Aim: In our study we explored a possible relationship between PTX3 and CD.
Background: Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity.
Methods: 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3.
Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform.
Results: PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3.31± 1.27 ng/mL and 3.97 ± 0.54 ng/mL versus 1.06 ± 0.59 ng/mL; P < 0.005), with group 1 (0.76±0.31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0.78, P <0.0001), and group 3 (r =0.63, P < 0.005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0.04; group 3, r=0.24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients.
Conclusion: PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response.
Keywords: Gluten-sensitivity, Innate immune response, Adaptive immune response, Pentraxin 3, Antigliadin antibodies, Celiac disease.
(Please cite as: Assandri R, Montanelli A. Pentraxin 3 and biopsy status in celiac patients. Gastroenterol Hepatol Bed Bench 2018;11(3):225-232).
Catassi C, Fasano A: Celiac disease. Curr Opin Gastroenterol 2008, 24:687-691.
Wolters VM, Wijmenga C: Genetic background of celiac disease and its clinical implications. Am J Gastroenterol 2008,
Hunt KA, Zhemakowa A, et al. : Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 2008, 40:395-402.
Leffl er DA , Schuppan D . Update on serologic testing in celiac disease . Am J Gastroenterol 2010 ; 105 : 2520 – 4 .
Wang Qiao S., Iversen R., Ráki M. Sollid L.M. The adaptive immune response in celiac disease. Semin Immunopathol (2012) 34:523–540.
Jabri B, Kasarda DD, Green PH. Innate and adaptive immunity: the yin and yang of celiac disease. Immunol Rev 2005;206:219–31
Maiuri L, Ciacci C, Auricchio S et al. Interleukin -15 mediates epithelial changes in celiac disease. Gastroenterology 2000; 119: 996–1006.
Malamut G, El Machhour R, Montcuquet N, Martin-Lanneree S, Dusanter-Fourt I, Verkarre V, et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. J Clin Invest 2010;120:2131-43.
Briani C., Samaroo D., Albedini A. Celiac disease: From gluten to autoimmunity. Autoimmunity Reviews 7 (2008) 644–650
Bottazzi, B., A. Doni, C. Garlanda&A.Mantovani. 2010.An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu. Rev. Immunol. 28: 157–183.
Diniz, S.N. et al. 2004. PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages. J. Leukoc. Biol. 75: 649–656.
Rovere, P. et al. 2000. The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen presenting dendritic cells. Blood 96: 4300–4306.
Han, B. et al. 2005. TNF-alpha-induced long pentraxin PTX3 expression in human lung epithelial cells via JNK. J. Immunol. 175: 8303–8311.
Introna, M. et al. 1996. Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites. Blood 87: 1862–1872.
Assandri R, Monari M, Colombo A, et al. Pentraxin 3 Plasma Levels and Disease Activity in Systemic Lupus Erythematosus. Autoimmune Dis 2015;2015:354014
Rovere, P. et al. 2000. The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigenpresenting dendritic cells. Blood 96: 4300–4306.
Lech, M. et al. 2011. Lack of the long pentraxin PTX3 promotes autoimmune lung disease but not glomerulonephritis in murine systemic lupus erythematosus. PloS One 6: e20118.
Luchetti MM, Piccinini G, Mantovani A, Peri G, Matteucci C, Pomponio G, et al. Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol. 2000;119:196–202.
Fazzini F, Peri G, Doni A, Dell’Antonio G, Dal Cin E, Bozzolo E, et al. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum. 2001;44:2841–50.
Dagna L, Salvo F, Tiraboschi M, Bozzolo EP, Franchini S, Doglioni C, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med. 2011;155:425–33.
R. Assandri, M. Monari, A. Colombo, and A. Montanelli,“Pentraxin 3 serum levels in celiac patients: evidences and perspectives,” Recent Patents on Food, Nutrition & Agriculture, vol. 6, no. 2, pp. 82–92, 2015
Bai JC, Fried M, Corazza GR, Schuppan D, Farthing M, Catassi C, Greco L, Cohen H, Ciacci C, Eliakim R, Fasano A, González A, Krabshuis JH, LeMair A; World Gastroenterology Organisation global guidelines on celiac disease J Clin Gastroenterol. 2013 Feb;47(2):121-6.
Hue S, Mention JJ, Monteiro RC et al. A direct role for NKG2D⁄ MICA interaction in villous atrophy during celiac disease. Immunità 2004;21:367–77.
Deban L, Jarva H, Lehtinen MJ, Bottazzi B, Bastone A, et al. (2008) Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation. J Immunol 181: 8433–8440.
Deban L, Russo RC, Sironi M, Moalli F, Scanziani M, et al. (2010) Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol 11:328–334.
Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 2009; 137: 1912-33.
Kooy-Winkelaar Y, van Lummel M, Moustakas AK, Schweizer J, Mearin ML, Mulder CJ, et al. Gluten-specific T cells cross-react between HLA-DQ8 and the HLA-DQ2alpha/DQ8beta transdimer. J Immunol 2011;187:5123-29
Roberto Assandri, Marta Monari, Anna Colombo, Alessandro Montanelli Innate immune system: the no man’s land where discover new biomarkers for gluten-related-disorders Gastroenterol Hepatol Bed Bench 2015;8(2):95-98)
Lv X, Man C, Han L, Wang M, Zhang G, Liu Y, Yang S, Xue Y, Jiang Y Expression of PTX3 gene in Caco-2 cells treated with Lactobacillus acidophilus NCFM. Wei Sheng Wu Xue Bao. 2011 Apr;51(4):554-60
Cooper, B. T. et al. Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology 79, 801–806 (1980).
Francavilla R, Cristofori F, Castellaneta S, Polloni C, Albano V, Dellatte S, Indrio F, Cavallo L, Catassi C. Clinical, Serologic, and Histologic Features of Gluten Sensitivity in ChildrenJ Pediatr. 2013 Nov 16. doi: 10.1016/j.jpeds.2013.10.007.
Volta, U. et al. Serological tests in gluten sensitivity (nonceliac gluten intolerance). J. Clin. Gastroenterol. http://dx.doi.org/ 10.1097/MCG.0b013e3182372541.