Sletten Gaynour B G, Halvorsen Ragnhild, Egaas Eliann, Halstensen Trond S
National Veterinary Institute, Oslo, Norway.
Pediatr Allergy Immunol. 2007 Feb;18(1):71-80. doi: 10.1111/j.1399-3038.2006.00489.x.
Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). alpha-, beta- and kappa-casein-specific IgG(1), IgG(4), IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median alpha-, beta- and kappa-casein-specific IgG(1) and IgG(4) levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG(4) and IgG(1), whereas serum IgA anti-alpha -, beta- and kappa-casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased kappa-casein-specific IgG(1) levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the alpha-, beta- and kappa-casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary alpha- and beta-casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized alpha-, beta- and kappa-casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG(1) and five- to 60-fold decrease in IgG(4) levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance.
反应性患者与耐受患者之间酪蛋白特异性免疫球蛋白（Ig）G亚类和IgA血清水平的差异，可能暗示牛奶过敏（CMA）耐受形成过程中的免疫发病机制。采用酶联免疫吸附测定（ELISA）和免疫印迹技术，比较了具有延迟胃肠道症状的临床反应性和耐受的IgE介导（n = 15）和非IgE介导（n = 14）CMA患者中α-、β-和κ-酪蛋白特异性IgG(1)、IgG(4)、IgE和IgA血清水平。临床反应性IgE介导的CMA患者（n = 9）中抗酪蛋白IgE水平中位数比耐受患者（n = 6）高140至180倍，比对照组（n = 10）高160至200倍。反应性患者中α-、β-和κ-酪蛋白特异性IgG(1)和IgG(4)水平中位数比耐受患者高9至60倍。因此，IgE介导的CMA中的临床耐受与酪蛋白特异性IgE、IgG(4)和IgG(1)降低有关，而血清IgA抗α-、β-和κ-酪蛋白水平基本未改变。与临床反应性患者相比，耐受的牛奶蛋白（CMP）敏感的特应性皮炎患者中，κ-酪蛋白特异性IgG(1)水平尤其降低。α-、β-和κ-酪蛋白特异性IgE的ELISA水平与免疫印迹相关性图谱表明，IgE介导的CMA患者主要对三级α-和β-酪蛋白表位起反应，而非IgE介导患者中的IgE对线性化的α-、β-和κ-酪蛋白表位起反应。非IgE介导的CMA患者（n = 9）中的临床耐受与酪蛋白特异性IgE水平降低4至10倍有关，同时IgG(1)降低5至8倍，IgG(4)降低5至60倍，而酪蛋白特异性IgA水平未改变。因此，两组患者的耐受特征均为对酪蛋白的体液免疫反应普遍降低，这导致了向IgA主导的功能转变。
