Skip to main content
PMC home page
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 1969;41(6):793–804.

Immunological aspects of leprosy with special reference to autoimmune diseases

O Wager
PMCID: PMC2427576  PMID: 5309531

Abstract

Leprosy, particularly lepromatous leprosy, is associated with a multitude of (auto) immune aberrations, and its clinical features also have much in common with the collagen diseases. Immunopathological studies of the 2 groups of diseases may thus elucidate the basic mechanisms of both.

The reported evidence for a genetically determined hyporeactivity of cell-mediated (CM) immunity in lepromatous subjects is reviewed; most, but not all, of the findings fit such a hypothesis well. The possibility remains that the observed hyporeactivities may be secondary to direct effects of Mycobacterium leprae. Evidence for a general hyperreactivity of the antibody-mediated (AM) immunity in lepromatous leprosy is then reviewed and considered to be fragmentary.

The concept and general criteria of autoimmunity are discussed briefly and the high incidence in lepromatous leprosy of various (auto)immune aberrations, resembling those in systemic lupus erythematosus (SLE) and in rheumatoid arthritis is reviewed. Although autoantibodies are not likely to be directly deleterious to the host, immune complexes containing autoantibodies may be pathogenic.

Mixed cryoimmunoglobulins, consisting of 2 (IgG—IgM or IgG—IgA) or 3 immunoglobulins, and occasionally also containing measurable amounts of complement components, have recently been encountered in SLE and its variants and also in a number of microbial diseases with autoimmune features (syphilis, streptococcal nephritis and endocarditis, mononucleosis, Mycoplasma pneumoniae pneumonia). They may represent circulating immune complexes, analogous to the IgM (IgA) rheumatoid factors in combination with their IgG reactants. In leprosy also, the existence of pathogenic immune complexes is indirectly suggested by mixed cryoglobulinemia and further by a number of other features reviewed in this article.

