α–Chain Disease: A Possible Model for the Pathogenesis of Human Lymphomas

  • Maxime Seligmann
  • Jean-Claude Rambaud
Part of the Comprehensive Immunology book series (COMIMUN, volume 4)

Abstract

α–Chain disease (α–CD) is a proliferative disorder of B lymphoid cells involving primarily the IgA secretory system, in which plasma cells produce a presumably homogeneous population of immunoglobulin (Ig) molecules consisting of incomplete α chains devoid of light (L) chains. Since the first description of this new Ig abnormality (Seligmann et al, 1968) in a young Syrian patient affected with malabsorption and diffuse plasmacytic infiltration of the small intestine (Rambaud et al. 1968), more than 150 cases have been recognized to our knowledge. Thus, α–CD appears to be by far the most frequent of the heavy (H)–chain diseases.

Keywords

Pancreatitis Sarcoma Diarrhea Folate Cyclophosphamide 

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References

  1. Al–Bahrani, Z. R., and Bakir, F., 1971, Primary intestinal lymphoma—Challenging problem in abdominal pain, Ann. R. Coll. Surg. Engl. 49: 103–113.Google Scholar
  2. Bemadou, A., Segond, P., Bilski-Pasquier, G., Mihaesco, E., Preud’homme, J. L., and Bousser, J., 1972, La maladie des chaînes alpha: A propos d’une observation, Nouv. Rev. Fr. Hematol 12: 333.Google Scholar
  3. Bognel, J. C., Rambaud, J. C., Modigliani, R., Matuchansky, C., Bognel, C., Bemier, J. J., Scotto, J., Hautefeuille, P., Mihaesco, E., Hurez, D., Preud’homme, J. L., and Seligmann, M., 1972, Etude clinique, anatomo–pathologique et immunochimique d’un nouveau cas de maladie des chaînes alpha suivi pendant cinq ans, Rev. Eur. Etud. Clin. Biol. 17: 362–374.PubMedGoogle Scholar
  4. Bonomo, L., Dammacco, F., Marano, R., and Bonomo, G. M., 1972, Abdominal lymphoma and alpha chain disease. Am. J. Med. 52: 73.PubMedCrossRefGoogle Scholar
  5. Brandtzaeg, P., and Baklien, K., 1974, Bowel diseases involving local immunoglobulin systems. Acta Pathol. Microbiol. Scand. Sect. A 248: 43–60.Google Scholar
  6. Brouet, J. C., Labaume, S., and Seligmann, M., 1975, Evaluation of T and B lymphocyte membrane markers in human non–Hodgkin malignant lymphomas, Br. J. Cancer 31 (Suppl. 2): 121–127.Google Scholar
  7. Brouet, J. C., Mason, D. Y., Danon, P., Preud’homme, J. L., Seligmann, M., Reyes, P., Navab, P., Galian, A., René, E., and Rambaud, J. C., 1977, Alpha chain disease: Evidence for a common clonal origin of intestinal immunoblastic lymphoma and plasmacytic proliferation. Lancet 1: 861.PubMedCrossRefGoogle Scholar
  8. Buxbaum, J. N., and Preud’homme, J. L., 1972, Alpha and gamma heavy chain diseases in man: Intracellular origin of the aberrant polypeptides, J. Immunol. 109: 1131–1137.PubMedGoogle Scholar
  9. Chadli, A., Hafsia, M., Maamouri, M. T., Haddad, N., and Ayed, K., 1973, Lymphome méditerranéen avec maladie des chaines alpha: Etude anatomopathologique à propos du premier cas tunisien. Arch. Anat. Pathol. 21: 199–210.Google Scholar
  10. Chantar, C., Escartin, P., Plaza, A. G., Corugedo, A. P., Arenas, J. L, Sanz, E., Anaya, A., Bootello, A., and Segovia, J. M., 1974, Diffuse plasma cell infiltration of the small intestine with malabsorp¬tion associated to IgA monoclonal gammapathy. Cancer 34: 1620–1630.PubMedCrossRefGoogle Scholar
  11. Cowan, N. J., Secher, D. S., and Milstein, C., 1974, Intracellular immunoglobulin chain synthesis in non– secreting variants of a mouse myeloma: Detection of inactive light–chain messenger RNA, J. Mol. Biol. 90: 691–701.PubMedCrossRefGoogle Scholar
  12. Dent, C. E., Norris, T. St. M., Smith, R., Sutton, R. A. L., and Temperley, J. M., 1968, Steatorrhoea with striking increase of plasma alkaline–phosphatase of intestinal origin. Lancet 1: 1333–1336.PubMedCrossRefGoogle Scholar
