Predictivity of Autoimmune Stigmata for Gluten Sensitivity in Subjects with Microscopic Enteritis: A Retrospective Study

Giuseppe Losurdo, Mariabeatrice Principi, Andrea Iannone, Antonio Giangaspero, Domenico Piscitelli, Enzo Ierardi, Alfredo Di Leo, Michele Barone, Giuseppe Losurdo, Mariabeatrice Principi, Andrea Iannone, Antonio Giangaspero, Domenico Piscitelli, Enzo Ierardi, Alfredo Di Leo, Michele Barone

Abstract

Non-celiac gluten sensitivity (NCGS) is an emerging gluten-related condition. We investigated whether the presence of autoimmune stigmata in a group of patients with clinical suspicion of NCGS and a histological picture of microscopic enteritis (ME) could be a predictive factor of NCGS. Patients with ME were followed up by periodical examinations. At baseline, we collected data about previous clinical history, including autoimmune diseases. NCGS was diagnosed according to Salerno criteria; other causes of ME were diagnosed according to well-established protocols. Patients with celiac disease were excluded. Student's and chi-square tests were used in univariate analysis. Kaplan-Meier curves and Cox regression were used to estimate hazard ratios (HR). Sixty-three patients were included. Twenty-two had a final diagnosis of NCGS; the remaining 41 had non-gluten-related causes of ME. Prevalence of autoimmune thyroiditis was higher among NCGS patients (40.1%) than in other ME (14.6%; p = 0.03). NCGS showed higher positivity rate for anti-gliadin (27.3% versus 2.5%; p = 0.006) and anti-nucleus (45.4% versus 12.2%; p = 0.005). Autoimmune thyroiditis had a non-significant trend (p = 0.06) for NCGS diagnosis, (HR = 2.4). Both anti-gliadin (HR = 2.4; p = 0.04) and anti-nucleus (HR = 2.7; p = 0.04) were directly associated with NCGS diagnosis. In conclusion, NCGS may have a cohort of autoimmune stigmata that can precede its diagnosis.

Keywords: anti-gliadin; anti-nucleus antibody; autoimmunity; gluten sensitivity; thyroiditis.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart showing the process of patient selection according to inclusion and exclusion criteria. NCGS: non-celiac gluten sensitivity.
Figure 2
Figure 2
Kaplan-Meier curves showing the influence of autoimmune thyroiditis (a) or other autoimmune disorders (b) as factors predictive of NCGS development. p log rank = 0.045 for autoimmune thyroiditis and p log rank = 0.54 for other autoimmune diseases.
Figure 3
Figure 3
Kaplan-Meier curves showing the influence of AGA (a) or ANA (b) as factors predictive of NCGS development. p log rank = 0.012 for AGA and p log rank = 0.036 for ANA. AGA: anti-gliadin antibodies; ANA: anti-nucleus antibodies.
Figure 4
Figure 4
Prevalence of AGA, ANA and autoimmune thyroiditis in patients with or without DQ2-8 haplotypes. The analysis refers to the whole sample size of 63 patients.