Full text

PDF
794

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABRUZZO J. L., CHRISTIAN C. L. The induction of a rheumatoid factor-like substance in rabbits. J Exp Med. 1961 Nov 1;114:791–806. doi: 10.1084/jem.114.5.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. AHO K., KONTTINEN A., RAJASALMI M., WAGER O. Transient appearance of the rheumatoid factor in connection with prophylactic vaccinations. Acta Pathol Microbiol Scand. 1962;56:478–479. doi: 10.1111/j.1699-0463.1962.tb04201.x. [DOI] [PubMed] [Google Scholar]
  3. AHO K., WAGER O. Production of anti-antibodies in rabbits. Ann Med Exp Biol Fenn. 1961;39:79–87. [PubMed] [Google Scholar]
  4. BONOMO L., DAMMACCO F., PINTO L., BARBIERI G. THYROGLOBULIN ANTIBODIES IN LEPROSY. Lancet. 1963 Oct 19;2(7312):807–809. doi: 10.1016/s0140-6736(63)90501-4. [DOI] [PubMed] [Google Scholar]
  5. BUCK A. A., HASENCLEVER H. F. The influence of leprosy on delayed-type skin reactions and serum agglutination titers to Candida albicans. A comparative study of patients with lepromatous and tuberculoid leprosy and controls in Ethiopia. Am J Hyg. 1963 May;77:305–316. doi: 10.1093/oxfordjournals.aje.a120321. [DOI] [PubMed] [Google Scholar]
  6. Bonomo L., Dammacco F., Tursi A., Barbieri G. Lupoid features in a case of leprosy. Int J Lepr Other Mycobact Dis. 1967 Jan-Mar;35(1):65–71. [PubMed] [Google Scholar]
  7. Burnet F. M. Measles as an index of immunological function. Lancet. 1968 Sep 14;2(7568):610–613. doi: 10.1016/s0140-6736(68)90701-0. [DOI] [PubMed] [Google Scholar]
  8. Catsoulis E. A., Franklin E. C., Rothschild M. A. Cryoglobulinaemia in rabbits hyperimmunized with a polyvalent pneumococcal vaccine. Immunology. 1965 Oct;9(4):327–331. [PMC free article] [PubMed] [Google Scholar]
  9. Cooper M. D., Gabrielsen A. E., Good R. A. Role of the thymus and other central lymphoid tissues in immunological disease. Annu Rev Med. 1967;18:113–138. doi: 10.1146/annurev.me.18.020167.000553. [DOI] [PubMed] [Google Scholar]
  10. Dierks R. E., Shepard C. C. Effect of phytohemagglutinin and various mycobacterial antigens on lymphocyte cultures from leprosy patients. Proc Soc Exp Biol Med. 1968 Feb;127(2):391–395. doi: 10.3181/00379727-127-32698. [DOI] [PubMed] [Google Scholar]
  11. Dixon F. J. Antigen-antibody complexes and autoimmunity. Ann N Y Acad Sci. 1965 Jun 30;124(1):162–166. doi: 10.1111/j.1749-6632.1965.tb18954.x. [DOI] [PubMed] [Google Scholar]
  12. GUINTO R. S., MABALAY M. C. A note on the tuberculin reaction in leprosy. Int J Lepr. 1962 Jul-Sep;30:278–283. [PubMed] [Google Scholar]
  13. Hanauer L. B., Christian C. L. Studies of cryoproteins in systemic lupus erythematosus. J Clin Invest. 1967 Mar;46(3):400–408. doi: 10.1172/JCI105541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hart P. D., Rees R. J. Lepromin and Kveim antigen reactivity in man, and their relation to tuberculin reactivity. Br Med Bull. 1967 Jan;23(1):80–85. doi: 10.1093/oxfordjournals.bmb.a070522. [DOI] [PubMed] [Google Scholar]
  15. Houba V., Adam M., Malecek J., Tesárek B. Delayed hypersensitivity and antibody response in rheumatoid arthritis. Experientia. 1964 Sep 15;20(9):522–523. doi: 10.1007/BF02154091. [DOI] [PubMed] [Google Scholar]
  16. Jansson E., Wager O. Mycoplasma in collagen diseases and blood dyscrasia. Ann N Y Acad Sci. 1967 Jul 28;143(1):535–543. doi: 10.1111/j.1749-6632.1967.tb27700.x. [DOI] [PubMed] [Google Scholar]
  17. LOSPALLUTO J., DORWARD B., MILLER W., Jr, ZIFF M. Cryoglobulinemia based on interaction between a gamma macroglobulin and 7S gamma globulin. Am J Med. 1962 Jan;32:142–147. doi: 10.1016/0002-9343(62)90191-2. [DOI] [PubMed] [Google Scholar]
  18. Matthews L. J., Trautman J. R. Clinical and serological profiles in leprosy. Lancet. 1965 Nov 6;2(7419):915–917. doi: 10.1016/s0140-6736(65)92899-0. [DOI] [PubMed] [Google Scholar]
  19. Meltzer M., Franklin E. C. Cryoglobulinemia--a study of twenty-nine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med. 1966 Jun;40(6):828–836. doi: 10.1016/0002-9343(66)90199-9. [DOI] [PubMed] [Google Scholar]
  20. Michalany J. Malignant tumors of the skin among leprosy patients. Int J Lepr Other Mycobact Dis. 1966 Jul-Sep;34(3):274–286. [PubMed] [Google Scholar]
