Introduction
Diagnosis of coeliac disease (CeD) rests on clinical signs, serology (IgA against transglutaminase 2 (IgA-TG2), alternatively IgG to deamidated gliadin peptides (IgG-DGP)) and mucosal damage in duodenal biopsies [1, 2]. Mucosal pathology is often classified according to the modified Marsh criteria [3]. A gluten free diet leads to clinical, serological and mucosal improvement and rapid immunological improvement as well as mucosal healing after 1 year after rigid follow-up [4]. However, we previously reported that only ½ of treated patients in a community-based setting reached mucosal healing one year after diagnosis [5]. We here report recent results.
Aims & Methods
Patients with suspected CeD were referred from general practice to secondary care endoscopy service at Oslo University Hospital; no thertiary referral patients are reported here. All patients gave written, informed consent. Serology was repeated at the day of endoscopy. Diagnosis of CeD was given for patients with combination of positive serology and definite mucosal damage (Marsh 3a-c). Exceptions to this was agreed in selected cases after careful clinical evaluation. All participants who received the CeD diagnosis were referred to one individual consultation with a clinical dietician and to a follow-up endoscopy after 12 months. Patients with CeD in Norway receives a monthly reimbursement of approximately EUR 66 pr month to cover their additional costs for a gluten-free diet.
Results
In total 138 of the 214 eligible participants were diagnosed with CeD between 2018 and 2021. Among these, 6 patients had negative (<4 U/L) IgA-TG2, 29 a negative (<20 U/L) IgG-DGP and only 2 were seronegative for both markers. Correlation between levels of igA-TG2 and IgG-DGP were calculated with Pearson (assuming normal distribution) showing a correlation coefficient (r) = 0.4893, p-verdi =0.0000112, i.e. a significant moderate positive correlation. Spearman's rank correlation coefficient (rs) = 0.52095, p-verdi = 0.000002301 showed signficant strong positive correlation (assuming not normal distribution). Within the CeD group, 63 were diagnosed with a Marsh 3C, 44 with Marsh 3B, 22 with Marsh 3A, and 9 with Marsh 1 or 2. One hundred and four patients came to the 1-year control. Eighty had achieved mucosal healing (Marsh 0 or 1), while 19 showed improvement but still showed mucosal damage (Marsh 3). Nine of the patients who did not achieve mucosal healing were followed up for an additional year where 6 achieved recovery. Thus, only 3 could be classified as non-responsive CeD. No data are available for those who did not return to repeated endoscopy.
Conclusion
Simultaneous testing of both IgA-TG2 and IgG-DGP renders very few patients truly seronegative, as only 2 of 139 new CeD patients were negative for both. Wide ranges were seen for both IgA-TG2 and IgG-DGP. We now investigate factors in serum leading to predominant IgA-TG2 vs IgG-DGP responses using multi-plex inflammation panel analysis. One year after the diagnosis, and with the mentioned follow-up system, the prognosis for mucosal healing is achieved in 77% of patients and better than often anticipated.
References
1. Al-Toma, A., et al., European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J, 2019. 7(5): p. 583-613.
2. Rubio-Tapia, A., et al., American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol, 2023. 118(1): p. 59-76.
3. Oberhuber, G., G. Granditsch, and H. Vogelsang, The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol, 1999. 11(10): p. 1185-94.
4. Risnes, L.F., et al., Gluten-free diet induces rapid changes in phenotype and survival properties of gluten-specific T cells in celiac disease. Gastroenterology, 2024.
5. Haere, P., et al., Long-term mucosal recovery and healing in celiac disease is the rule - not the exception. Scand J Gastroenterol, 2016. 51(12): p. 1439-1446.