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首页> 外文期刊>Allergy >Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes.
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Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes.

机译：二聚体IVIG包含天然的抗Siglec-9自身抗体及其抗独特型。

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BACKGROUND: Intravenous immunoglobulin (IVIG) preparations are increasingly used for the treatment of autoimmune and chronic inflammatory diseases. Naturally occurring autoantibodies against Siglec-9 and Fas are thought to contribute to the anti-inflammatory effects of IVIG via cell death regulation of leukocytes and tissue cells. Dimeric IVIG fractions are suspected to contain idiotypic (Id)-anti-idiotypic complexes of antibodies, which might also include anti-Siglec-9 and anti-Fas autoantibodies. METHODS: Dimeric IVIG fractions were separated from monomeric IVIG by size-exclusion chromatography and remonomerized by low pH treatment. Binding studies of total, monomeric, and dimeric IVIG were performed using surface plasmon resonance and flow cytometry on primary human neutrophils. RESULTS: Anti-Siglec-9 and anti-Fas autoantibodies were contained in both monomeric and dimeric IVIG fractions, but anti-Siglec-9 antibodies were highly enriched in dimeric IVIG. The propensity to engage in dimer formation was paratope dependent. IVIG binding to Siglec-9 was specific and sialylation independent. Interestingly, we detected anti-idiotypic antibodies (anti-Ids) against anti-Siglec-9 autoantibodies in dimeric, but not in monomeric fractions of IVIG. CONCLUSIONS: Our study supports the concept that idiotype-anti-idiotype (Id-anti-Id) interactions contribute to the dimer formation in IVIG preparations. To our knowledge, this is the first description of Id-anti-Id dimers of death receptor-specific antibodies in IVIG. Such Id-anti-Id interactions might determine the activity of immunomodulatory antibodies present both in IVIG and the patient.
机译：背景：静脉免疫球蛋白（IVIG）制剂越来越多地用于治疗自身免疫性疾病和慢性炎症性疾病。人们认为天然存在的针对Siglec-9和Fas的自身抗体可通过调节白细胞和组织细胞的细胞死亡来促进IVIG的抗炎作用。怀疑二聚体IVIG组分含有抗体的独特型（Id）-抗独特型复合物，其中还可能包含抗Siglec-9和抗Fas自身抗体。方法：通过尺寸排阻色谱法从单体IVIG中分离出二聚体IVIG馏分，并通过低pH处理使其单体化。使用表面等离振子共振和流式细胞仪对原代人中性粒细胞进行了总，单体和二聚体IVIG的结合研究。结果：单体和二聚体IVIG组分均含有抗Siglec-9和Fas自体抗体，但抗Siglec-9抗体高度富含二聚体IVIG。参与二聚体形成的倾向是依赖对位的。 IVIG与Siglec-9的结合是特异性的并且不依赖唾液酸化。有趣的是，我们在二聚体中检测到针对抗Siglec-9自身抗体的抗独特型抗体（anti-Ids），但未在IVIG的单体级分中检测到。结论：我们的研究支持独特型-抗独特型（Id-anti-Id）相互作用有助于IVIG制剂中二聚体形成的概念。据我们所知，这是IVIG中死亡受体特异性抗体的Id-anti-Id二聚体的首次描述。这种Id-抗-Id相互作用可能决定了IVIG和患者体内都存在的免疫调节抗体的活性。

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