Arbuckle M R, Gross T, Scofield R H, Hinshaw L B, Chang A C, Taylor F B, Harley J B, James J A
University of Oklahoma Health Sciences Center, USA.
J Investig Med. 1998 Feb;46(2):58-65.
Systemic lupus erythematosus (SLE) is characterized by humoral autoimmunity against the spliceosomal proteins, including Sm B/B'. In SLE patients with anti-Sm B/B' antibodies the proline rich sequence, PPPGMRPP, is the predominant Sm B/B' autoimmune epitope and appears to be an early target in the development of the anti-Sm B/B' response.
Two female baboons were immunized with the PPPGMRPP peptide from the Sm B/B' spliceosomal protein constructed on a MAP backbone in Freund's adjuvant. One female control baboon was immunized with Freund's adjuvant alone. Baboon sera were collected and assessed for antibody binding to the spliceosomal proteins and compared to SLE patient and control sera.
Peptide immunized baboons developed antibodies to multiple regions of the Sm B/B' protein, as well as reactivity against other spliceosomal proteins. Consistent with serologic manifestations found in SLE, experimental baboons also acquired anti-nuclear antibodies, anti-nuclear ribonucleoprotein (nRNP) antibodies and, in one animal, anti-double stranded DNA antibodies. The control animal had none of these immunologic findings.
Immunization with PPPGMRPP is capable of initiating a humoral autoimmune response in primates against the Sm, nRNP complex from which the peptide was derived. The additional autoantibody specificities generated in experimental animals are similar to those found in human SLE sera. This study is the first evidence of peptide induction of SLE humoral autoimmunity in a primate model.
系统性红斑狼疮（SLE）的特征是针对包括Sm B/B'在内的剪接体蛋白的体液自身免疫。在具有抗Sm B/B'抗体的SLE患者中，富含脯氨酸的序列PPPGMRPP是主要的Sm B/B'自身免疫表位，并且似乎是抗Sm B/B'反应发展中的早期靶点。
用在弗氏佐剂中构建于MAP骨架上的Sm B/B'剪接体蛋白的PPPGMRPP肽免疫两只雌性狒狒。一只雌性对照狒狒仅用弗氏佐剂免疫。收集狒狒血清并评估其与剪接体蛋白的抗体结合情况，并与SLE患者和对照血清进行比较。
肽免疫的狒狒产生了针对Sm B/B'蛋白多个区域的抗体，以及针对其他剪接体蛋白的反应性。与SLE中发现的血清学表现一致，实验狒狒还获得了抗核抗体、抗核糖核蛋白（nRNP）抗体，并且在一只动物中获得了抗双链DNA抗体。对照动物没有这些免疫学发现。
用PPPGMRPP免疫能够在灵长类动物中引发针对该肽所源自的Sm、nRNP复合物的体液自身免疫反应。实验动物中产生的额外自身抗体特异性与人类SLE血清中发现的相似。本研究是在灵长类动物模型中肽诱导SLE体液自身免疫的首个证据。
