A Broad Panel of Autoantibodies in Patients With Celiac Disease and Crohn’s Disease To the Editor: Autoimmunity and genetic predis- position are the 2 most important factors in the pathogenesis of Crohn’s disease (CD) and Celiac disease (CeD). This concept is based on several observations, including the presence of autoantibodies and immunological interactions between bacterial endotoxins and the host im- mune system. 1 Ultimately, for CeD and CD, 2 research is conducted only with those autoantibodies considered as mar- kers of the disease, or with a limited number of autoantibodies, or yet aiming just the direct association with a single disorder. In this context, the evaluation of autoantibodies using a broad range of assays can allow the detection of auto- immune diseases (AIDs) before, during, or after the diagnosis of CeD and CD. 3 Eighty-one patients were investi- gated for the presence of autoantibodies and AIDs: 45 celiacs (35 females, 10 males, age range 18 to 66 y, median 39.2 y), among them, 30 were recently diagnosed (CeD DX) and 15 were on a gluten-free diet (CeD GFD), with more than 1 year of treatment and 36 patients with CD (23 female, 13 male, age range 16 to 83 y, median 42.9 y) that fulfilled the diagnostic criteria for both diseases. The autoantibodies antimitochon- drial (AMA), smooth muscle (SMA), liver-kidney microsomal (LKM), nuclear (ANA), gastric parietal cell (GPCA), neutrophyl cytoplasmic (ANCA), and antiendomysial (EmA-IgA) were deter- mined by indirect immunofluorescence; antithyroperoxidase (anti-TPO) by im- munometric method, whereas antitissue transglutaminase (anti-tTG) and anti- Saccharomyces cerevisiae (ASCA) were evaluated by immunoenzymatic assay. Fisher exact test with Bonferroni correc- tion was used (P<0.017). The frequency of findings in CeD DX, CeD GFD, and CD were, respectively: EmA-IgA 100%, 33.3%, and 0% (P = 0.001); anti-tTG 90%, 26.7%, and 11.1% (P<0.001); ASCA IgA 66.7%, 20%, and 36.1% (P = 0.004 CeD DX vs. CeD GFD); ASCA IgG 86.7%, 66.7%, and 44.4% (P = 0.0001; CeD DX vs. DC); ANCA 0%, 0%, and 5.6%; SMA 3.3%, 13.3%, and 0%; ANA 6.7%, 6.7%, and 8.3%; GPCA 0%, 6.7%, and 0%; AMA and LKM were negative in all samples. Anti- TPO was positive in 17.6% (3/17), 50% (2/4), and 75% (6/8). Concomitant AIDs clinical associations in CeD were derma- titis herpetiformis, diabetes mellitus, and thyroid disease; in CD, psoriasis, and thyroid disease (TD). Interestingly, an association between single or multiple AIDs, and increased age of the patients for all the groups were observed. The demographic data of the studied patients showed that there was a young adult female preponderance. All celiac patients newly diagnosed presented IgA-EmA positive in contrast to patients with a GFD (33.3%), of which 5 declared that they were not adherent to a rigid diet. 4 In contrast, all the patients with CD were negative for IgA-EmA. IgA anti-tTG was positive in 90.0% of the CeD patients at diagnosis, in 26.7% of those with GFD, and in 11.1% of CD patients. The last finding is probably due to the transglutaminase to be a multifunctional enzyme present in cells of several tissues, including situations in which there is mucosal injury, 5 and corroborates re- ports showing anti-tTG positive in other gastrointestinal disorders. 6 ASCA IgA was detected in 36.1% and ASCA IgG in 44.4% of CD patients. However, ASCA IgA was positive in 66.7% and ASCA IgG in 86.7% of the CeD DX patients, probably due to increased permeability of the intestinal mucosa in these patients. 7 Interestingly, in patients with GFD, ASCA IgA was found in significantly less individuals (20.0%, P =0.004), suggesting recovery of the mucosal le- sions. ASCA IgG was detected in 66.7% of the same group, maybe due to the maintenance of memorial IgG, even with decreased IgA. Thus, ASCA did not differentiate CD from CeD in the studied individuals. Among CD patients, 5.6% were ANCA positive, in contrast to the celiac patients (0%). Although some patients (irrespective of groups) were positive for the autoantibodies (SMA, ANA, GPCA, LKM, and AMA), no clinical correlations were found till the moment. Despite the small number of samples evaluated, anti-TPO was positive in celiacs, mainly in females and older patients. In a previous study, Kotze et al 8 reported 43.3% of TD in Brazilian patients with CeD. Although the association between CD and auto- immune TD is considered rare, 2 8 pati- ents in our study presented clinical complaints typical of TD, and 6 of them were anti-TPO positive, emphasizing the importance of this determination in CD patients. The detection of autoantibodies in patients with CD may be considered as a pioneer work in the population from Southern Brazil. These data allow us to suggest that the presence of gluten could not be considered the major risk factor in the high prevalence of autoantibodies in CeD, and that even patients adhering to a GFD should be evaluated for the presence of autoantibodies. Recent re- ports reinforce the role of the intestinal barrier function and the genetical and environmental factors involved in the pathogenesis of AIDs. 9,10 In conclusion, the authors em- phasize the value of the investigating autoimmune disorders in CeD and CD patients, and a long-term follow-up of them. Petra Mirella Theiss, MSc* Lorete Maria da Silva Kotze, MD, PhD, FACG* Shirley Ramos da Rosa Utiyama, PhDw Renato Mitsunori Nisihara, MScw Isabela Goldner Silva, MScw Paulo Gustavo Kotze, MD* Ma´rcia Olandoski, MScz *Services of Gastroenterology and Coloproctology Cajuru Hospital wLaboratory of Immunopathology Clinical Hospital, Federal University of Parana` zDepartment of Statistics Pontifical Catholic University of Parana´ Curitiba Parana`, Brazil REFERENCES 1. Das KM. Relationship of extraintestinal involvements in inflammatory bowel dis- ease. New insights into autoimmune patho- genesis. Dig Dis Sci. 1999;44:1–13. 2. Inokuchi T, Moriwaki Y, Takahashi S, et al. Autoimmune thyroid disease (Grave’s disease and Hashimoto’s thyroiditis) in two patients with Crohn’s disease: case reports and literature review. Intern Med. 2005;44: 303–306. 3. Utiyama SRR, Kotze LM, Nisihara RM, et al. Spectrum of autoantibodies in celiac patients and relatives. Dig Dis Sci. 2001; 46:2623–2630. 4. Kotze LM, Utiyama SRR, Nisihara RM, et al. Antiendomysium antibodies in Brazilian patients with celiac disease and their first-degree relatives. Arq Gastroen- terol. 2001;38:94–103 5. Di Tola M, Sabbatella L, Anania MC, et al. Anti-tissue transglutaminase anti- bodies in inflammatory bowel disease: new evidence. Clin Chem Lab Med 2004;42: 1092–1097. The authors declare that they do not have any financial support or relationships that may pose conflict of interest. J Clin Gastroenterol  Volume 44, Number 4, April 2010 Letters to the Editor r 2010 Lippincott Williams & Wilkins www.jcge.com | 309