Horm Metab Res 2004; 36(2): 97-100
DOI: 10.1055/s-2004-814218
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Autoimmune Diabetes mellitus, Hodgkin’s Disease and Graves’ Ophthalmopathy in a Patient with 8.1 Ancestral Haplotype

E.  De Carlo1 , G.  Tamagno1 , C.  Martini1 , P.  Maffei1 , D.  Rubello2 , M.  Luca3 , N.  Sicolo1
  • 1Department of Medical and Surgical Sciences, Clinica Medica III, University of Padova, Italy
  • 2Second Nuclear Medicine Service, Padova Hospital, Italy
  • 3Immunohematology and Transfusion Service, Padova Hospital, Italy
Further Information

Publication History

Received 6 May 2003

Accepted after revision 28 August 2003

Publication Date:
05 March 2004 (online)

Abstract

In this report, we describe the case of a 43-year-old woman affected by type 1 diabetes mellitus diagnosed 8 years before, who developed Graves’ disease 2 years after chemotherapy and mantle radiotherapy treatment for Hodgkin’s disease. Bilateral Graves’ ophthalmopathy appeared four months before our observations. Intravenous methyl-prednisolone therapy was started, but was interrupted due to severe metabolic failure. Autoantibodies (anti-islet cells, anti-thyroid, thyroid-stimulating, non-organ-specific) were positive. Since the clinical picture suggested a genetic immunological ground predisposing to autoimmunity, we evaluated her HLA haplotype. Genomic typing of the patient permitted identification of the 8.1 ancestral haplotype, a Caucasoid haplotype unique in its association with many immunopathological diseases. Moreover, we also observed a haplotype unusual in Caucasians, trans DRB1*1101, DQA1*0103, DQB1*0603. To our knowledge, HLA-related genetic risk of developing thyroid autoimmunity after neck irradiation has never been studied. Although we cannot confirm a direct association between the 8.1 ancestral haplotype or DRB1*1101, DQA1*0103, DQB1*0603 and the diseases described, we suggest considering immunological parameters and HLA typing in candidate patients for mantle radiation therapy for Hodgkin’s disease or other tumors. HLA haplotype determination could be useful in identifying the patients at raised risk of developing autoimmune diseases after irradiation, thus permitting a more appropriate follow-up schedule.

References

  • 1 Ringel M D, Taylor T, Barsouk A, Wall J R, Freter C E, Howard R S, Diehl L, Burman K D. Hodgkin’s disease treated with neck radiation is associated with increased antibody-dependent cellular cytotoxicity against human extraocular muscle cells.  Thyroid. 1997;  7 425-432
  • 2 Urba W J, Longo D L. Hodgkin’s disease.  The New England Journal of Medicine. 1992;  326 678-687
  • 3 Maugendre D, Vérité F, Guilhem I, Genetet B, Allannic H, Delamaire M. Anti-pancreatic autoimmunity and Graves’ disease: study of a cohort of 600 Caucasian patients.  European Journal of Endocrinology. 1997;  137 503-510
  • 4 Mann D L, Murray C. HLA alloantigens: disease association and biologic significance.  Seminars in Hematology. 1979;  16 293-306
  • 5 Kockum I, Lernmark A, Dahlquist G, Falorni A, Hagopian W A, Landin-Olsson M, Li L C, Luthman H, Palmer J P, Sanjeevi C B, Sundkvist G, Ostman I J. Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The Diabetes incidence in Sweden Study (DISS) Group.  Hormone and Metabolic Research. 1996;  28 344-347
  • 6 Staratschek-Jox A, Shugart Y Y, Strom S S, Nagler A, Taylor G M. Genetic susceptibility to Hodgkin lymphoma and to secondary cancer: workshop report.  Annals of Oncology. 2002;  13 30-33
  • 7 Mourits M P, Prummel M F, Wiersinga W M, Koornnef L. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy.  Clinical Endocrinology (Oxf). 1997;  47 9-14
  • 8 Price P, Witt C, Allcock R, Sayer D, Garlepp M, Choy Kok C, French M, Mallal S, Christiansen F. The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases.  Immunological Reviews. 1999;  167 257-274
  • 9 Ghandour C, La Prise P Y, Hespel J P. Hodgkin Disease and Hyperthyroidism.  Acta Haematologica. 1985;  74 137-143
  • 10 Hancock S L, Cox R S, McDougall I R. Thyroid diseases after treatment of Hodgkin disease.  The New England Journal of Medicine. 1991;  325 599-605
  • 11 Loeffler J S, Tarbell N J, Garber J R, Mauch P. The development of Graves disease following radiation therapy in Hodgkin’s disease.  International Journal of Radiation Oncology, Biology, Physics. 1988;  14 175-178
  • 12 Wasnich R D, Grumet F C, Payne R O, Kriss J P. Graves’ ophthalmopathy following external neck irradiation of non thyroidal neoplastic disease.  Journal of Clinical Endocrinology and Metabolism. 1973;  37 703-713
  • 13 Pasqualini T, Iorcansky , Gruneiro L, Diez B, Pavlovsky S, Sackmann-Muriel F, Rivarola M A. Thyroid disfunction in Hodgkin’s disease.  Cancer. 1989;  63 335-339
  • 14 Bahn R S, Heufelder A E. Pathogenesis of Graves’ ophthalmopathy.  New England Journal of Medicine. 1993;  329 1468-1475
  • 15 Mengitsu M, Lukes Y G, Nagy E V, Burch H B, Carr F E, Lahiri S, Burman K D. TSH receptor gene expression in retroocular fibroblasts.  Journal of Endocrinological Investigation. 1994;  17 437-441
  • 16 McGregor A M, McLachlan S M, Smith B R. Effect of irradiation on thyroid-autoantibody production.  Lancet. 1979;  1;2 (8140) 442-443
  • 17 Dobbs H J. Thyroid damage-after treatment for Hodgkin’s disease.  Clinical Oncology. 1983;  9 51-56
  • 18 Lio D, Candore G, Colombo A, Colonna Romano G, Gervasi F, Marino V, Scola L, Caruso C. A genetically determined high setting of TNF-α influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity.  Human Immunology. 2001;  62 705-713
  • 19 Mysliwiec J, Kretowski A, Topolska J, Siewko K, Jakubczyk D, Szelachowska M, Mikita A, Kinalska I. Serum Th1 and Th2 profile cytokine level changes in patients with Graves’ ophthalmopathy treated with corticosteroids.  Hormone and Metabolic Research. 2001;  33 739-743
  • 20 Hiromatsu Y, Kaku H, Miyake I, Murayama S, Soejima E. Role of cytokines in the pathogenesis of thyroid-associated ophthalmopathy.  Thyroid. 2002;  12 217-221
  • 21 Wallaschofski H, Meyer A, Tuschy U, Lohmann T. HLA-DQA1*0301-associated susceptibility for Autoimmune Polyglandular Syndrome Type II and III.  Hormone and Metabolic Research. 2003;  35 120-124
  • 22 Kalmann R, Mourits M P. Diabetes mellitus: a risk factor in patients with Graves’ orbitopathy.  British Journal of Ophthalmology. 1999;  83 (4) 463-465
  • 23 O’Connor T M, Cronin C C, Loane J F, O’Mearat N M, Firth R G, Shanahan F, O’Halloran D J. Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.  Diabetic Medicine. 1999;  16 614-617

E. De Carlo

Clinica Medica III

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