References

    1. Fasano A., Sapone A., Zevallos V., Schuppan D. Nonceliac gluten sensitivity. Gastroenterology. 2015;148:1195–1204. doi: 10.1053/j.gastro.2014.12.049.
    1. Golley S., Corsini N., Topping D., Morell M., Mohr P. Motivations for avoiding wheat consumption in Australia: Results from a population survey. Public Health Nutr. 2015;18:490–499. doi: 10.1017/S1368980014000652.
    1. Verdu E.F., Armstrong D., Murray J.A. Between celiac disease and irritable bowel syndrome: The “no man’s land” of gluten sensitivity. Am. J. Gastroenterol. 2009;104:1587–1594. doi: 10.1038/ajg.2009.188.
    1. Peters S.L., Biesiekierski J.R., Yelland G.W., Muir J.G., Gibson P.R. Randomised clinical trial: Gluten may cause depression in subjects with non-coeliac gluten sensitivity—An exploratory clinical study. Aliment. Pharmacol. Ther. 2014;39:1104–1112. doi: 10.1111/apt.12730.
    1. Catassi C., Elli L., Bonaz B., Bouma G., Carroccio A., Castillejo G., Cellier C., Cristofori F., de Magistris L., Dolinsek J., et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The salerno experts’ criteria. Nutrients. 2015;7:4966–4977. doi: 10.3390/nu7064966.
    1. Elli L., Tomba C., Branchi F., Roncoroni L., Lombardo V., Bardella M.T., Ferretti F., Conte D., Valiante F., Fini L., et al. Evidence for the presence of Non-Celiac Gluten Sensitivity in patients with functional gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten challenge. Nutrients. 2016;8:84. doi: 10.3390/nu8020084.
    1. Villanacci V., Lanzini A., Lanzarotto F., Ricci C. Observations on the paper of Carroccio et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity. Am. J. Gastroenterol. 2013;108:619–620. doi: 10.1038/ajg.2013.22.
    1. Carroccio A., Mansueto P., Tripodo C., Florena A.M. Response to Villanacci et al. Am. J. Gastroenterol. 2013;108:620. doi: 10.1038/ajg.2013.23.
    1. Losurdo G., Piscitelli D., Pezzuto F., Fortarezza F., Covelli C., Marra A., Iannone A., Amoruso A., Principi M., Ierardi E., et al. T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity. Gastroenterol. Res. Pract. 2017;2017:5023680. doi: 10.1155/2017/5023680.
    1. Losurdo G., Piscitelli D., Di Leo A. Novel steps forward in the histopathology of non-celiac gluten sensitivity. Virchows Arch. 2018;473:525. doi: 10.1007/s00428-018-2388-z.
    1. Ierardi E., Losurdo G., Iannone A., Piscitelli D., Amoruso A., Barone M., Principi M., Pisani A., Di Leo A. Lymphocytic duodenitis or microscopic enteritis and gluten-related conditions: What needs to be explored? Ann. Gastroenterol. 2017;30:380–392. doi: 10.20524/aog.2017.0165.
    1. Sapone A., Lammers K.M., Casolaro V., Cammarota M., Giuliano M.T., De Rosa M., Stefanile R., Mazzarella G., Tolone C., Russo M.I., et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: Celiac disease and gluten sensitivity. BMC Med. 2011;9:23. doi: 10.1186/1741-7015-9-23.
    1. Sapone A., Lammers K.M., Mazzarella G., Mikhailenko I., Cartenì M., Casolaro V., Fasano A. Differential mucosal IL-17 expression in two gliadin-induced disorders: Gluten sensitivity and the autoimmune enteropathy celiac disease. Int. Arch. Allergy Immunol. 2010;152:75–80. doi: 10.1159/000260087.
    1. Uhde M., Ajamian M., Caio G., De Giorgio R., Indart A., Green P.H., Verna E.C., Volta U., Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65:1930–1937. doi: 10.1136/gutjnl-2016-311964.
    1. Carroccio A., D’Alcamo A., Cavataio F., Soresi M., Seidita A., Sciumè C., Geraci G., Iacono G., Mansueto P. High Proportions of People with Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies. Gastroenterology. 2015;149:596–603.e1. doi: 10.1053/j.gastro.2015.05.040.
    1. Rostami K., Aldulaimi D., Holmes G., Johnson M.W., Robert M., Srivastava A., Fléjou J.F., Sanders D.S., Volta U., Derakhshan M.H., et al. Microscopic enteritis: Bucharest consensus. World J. Gastroenterol. 2015;21:2593–2604. doi: 10.3748/wjg.v21.i9.2593.
