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Novel association of gluten sensitivity with immune-mediated neuromuscular syndrome in a dog

      Abstract

      Gluten-related disorders in humans comprise different entities, including coeliac disease. Patients typically have measurable titers of anti-gliadin IgG or IgA (AGAs) and anti-transglutaminase-2 IgA (TG2). In addition to intestinal symptoms, human patients often show various neurological complications. In dogs, the neurological manifestation is rarely reported. Here we describe the muscle and nerve biopsies of an 11-year-old, male Border Terrier presenting with lower motor neuron signs submitted for histological examination. Examination of the biopsies showed an oligofocal lymphohistiocytic and plasmocytic myositis and a diffuse neuropathy of mixed nodo-paranodal and demyelinating type. Suspecting a neuromuscular form of breed-related gluten hypersensitivity, measurements of AGAs and TG2 antibodies were performed. Both titers ranged above control values. Hence, a gluten-related neuromyopathy was diagnosed. A gluten-free diet was prescribed and a complete disappearance of clinical signs was observed. Gluten-related disorders should be considered as a differential diagnosis in dogs with intestinal and neuromuscular signs.

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      References

        • Elli L.
        • Branchi F.
        • Tomba C.
        • Villalta D.
        • Norsa L.
        • Ferretti F.
        • et al.
        Diagnosis of gluten related disorders: celiac disease, wheat allergy and non-celiac gluten sensitivity.
        World J Gastroenterol. 2015; 21: 7110-7119https://doi.org/10.3748/wjg.v21.i23.7110
        • Burkhardt J.G.
        • Chapa-Rodriguez A.
        • Bahna S.L.
        Gluten sensitivities and the allergist: threshing the grain from the husks.
        Allergy. 2018; 73: 1359-1368https://doi.org/10.1111/all.13354
        • Lindfors K.
        • Ciacci C.
        • Kurppa K.
        • Lundin K.E.A.
        • Makharia G.K.
        • Mearin M.L.
        • et al.
        Coeliac disease.
        Nat Rev Dis Primers. 2019; 5 (3)https://doi.org/10.1038/s41572-018-0054-z
        • Shan L.
        • Molberg O.
        • Parrot I.
        • Hausch F.
        • Filiz F.
        • Gray G.M.
        • et al.
        Structural basis for gluten intolerance in celiac sprue.
        Science. 2002; 297: 2275-2279https://doi.org/10.1126/science.1074129
        • Sollid L.M.
        Coeliac disease: dissecting a complex inflammatory disorder.
        Nat Rev Immunol. 2002; 2: 647-655https://doi.org/10.1038/nri885
        • Hadjivassiliou M.
        • Rao D.G.
        • Grinewald R.A.
        • Aeschlimann D.P.
        • Sarrigiannis P.G.
        • Hoggard N.
        • et al.
        Neurological dysfunction in coeliac disease and non-coeliac gluten sensitivity.
        Am J Gastroenterol. 2016; 111: 561-567https://doi.org/10.1038/ajg.2015.434
        • Lowrie M.
        • Garden O.A.
        • Hadjivassiliou M.
        • Sanders D.S.
        • Powell R.
        • Garosi L.
        Characterization of paroxysmal gluten-sensitive dyskinesia in border terriers using serological markers.
        J Vet Intern Med. 2018; 32: 775-781https://doi.org/10.1111/jvim.15038
        • Lowrie M.
        • Hadjivassiliou M.
        • Sanders D.S.
        • Garden O.A.
        A presumptive case of gluten sensitivity in a border terrier: a multisystem disorder?.
        Vet Rec. 2016; 179: 573https://doi.org/10.1136/vr.103910
        • Gross S.
        • Fischer A.
        • Rosati M.
        • Matiasek L.
        • Corlazzoli D.
        • Cappello R.
        • et al.
        Nodo-paranodopathy, internodopathy and cleftopathy: target-based reclassification of Guillain-Barre-like immune-mediated polyradiculoneuropathies in dogs and cats.
        Neuromuscul Disord. 2016; https://doi.org/10.1016/j.nmd.2016.08.015
        • Hadjivassiliou M.
        • Grunewald R.A.
        • Kandler R.H.
        • Chattopadhyay A.K.
        • Jarratt J.A.
        • Sanders D.S.
        • et al.
        Neuropathy associated with gluten sensitivity.