  21. Myllylä G., Vaheri A., Vesikari T., Penttinen K. Interaction between human blood platelets, viruses and antibodies. IV. Post-Rubella thrombocytopenic purpura and platelet aggregation by Rubella antigen-antibody interaction. Clin Exp Immunol. 1969 Mar;4(3):323–332. [PMC free article] [PubMed] [Google Scholar]
  22. Norlin M., Navalkar R. G., Ouchterlony O., Lind A. Characterization of leprosy sera with various mycobacterial antigens using double diffusion-in-gel analysis. 3. Acta Pathol Microbiol Scand. 1966;67(4):555–562. doi: 10.1111/apm.1966.67.4.555. [DOI] [PubMed] [Google Scholar]
  23. OLIVEIRADEALMEIDA J., BRANDAO H., GARCIADELIMA E. ENHANCED SEROLOGIC RESPONSE OF LEPROMATOUS PATIENTS TO ANTITYPHOID VACCINATION. Int J Lepr. 1964 Jul-Sep;32:292–296. [PubMed] [Google Scholar]
  24. OORT J., TURK J. L. A HISTOLOGICAL AND AUTORADIOGRAPHIC STUDY OF LYMPH NODES DURING THE DEVELOPMENT OF CONTACT SENSITIVITY IN THE GUINEA-PIG. Br J Exp Pathol. 1965 Apr;46:147–154. [PMC free article] [PubMed] [Google Scholar]
  25. PEETOOM F., LOGHEM-LANGEREIS E. IGM-IGG (BETA-2M-7S-GAMMA) CRYOGLOBULINAEMIA AN AUTO-IMMUNE PHENOMEMON. Vox Sang. 1965 May-Jun;10:281–292. doi: 10.1111/j.1423-0410.1965.tb01391.x. [DOI] [PubMed] [Google Scholar]
  26. Parrott D. V., De Sousa M. A., East J. Thymus-dependent areas in the lymphoid organs of neonatally thymectomized mice. J Exp Med. 1966 Jan 1;123(1):191–204. doi: 10.1084/jem.123.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Penttinen K., Myllylä G. Interaction in human blood platelets, viruses and antibodies. I. Platelet aggregation test with microequipment. Ann Med Exp Biol Fenn. 1968;46(2):188–192. [PubMed] [Google Scholar]
  28. Rees R. J., Chatterjee K. R., Pepys J., Tee R. D. Some immunologic aspects of leprosy. Am Rev Respir Dis. 1965 Dec;92(6):139–149. doi: 10.1164/arrd.1965.92.6P2.139. [DOI] [PubMed] [Google Scholar]
  29. SALVIN S. B. Immunologic aspects of the mycoses. Prog Allergy. 1963;7:213–331. doi: 10.1159/000391342. [DOI] [PubMed] [Google Scholar]
  30. Turk J. L., Waters M. F. Immunological basis for depression of cellular immunity and the delayed allergic response in patients with lepromatous leprosy. Lancet. 1968 Aug 24;2(7565):436–438. doi: 10.1016/s0140-6736(68)90472-8. [DOI] [PubMed] [Google Scholar]
  31. Turk J. L., Willoughby D. A. Central and peripheral effects of anti-lymphocyte sera. Lancet. 1967 Feb 4;1(7484):249–251. doi: 10.1016/s0140-6736(67)91307-4. [DOI] [PubMed] [Google Scholar]
  32. Unanue E. R., Dixon F. J. Experimental glomerulonephritis: immunological events and pathogenetic mechanisms. Adv Immunol. 1967;6:1–90. doi: 10.1016/s0065-2776(08)60521-0. [DOI] [PubMed] [Google Scholar]
  33. VAUGHAN J. H. Serum responses in rheumatoid arthritis. Am J Med. 1959 Apr;26(4):596–613. doi: 10.1016/0002-9343(59)90281-5. [DOI] [PubMed] [Google Scholar]
  34. Wager O., Mustakallio K. K., Räsänen J. A. Mixed IgA-IgG cryoglobulinemia. Immunological studies and case reports of three patients. Am J Med. 1968 Feb;44(2):179–187. doi: 10.1016/0002-9343(68)90149-6. [DOI] [PubMed] [Google Scholar]
  35. Wager O., Räsänen J. A., Hagman A., Klemola E. Mixed cryoimmunoglobulinaemia in infectious mononucleois and Cytomegalovirus mononucleosis. Int Arch Allergy Appl Immunol. 1968;34(4):345–361. doi: 10.1159/000230129. [DOI] [PubMed] [Google Scholar]
  36. Wager O., Räsänen J. A., Lassus A., Mustakallio K. K. Mixed cryoimmunoglobulins. Acta Pathol Microbiol Scand. 1967;69(4):610–611. doi: 10.1111/j.1699-0463.1967.tb03769.x. [DOI] [PubMed] [Google Scholar]
  37. Waldorf D. S., Sheagren J. N., Trautman J. R., Block J. B. Impaired delayed hypersensitivity in patients with lepromatous leprosy. Lancet. 1966 Oct 8;2(7467):773–776. doi: 10.1016/s0140-6736(66)90366-7. [DOI] [PubMed] [Google Scholar]
  38. Wasastjerna C., Kalliola H., Räsänen J. A., Wager O. IgG cryoglobulinaemia Case report and immunological studies of a patient with recurrent ulcerative stomatitis and high content of cold precipitable immunoglobulin in serum. Scand J Haematol. 1967 Dec;4(6):473–484. [PubMed] [Google Scholar]
  39. de Azevedo M. P., de Melo P. H. A comparative study of the complementary activity of serum in the polar forms of leprosy and in the leprosy reaction. Int J Lepr Other Mycobact Dis. 1966 Jan-Mar;34(1):34–38. [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES