA血清的抗CCP反应严格依赖瓜氨酸，而抗CCP2阳性的利什曼病血清与含精氨酸对照肽的ELISA板反应同样良好。利什曼病患者中抗CCP2与循环IC之间存在很强的相关性，但IC去除仅略微降低了抗CCP2水平。我们的研究结果强调，在与巨噬细胞活化相关的非风湿性疾病中进行评估时，仔细解读CCP检测阳性结果的重要性。