    1. Moore H.M., Kelly A.B., Jewell S.D., McShane L.M., Clark D.P., Greenspan R., Hayes D.F., Hainaut P., Kim P., Mansfield E., et al. Biospecimen reporting for improved study quality (BRISQ) Cancer Cytopathol. 2011;119:92–101. doi: 10.1002/cncy.20147.
    1. Losurdo G., Piscitelli D., Giangaspero A., Principi M., Buffelli F., Giorgio F., Montenegro L., Sorrentino C., Amoruso A., Ierardi E., et al. Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up. World J. Gastroenterol. 2015;21:7545–7552. doi: 10.3748/wjg.v21.i24.7545.
    1. Ludvigsson J.F., Bai J.C., Biagi F., Card T.R., Ciacci C., Ciclitira P.J., Green P.H., Hadjivassiliou M., Holdoway A., Van Heel D.A., et al. Diagnosis and management of adult coeliac disease: Guidelines from the British Society of Gastroenterology. Gut. 2014;63:1210–1228. doi: 10.1136/gutjnl-2013-306578.
    1. Ford A.C., Moayyedi P., Lacy B.E., Lembo A.J., Saito Y.A., Schiller L.R., Soffer E.E., Spiegel B.M., Quigley E.M. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am. J. Gastroenterol. 2014;109(Suppl. 1):S2–S26. doi: 10.1038/ajg.2014.187.
    1. Ierardi E., Amoruso A., Giorgio F., Principi M., Losurdo G., Piscitelli D., Buffelli F., Fiore M.G., Mongelli A., Castellaneta N.M., et al. Mucosal molecular pattern of tissue transglutaminase and interferon gamma in suspected seronegative celiac disease at marsh 1 and 0 stages. Saudi J. Gastroenterol. 2015;21:379–385. doi: 10.4103/1319-3767.167189.
    1. Ierardi E., Losurdo G., Piscitelli D., Giorgio F., Sorrentino C., Principi M., Montenegro L., Amoruso A., Di Leo A. Seronegative celiac disease: Where is the specific setting? Gastroenterol. Hepatol. Bed Bench. 2015;8:110–116.
    1. Aziz I., Sanders D.S. The irritable bowel syndrome-celiac disease connection. Gastrointest. Endosc. Clin. N. Am. 2012;22:623–637. doi: 10.1016/j.giec.2012.07.009.
    1. Sperandeo M.P., Tosco A., Izzo V., Tucci F., Troncone R., Auricchio R., Romanos J., Trynka G., Auricchio S., Jabri B., et al. Potential celiac patients: A model of celiac disease pathogenesis. PLoS ONE. 2011;6:e21281. doi: 10.1371/journal.pone.0021281.
    1. Giorgio F., Principi M., Losurdo G., Piscitelli D., Iannone A., Barone M., Amoruso A., Ierardi E., Di Leo A. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg? Nutrients. 2015;7:7486–7504. doi: 10.3390/nu7095350.
    1. Montenegro L., Piscitelli D., Giorgio F., Covelli C., Fiore M.G., Losurdo G., Iannone A., Ierardi E., Di Leo A., Principi M. Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease. World J. Gastroenterol. 2014;20:17686–17689. doi: 10.3748/wjg.v20.i46.17686.
    1. Carroccio A., Mansueto P., D’alcamo A., Iacono G. Non-celiac wheat sensitivity as an allergic condition: Personal experience and narrative review. Am. J. Gastroenterol. 2013;108:1845–1852. doi: 10.1038/ajg.2013.353.
    1. Losurdo G., Principi M., Iannone A., Amoruso A., Ierardi E., Di Leo A., Barone M. Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm. World J. Gastroenterol. 2018;24:1521–1530. doi: 10.3748/wjg.v24.i14.1521.
    1. Philips C., Rajaguru Paramaguru D.A., Augustine P. Dermatitis Herpetiformis as the Initial Presentation of Primary Biliary Cholangitis in a Male with Gluten Sensitivity. Cureus. 2017;9:e1247. doi: 10.7759/cureus.1247.
    1. Bonciolini V., Bianchi B., Del Bianco E., Verdelli A., Caproni M. Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features. Nutrients. 2015;7:7798–7805. doi: 10.3390/nu7095368.
    1. Isasi C., Tejerina E., Morán L.M. Non-celiac gluten sensitivity and rheumatic diseases. Reumatol. Clin. 2016;12:4–10. doi: 10.1016/j.reuma.2015.03.001.
    1. Zanini B., Lanzarotto F., Villanacci V., Carabellese N., Ricci C., Lanzini A. Clinical expression of lymphocytic duodenosis in “mild enteropathy” celiac disease and in functional gastrointestinal syndromes. Scand. J. Gastroenterol. 2014;49:794–800. doi: 10.3109/00365521.2014.919017.
