Hvatum M, Kanerud L, Hällgren R, Brandtzaeg P
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway.
Gut. 2006 Sep;55(9):1240-7. doi: 10.1136/gut.2005.076901. Epub 2006 Feb 16.
Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response.
IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow's milk (alpha-lactalbumin, beta-lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat.
In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against beta-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein. Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate.
The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.
类风湿关节炎(RA)患者常感觉食物摄入与类风湿疾病严重程度之间存在关联。为研究肠道免疫与RA之间可能存在的免疫联系,对RA患者和健康对照者空肠的血清及灌注液中的食物抗体进行检测,以确定全身和黏膜免疫反应。
检测了14例RA患者和20例健康受试者血清及空肠灌注液中针对饮食抗原的IgG、IgA和IgM抗体。抗原来源于牛奶(α-乳白蛋白、β-乳球蛋白、酪蛋白)、谷物、鸡蛋(卵清蛋白)、鳕鱼和猪肉。
许多RA患者的肠液中,所有三种免疫球蛋白类别的食物特异性活性均升高。除针对β-乳球蛋白的IgM活性外,所有其他IgM活性均显著升高,与总IgM水平无关。与RA相关的血清IgM抗体反应相对不那么明显。与IgM相比,肠道IgA活性升高不太一致,针对麦醇溶蛋白和酪蛋白无显著增加。吸收试验证明了IgM和IgA抗体有相当程度的交叉反应性。尽管肠道中针对食物的IgG活性相当低,但在RA患者中针对许多抗原仍显著升高。5例接受柳氮磺胺吡啶治疗16周的RA患者中有3例最初肠道食物抗体水平升高;治疗后这些水平恢复正常,但临床改善在红细胞沉降率降低方面体现得更好。
许多RA患者肠道中交叉反应性抗体的产生显著增加。他们与食物相关的问题可能反映了多种适度超敏反应的不良叠加效应,例如由免疫复合物介导,促进关节中的自身免疫反应。