  13. Doe, W. P., 1975, Alpha chain disease: Clinicopathological features and relationship to so–called Mediterranean lymphoma, Br. J. Cancer 31 (Suppl. 2): 350–355.Google Scholar
  14. Doe, W. P., Henry, K., Hobbs, J. R., Avery Jones, E., Dent, C. E., and Booth, C. C., 1972, Pive cases of alphα–chain disease. Gut 13: 947–957.PubMedCrossRefGoogle Scholar
  15. Dorrington, K. J., Mihaesco, E., and Seligmann, M., 1970, The molecular size of three α–chain disease proteins, Biochim. Biophys. Acta 221: 647–649.PubMedGoogle Scholar
  16. Dutz, W., Asvadi, S., Sadri, S., and Kohout, E., 1971, Intestinal lymphoma and sprue: A systematic approach. Gut 12: 804–810.PubMedCrossRefGoogle Scholar
  17. Eidelman, S., Parkins, A., and Rubin, C., 1966, Abdominal lymphoma presenting as malabsorption: A clinicopathologic study of 9 cases in Israel and a review of the literature. Medicine (Baltimore) 45: 111–137.Google Scholar
  18. Paux, J. A., Grain, J. D., Rosen, P. S., and Merler, E., 1973, An alpha heavy chain abnormality in a child with hypogammaglobulinemia, Clin. Immunol. Immunopathol. 1: 282–290.CrossRefGoogle Scholar
  19. Plorin–Christensen, A., Doniach, D., and Newcomb, P. B., 1974, Alpha chain disease with pulmonary manifestations, Br. Med. J. 2: 413–415.CrossRefGoogle Scholar
  20. Prangione, B., and Franklin, E. C., 1973, Heavy chain diseases: Clinical features and molecular significance of the disordered immunoglobulin structure, Semin. Hematol. 10: 53–64.Google Scholar
  21. Prangione, B., and Milstein, C., 1969, Partial deletion in the heavy chain disease protein ZUC, Nature (London) 224: 597–599.CrossRefGoogle Scholar
  22. Franklin, E. C., and Prangione, B., 1975, Structural variants of human and murine immunoglobulins, Contemp. Top. Mol. Immunol. 4: 89–126.PubMedGoogle Scholar
  23. Galian, A., Lecestre, M. J., Scotto, J., Bognel, C., Matuchansky, C., and Rambaud, J. C., 1977, Pathological study of alph-chain disease, with special emphasis on evolution. Cancer 39:2081– 2101.CrossRefGoogle Scholar
  24. Grey, H. M., Abel, C. A., Yount,W. J., and Kunkel, H. G., 1968, A subclass of human yA–globulins (’yA2) which lacks the disulfide bonds linking heavy and light chains, J. Exp. Med. 128: 1223.Google Scholar
  25. Guardia, J., Moragas, A., Pedreira, J. D., Perragut, A., Gomez–Perez, J., Martinez–Vasquez, J. M., and Llorens, V., 1972, Enfermedad de las cadenas pesadas alfa (enfermedad de Seligmann), Rev. Clin. Esp. 127: 923–926.PubMedGoogle Scholar
  26. Henry, K., Bird, R. G., and Doe, W. F., 1974, Intestinal coccidiosis in a patient with alphα–chain disease, Br. Med. J. 1: 542–543.CrossRefGoogle Scholar
  27. Irunberry, J., BenaUegue, A., Illoul, G., Timsit, G., Abbadi, M., Benabdallah, S., Boucekkine, T., Ould– Aoudia, J. P., and Colonna, P., 1970, Trois cas de maladie des chaines alpha observés en Algérie, Nouv. Rev. Fr. Hematol 10: 609–616.Google Scholar
  28. Lewin, K. J., Kahn, L. B., and Novis, B. H., 1976, Primary intestinal lymphoma of “Western” and “Mediterranean” type, alpha chain disease and massive plasma cell infiltration: A comparative study of 34 cases, Cancer 38: 2511–2528.PubMedCrossRefGoogle Scholar
  29. Manousos, O. N., Economidou, J. C., Georgiadou, D. E., Pratsika Ougourloglou, K. G., Hadziyannis, S. J., Merikas, G. E., Henry, K., and Doe, W. F., 1974, Alphα–chain disease with clinical, immunological and histological recovery, Br. Med. J. 2: 409–412.PubMedCrossRefGoogle Scholar
  30. Metrass, M. J., Virella, G., Baptista-Cunha, M. A., and Alfonso, G., 1974, Linfoma intestinal productor de cadenas alfa, Sangre 19: 418–434.PubMedGoogle Scholar