        J Neurol Neurosurg Psychiatry. 2006; 77: 1262-1266https://doi.org/10.1136/jnnp.2006.093534
        • Spagnoli C.
        • Pisani F.
        • Di Mario F.
        • Leandro G.
        • Gaiani F.
        • De' Angelis G.L.
        • et al.
        Peripheral neuropathy and gastroenterologic disorders: an overview on an underrecognized association.
        Acta Biomed. 2018; 89: 22-32https://doi.org/10.23750/abm.v89i9-S.7956
        • Pengiran Tengah D.S.
        • Wills A.J.
        • Holmes G.K
        Neurological complications of coeliac disease.
        Postgrad Med J. 2002; 78: 393-398https://doi.org/10.1136/pmj.78.921.393
        • Hadjivassiliou M.
        • Sanders D.S.
        • Grunewald R.A.
        • Woodroofe N.
        • Boscolo S.
        • Aeschlimann D.
        Gluten sensitivity: from gut to brain.
        Lancet Neurol. 2010; 9: 318-330https://doi.org/10.1016/S1474-4422(09)70290-X
        • Cong L.
        • Pu C.Q.
        • Shi Q.
        • Wang Q.
        • Lu X.H.
        Complement membrane attack complex is related with immune-mediated necrotizing myopathy.
        Int J Clin Exp Pathol. 2014; 7: 4143-4149
        • Hadjivassiliou M.
        • Chattopadhyay A.K.
        • Grunewald R.A.
        • Jarratt J.A.
        • Kandler R.H.
        • Rao D.G.
        • et al.
        Myopathy associated with gluten sensitivity.
        Muscle Nerve. 2007; 35: 443-450https://doi.org/10.1002/mus.20709
        • Choi Y.C.
        • Park G.T.
        • Kim T.S.
        • Sunwoo I.N.
        • Steinert P.M.
        • Kim S.Y.
        Sporadic inclusion body myositis correlates with increased expression and cross-linking by transglutaminases 1 and 2.
        J Biol Chem. 2000; 275: 8703-8710https://doi.org/10.1074/jbc.275.12.8703
        • Choi Y.C.
        • Kim T.S.
        • Kim S.Y.
        Increase in transglutaminase 2 in idiopathic inflammatory myopathies.
        Eur Neurol. 2004; 51: 10-14https://doi.org/10.1159/000074911
        • Korponay-Szabo I.R.
        • Halttunen T.
        • Szalai Z.
        • Laurila K.
        • Kiraly R.
        • Kovacs J.B.
        • et al.
        In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies.
        Gut. 2004; 53: 641-648https://doi.org/10.1136/gut.2003.024836
        • Lowrie M.
        • Garden O.A.
        • Hadjivassiliou M.
        • Harvey R.J.
        • Sanders D.S.
        • Powell R.
        • et al.
        The clinical and serological effect of a gluten-free diet in border terriers with epileptoid cramping syndrome.
        J Vet Intern Med. 2015; 29: 1564-1568https://doi.org/10.1111/jvim.13643
        • Lowrie M.
        • Garosi L.
        Classification of involuntary movements in dogs: paroxysmal dyskinesias.
        Vet J. 2017; 220: 65-71https://doi.org/10.1016/j.tvjl.2016.12.017
        • Bago Rozankovic P.
        • Rozankovic M.
        • Romic Z.C.
        • Basic S.
        Paroxismal non-kinesigenic dyskinesia and hemidystonia associated with silent celiac disease.
        Clin Neurol Neurosurg. 2020; 188105586https://doi.org/10.1016/j.clineuro.2019.105586
        • Singh P.
        • Arora S.
        • Lal S.
        • Strand T.A.
        • Makharia G.K.
        Risk of celiac disease in the first- and second-degree relatives of patients with celiac disease: a systematic review and meta-analysis.
        Am J Gastroenterol. 2015; 110: 1539-1548https://doi.org/10.1038/ajg.2015.296
        • Garden O.A.
        • Pidduck H.
        • Lakhani K.H.
        • Walker D.
        • Wood J.L.
        • Batt R.M.
        Inheritance of gluten-sensitive enteropathy in Irish Setters.
        Am J Vet Res. 2000; 61: 462-468https://doi.org/10.2460/ajvr.2000.61.462
        • Hadjivassiliou M.
        • Croall I.D.
        • Zis P.
        • Sarrigiannis P.G.
        • Sanders D.S.
        • Aeschlimann P.
        • et al.
        Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6.
        Clin Gastroenterol Hepatol. 2019; 17 (e2): 2678-2686https://doi.org/10.1016/j.cgh.2019.03.014
        • Lorand L.
        • Iismaa S.E.
        Transglutaminase diseases: from biochemistry to the bedside.
        FASEB J. 2019; 33: 3-12https://doi.org/10.1096/fj.201801544R