    1. Losurdo G., Principi M., Di Leo A., Ierardi E. Letter: Helicobacter-negative gastritis—A distinct condition? Aliment. Pharmacol. Ther. 2015;41:597–598. doi: 10.1111/apt.13080.
    1. Ianiro G., Bibbò S., Bruno G., Ricci R., Arena V., Gasbarrini A., Cammarota G. Prior Misdiagnosis of Celiac Disease Is Common among Patients Referred to a Tertiary Care Center: A Prospective Cohort Study. Clin. Transl. Gastroenterol. 2016;7:e139. doi: 10.1038/ctg.2015.48.
    1. Bibbò S., Pes G.M., Usai-Satta P., Salis R., Soro S., Colosso B.M., Dore M.P. Chronic autoimmune disorders are increased in coeliac disease: A case-control study. Medicine (Baltimore) 2017;96:e8562. doi: 10.1097/MD.0000000000008562.
    1. Freeman H.J. Endocrine manifestations in celiac disease. World J. Gastroenterol. 2016;22:8472–8479. doi: 10.3748/wjg.v22.i38.8472.
    1. Lerner A., Jeremias P., Matthias T. Gut-thyroid axis and celiac disease. Endocr. Connect. 2017;6:R52–R58. doi: 10.1530/EC-17-0021.
    1. Lerner A., Aminov R., Matthias T. Transglutaminases in dysbiosis as potential environmental drivers of autoimmunity. Front. Microbiol. 2017;8:66. doi: 10.3389/fmicb.2017.00066.
    1. Losurdo G., Principi M., Iannone A., Ierardi E., Di Leo A. The interaction between celiac disease and intestinal microbiota. J. Clin. Gastroenterol. 2016;50(Suppl. 2):S145–S147. doi: 10.1097/MCG.0000000000000682.
    1. Conti V., Leone M.C., Casato M., Nicoli M., Granata G., Carlesimo M. High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease. Eur. Ann. Allergy Clin. Immunol. 2015;47:54–57.
    1. Volta U., Tovoli F., Cicola R., Parisi C., Fabbri A., Piscaglia M., Fiorini E., Caio G. Serological tests in gluten sensitivity (nonceliac gluten intolerance) J. Clin. Gastroenterol. 2012;46:680–685. doi: 10.1097/MCG.0b013e3182372541.
    1. Losurdo G., Giorgio F., Piscitelli D., Montenegro L., Covelli C., Fiore M.G., Giangaspero A., Iannone A., Principi M., Amoruso A., et al. May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis? World J. Gastroenterol. 2016;22:8017–8025. doi: 10.3748/wjg.v22.i35.8017.
    1. Smigoc Schweiger D., Mendez A., Kunilo Jamnik S., Bratanic N., Bratina N., Battelino T., Brecelj J., Vidan-Jeras B. High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease. Autoimmunity. 2016;49:240–247. doi: 10.3109/08916934.2016.1164144.
    1. Spadaccino A.C., Basso D., Chiarelli S., Albergoni M.P., D’Odorico A., Plebani M., Pedini B., Lazzarotto F., Betterle C. Celiac disease in North Italian patients with autoimmune thyroid diseases. Autoimmunity. 2008;41:116–121. doi: 10.1080/08916930701620209.
    1. Volta U., Bardella M.T., Calabrò A., Troncone R., Corazza G.R. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med. 2014;12:85. doi: 10.1186/1741-7015-12-85.
    1. Dinu M., Macchia D., Pagliai G., Gori A.M., Cesari F., Marcucci R., Sofi F., Casini A. Symptomatic efficacy of buckwheat products in Non-Celiac Gluten Sensitivity (NCGS) Asia Pac. J. Clin. Nutr. 2017;26:630–636. doi: 10.6133/apjcn.072016.07.
    1. Sarchielli P., Alberti A., Baldi A., Coppola F., Rossi C., Pierguidi L., Floridi A., Calabresi P. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache. 2006;46:200–207. doi: 10.1111/j.1526-4610.2006.00337.x.
    1. Green P.H., Alaedini A., Sander H.W., Brannagan T., Latov N., Chin R.L. Mechanisms underlying celiac disease and its neurologic manifestations. Cell. Mol. Life Sci. 2005;62:791–799. doi: 10.1007/s00018-004-4109-9.
    1. Ierardi E., Losurdo G., Piscitelli D., Giorgio F., Amoruso A., Iannone A., Principi M., Di Leo A. Biological markers for non celiac gluten sensitivity: A question awaiting for a convincing answer. Gastroenterol. Hepatol. Bed Bench. 2018;11:203–208.
    1. Krysiak R., Szkróbka W., Okopień B. The Effect of Gluten-Free Diet on Thyroid Autoimmunity in Drug-Naïve Women with Hashimoto’s Thyroiditis: A Pilot Study. Exp. Clin. Endocrinol. Diabetes. 2018 doi: 10.1055/a-0653-7108.

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