  31. Monges, H., Aubert, L., Chamlian, A., Remade, J. P., Mathieu, B., Cougard, A., and Arroyo, H., 1975, Maladie des chaines alpha à forme intestinale: Présentation d’un cas traité par antibiotherapie avec rémission clinique, histologique et immunologique. Arch. Fr. Mal. Appar. Dig. 64: 223–231.Google Scholar
  32. Montoro–Marin, F., Bermejo, M. R., Monzonis Torres, M. C., and Perez Pena, F., 1974, Aspectos evolutivos y necropsicos de un caso de linfoma mediterraneo con enfermedad de cadenas alfa, Med. Clin. 62: 158–161.Google Scholar
  33. Moroz, C., Amir, J., and De Vries, A., 1971, A hereditary immunoglobulin A abnormality—absence of light–heavy–chain assembly: Study of immunoglobulin synthesis in tonsillar cells, J. Clin. Invest. 50: 2726–2733.PubMedCrossRefGoogle Scholar
  34. Nasr, K., Haghighi, P., Bakhshandeh, K., and Haghshenas, M., 1970, Primary lymphoma of the upper small intestine, Gut 11: 673–678.PubMedCrossRefGoogle Scholar
  35. Natori, S., and Garen, A., 1970, Molecular heterogeneity in the amino–terminal region of alkaline– phosphatase, J. Mol. Biol. 49: 577–588.PubMedCrossRefGoogle Scholar
  36. Novis, B. H., Kahn, L. B., and Bank, S., 1973, Alphα–chain disease in Subsaharan Africa, Am. J. Dig. Dis. 18: 679–688.PubMedCrossRefGoogle Scholar
  37. Pittman, F. E., Tripathy, K., Isobe, T., Bolanos, O. M., Osserman, E. F., Pittman, J. C., and Lotero, H. R., 1975, IgA heavy chain disease: A case detected in the Western hemisphere, Am. J. Med. 58: 424–430.PubMedCrossRefGoogle Scholar
  38. Preud’homme, J. L., and Seligmann, M., 1972, Surface–bound immunoglobulins as a cell marker in human lymphoproliferative diseases. Blood 40: 777–794.PubMedGoogle Scholar
  39. Rambaud, J. C., and Matuchansky, C., 1973, Alphα–chain disease: Pathogenesis and relation to Mediter¬ranean lymphoma, Lancet 1: 1430–1432.PubMedCrossRefGoogle Scholar
  40. Rambaud, J. C., Bognel, C., Prost, A., Bemier, J. J., Le Quintrec, Y., Lambling, A., Danon, F., Hurez, D., and Seligmann, M., 1968, Clinico–pathological study of a patient with “Mediterranean” type of abdominal lymphoma and a new type of IgA abnormality (“alpha chain disease”), Digestion 1:321– 336.PubMedCrossRefGoogle Scholar
  41. Rambaud, J. C., Matuchansky, C., Bognel, J. C., Bognel, C., Bemier, J. J., Scotto, J., Perol, C., Ferrier, J. P., Mihaesco, E., Hurez, D., and Seligmann, M., 1970, Nouveau cas de maladie des chaînes alpha chez un Eurasien. Ann. Méd. Interne 121: 135–148.Google Scholar
  42. Rambaud, J. C., Matuchansky, C., Bognel, C., Galian, A., Le Quintrec, Y., and Bernier, J. J., 1972, La maladie des chaines alpha: Rapport avec le “lymphome méditerranéen”: Diagnostic et orientations, thérapeutique s actuelles, Ann. Gastro–enterol. Hepatol. 8: 481–494.Google Scholar
  43. Rambaud, J. C., Piel, J. L., Galian, A., Ledere, J. P., Danon, F., Girard-Pipeau, F., Modigliani, R., and luoul, G., 1978, Rémission complète clinique, histologique et immunologique d’un cas de maladie des chaines alpha traité par antibiothérapie orale, Gastro–enterol. Clin. Biol. 2: 49–61.Google Scholar
  44. Ramot, B., and Hulu, N., 1975, Primary intestinal lymphoma and its relation to alpha heavy chain disease, Br. J. Cancer 31(SuppL 2j: 343–349.Google Scholar
  45. Ramot, B., and Streifler, C., 1966, Raised serum–alkaline phosphatase, Lancet 2: 587.CrossRefGoogle Scholar
  46. Ramot, B., Shanin, N., and Bubis, J. J., 1965, Malabsorption syndrome in lymphoma of small intestine, Isr. J. Med. Sci. 1: 221–226.PubMedGoogle Scholar
  47. Ramot, B., Levanon, M., Hahn, Y., Lahat, N., and Moroz, C., 1977, The mutual clonal origin of the lymphoplasmocytic and lymphoma cell in alpha–heavy chain disease, Clin. Exp. Immunol 27:440– 445.Google Scholar
