Dore Maria Pina, Pes Giovanni Mario, Dettori Ivana, Villanacci Vincenzo, Manca Alessandra, Realdi Giuseppe
Internal Medicine Section, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Baylor College of Medicine, Michael E. DeBakey VAMC, Houston, TX, USA.
BMJ Open Gastroenterol. 2017 Jul 17;4(1):e000159. doi: 10.1136/bmjgast-2017-000159. eCollection 2017.
Patients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD.
patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA-DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available.
48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA-DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72-192).
Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.
具有乳糜泻（CD）临床、遗传和组织学特征但血清学标志物阴性的患者带来了重大临床问题。本研究的目的是勾勒出特定特征，并评估血清阴性CD患者的自然病史以及对无麸质饮食（GFD）的反应。
十二指肠黏膜损伤处于马什I、II和III期、具有HLA DQ2/DQ8单倍型且有提示CD的临床特征但CD血清学阴性的患者被定义为血清阴性CD患者。排除十二指肠黏膜损伤的其他常见原因。比较血清阴性和血清阳性CD患者所有马什分期之间的HLA-DR和DQ基因型/单倍型。在进行GFD和麸质激发试验后评估临床特征、实验室检查和组织学结果。有较长的随访期。
4年期间有48例患者符合诊断标准。血清阴性和血清阳性CD患者的临床表型以及HLA-DR和DQ频率相似。然而，马什I期在血清阴性患者中更常见（42%对22%；p<0.05）。经过1年的GFD试验，40例患者的临床症状、组织学特征和实验室检查有所改善，而在接受6个月麸质激发试验的患者中则恶化。5例血清阴性CD患者（25%）在中位随访133个月（范围72 - 192个月）期间出现了自身免疫性疾病。
血清阴性CD患者未表现出特定特征。他们与血清阳性CD患者一样从GFD中获益。在等待更敏感的血清学标志物出现之前，血清阴性CD的诊断仍然是排除性诊断。
