Calenoff Emanuel
Enteron, Inc., 7030 Lattimore Drive, Dallas, TX 75252, USA.
ISRN Neurol. 2012;2012:851541. doi: 10.5402/2012/851541. Epub 2012 Jan 23.
The author hypothesized that multiple sclerosis (MS) is a humoral autoimmune disease, caused by faulty interplay between myelin-specific, dimeric IgE, specifically competing non-IgE antibodies and IgE-triggered degranulating mast cells. The principal fault was believed to be insufficient quantity of protective, specific non-IgE antibodies. Also conjectured was the possibility of an unexpected and adverse immune suppression caused by none-MS pharmaceuticals being consumed by patients for their MS or for other conditions. To test both hypotheses, a mimotopic, peptide antigen-based, serum immunoassay was developed to measure dimer-bound IgE excess among MS patients, wherein the IgE specifically complexes with two or more myelin surface epitopes at an interval of 40-100 Angstroms, a separation critical for mast cell degranulation and cell damaging effect. MS test sensitivity and specificity, when analyzing five previously untreated patients for dimeric IgE presence, was 100%. In direct comparison, twenty age- and gender-matched female and male control subjects were test negative. Analysis of 35 multiple sclerosis patients, who were concomitantly being treated with potentially immunosuppressive pharmaceuticals, appeared to show the substances' negative effect upon MS causation, progression, or specific immunoassay performance. Therefore, MS is likely an autoimmune disease caused by IgE-mediated mast cell degranulation possibly in conjunction with immunosuppressive agents.
作者推测,多发性硬化症(MS)是一种体液自身免疫性疾病,由髓鞘特异性二聚体IgE、特异性竞争非IgE抗体和IgE触发的脱颗粒肥大细胞之间的相互作用异常所致。主要缺陷被认为是保护性特异性非IgE抗体数量不足。还推测了患者因MS或其他病症服用非MS药物而导致意外和不良免疫抑制的可能性。为了验证这两个假设,开发了一种基于模拟表位肽抗原的血清免疫测定法,以测量MS患者中二聚体结合IgE的过量情况,其中IgE与两个或更多髓鞘表面表位特异性结合,间隔为40-100埃,这种间隔对肥大细胞脱颗粒和细胞损伤作用至关重要。在分析五名先前未接受治疗的患者是否存在二聚体IgE时,MS检测的敏感性和特异性为100%。直接比较显示,二十名年龄和性别匹配的男性和女性对照受试者检测为阴性。对35名同时接受潜在免疫抑制药物治疗的多发性硬化症患者的分析似乎表明,这些物质对MS的病因、进展或特异性免疫测定性能有负面影响。因此,MS可能是一种由IgE介导的肥大细胞脱颗粒引起的自身免疫性疾病,可能与免疫抑制剂有关。