  48. Rappaport, H., Ramot, B., Hulu, N., and Park, J. K., 1972, The pathology of so–called Mediterranean abdominal lymphoma with malabsorption, Cancer (Philadelphia) 29: 1502–1511.CrossRefGoogle Scholar
  49. Rogé, J., Druet, P., and Marche, C., 1970, Lymphome méditerranéen avec maladie des chaines alpha:Google Scholar
  50. Triple rémission clinique, anatomique et immunologique, Pathol. Biol. 18:851–858. Savilahti, E., and Brandtzaeg, P., 1973, An atypical case of alphα–chain disease, Scand. J. Immunol. 2:322 (abstract).Google Scholar
  51. Scotto, J., Stralin, H., and Caroli, J., 1970, Ultrastructural study of two cases of α–chain disease. Gut 11: 782–788.PubMedCrossRefGoogle Scholar
  52. Seligmann, M., 1975a, Immunochemical, clinical and pathological features of α–chain disease. Arch. Intern. Med. 135: 78–82.PubMedCrossRefGoogle Scholar
  53. Seligmann, M., 1975b, Alpha chain disease, J. Clin. Pathol. 2S(Suppl. Assoc. Clin. Pathol.):6\12–16.Google Scholar
  54. Seligmann, M., and Rambaud, J. C., 1969, IgA abnormalities in abdominal lymphoma (α–chain disease), Isr. J. Med. Sci. 5: 151–157.PubMedGoogle Scholar
  55. Seligmann, M., Danon, F., Hurez, D., Mihaesco, E., and Preud’homme, J. L., 1968, Alpha–chain disease: A new immunoglobulin abnormality. Science 162: 1396–1397.PubMedCrossRefGoogle Scholar
  56. Seligmann, M., Mihaesco, E., Hurez, D., Mihaesco, C., Preud’homme, J. L., and Rambaud, J. C., 1969, Immunochemical studies in four cases of alpha chain disease, J. Clin. Invest. 48: 2374–2389.PubMedCrossRefGoogle Scholar
  57. Seligmann, M., Mihaesco, E., and Frangione, B., 1971, Studies on alpha chain disease, Ann. N. Y. Acad. Sci. 190: 487–500.PubMedCrossRefGoogle Scholar
  58. Shahid, M. J., Alami, S. Y., Nassar, V. H., Balikian, J. B., and Salem, A. A., 1975, Primary intestinal lymphoma with paraproteinemia. Cancer 35: 848–858.PubMedCrossRefGoogle Scholar
  59. Stoop, J. W., Ballieux, R. E., Hijmans, W., and Zegers, B. J. M., 1971, Alpha chain disease with involvement of the respiratory tract in a Dutch child, Clin. Exp. Immunol. 9: 625–635.PubMedGoogle Scholar
  60. Tangun, Y., Saracbasi, Z., Inceman, S., Danon, F., and Seligmann, M., 1975, IgA myeloma globulin and Bence–Jones proteinuria in a diffuse plasmacytoma of small intestine, Ann. Intern. Med. 83: 673.PubMedGoogle Scholar
  61. Teuliéres, J. P., 1975, La maladie des chaines lourdes alpha, M. D. thesis, Claude Bernard University, Lyon, France.Google Scholar
  62. WHO Meeting Report, 1976, Alphα–chain disease and related small intestinal lymphoma. Arch. Fr. Mai. Appar. Dig. 65: 591–607.Google Scholar
  63. Wolfenstein–Todel, C., Mihaesco, E., and Frangione, B., 1974, “Alpha chain disease” protein Def: Internal deletion of a human immunoglobulin Aj heavy chain, Proc. Natl. Acad. Sci. U.S.A. 71:974–978.Google Scholar
  64. Wolfenstein–Todel, C., Mihaesco, E., and Frangione, B., 1975, Variant of a human immunoglobulin:α– Chain disease protein AIT, Biochem. Biophys. Res. Commun. 65: 47–53.CrossRefGoogle Scholar
  65. Zlotnick, A., and Levy, M., 1971,–Heavy chain disease: A variant of Mediterranean lymphoma. Arch. Intern. Med. 128: 432–436.Google Scholar

Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • Maxime Seligmann
    • 1
    • 2
  • Jean-Claude Rambaud
    • 3
  1. 1.Laboratory of Immunochemistry and Immunopathology (INSERM U 108)Hôpital Saint–LouisParis 10France
  2. 2.Research Institute on Blood DiseasesHôpital Saint–LouisParis 10France
  3. 3.Department of Gastroenterology and Research Unit on Physiopathology of Digestion (INSERM U 54), Hôpital Saint–LazareParis 10France

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