"N-Factor/Anergic Margin" or Resistance/Susceptibility to hanseniasis. 111. The general acceptance of the theory under other names, a few pending questions and the related researches ahead
DOI:
https://doi.org/10.47878/hi.1978.v3.36078Keywords:
Hanseniasis, Genetics, Immunology, Mitsuda test, N-Factor, Anergic MarginAbstract
In this third and final article of a series, the general acceptance of the "N-Factor/Anergic Margin" theory, under other names, is reported. "Constitutional capacity to react", "genetical aptitude" and "potential immunity" stand among the numerous synonyms for the old (1937) "natural" N-Factor; "lepromatous macrophage defect", "specific defect of cell-mediated immunity" are pathogenetical explanations for the "Anergic Margin" (AM). However, "depression" and "impairment" of immunity are not included among the synonyms for the AM, as, according to the theory, energy precedes and conditions VirchowIan hanseniasis, is not caused by it. Secondary unspecific depression of cell-mediated immunity possibly exists in moderately advanced cases of Virchowian hanuPniagig, but has no relationship with the primary genetical incapacity to react to Mycobacterium hansenii, which characterizes the AM of the general population. Studies with homozygotic twins and HL-A antigens support the theory of a genetical conditioning of types of hanseniasis. Many works on the immunogenetics of the disease were inconclusive, partly due to the fact that Mitsuda-negative persons were wrongly considered as a homogeneous group, not as a heterogeneous group ranging from total energy (the AM) to the highest grades of Mitsuda responsiveness (only needing the stimulation by mycobacteria, especially Hansen's and Koch's). "N-Factor" bearers (reactors) and AM members (non-reactors) exist in the whole world, endemic and non-endemic, and constitute an ample field for research. Further investigations to clarify some of the pending questions are suggested.
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References
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13. FLIESS, E.L.; BALIFIA, L.M.; BACHMANN, A.E.; CARDAMA, J.E. GATTI, J.C. Alteraciones de la desdiferenciación linfoblástica en pacientes de lepra lepromatosa y sus consanguíneos sans lepromino-negativos. Leprologia, 17(2) :83-90, 1972.
14. GODAL. T. The nature of the immunological defect in lepromatous leprosy. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen, 1973. Transactions spud Int. J. Lepr., 41(4) :538, 1973.
15. GODAL, T. Growing points in leprosy research (3). Immunological detection of sub-clinical infection in leprosy. Lepr. Rev., 45(1) :22-30, 1974.
16. GODAL, T.; LOFGREN, M.; NEGASSI, K. Immune response to M. leprac of healthy leprosy contacts. Int. J. Lepr., 40(3).243-250, 1972.
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19. LEVINSON, A.I.; LISAK, R.P.; ZWEIMAN, B. Immunologic aspects of leprosy. Int. J. Dermatol., 16:103-112, 1977.
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21. MARTINEZ-DOMINGUEZ, V. Estudio epidemiológico y clinico de la endemia de lepra en la Guinea Espanola. In: CONGRESO INTERNACIONAL DE LEPROLOGIA, 6.°, Madrid, 1953. Memoria. Madrid, 1954. p. 1104-1204.
22. MEHRA, N.K.; DASGUPTA, A.; VAIDYA, M.C. An evaluation of the immune state in leprosy. Leprosy India, 48(3) :231-237, 1976.
23. MYRVANG, B. Immune responses to Mycobacterium lepras in man. J. Oslo City Hosp., 25:3-24, 1975.
24. PEREIRA, A. C. Doses repetidas de BCG oral .na imunização contra a lepra. In: CONGRESSO MUNDIAL DA SOCIEDADE INTERNACIONAL DE DERMATOLOGIA TROPICAL, 3.°, São Paulo, 1974. Temas livres. item 187.
25. PRREZ-PEREZ, B. Profilaxia antileprosa en paises de pequena endemia. El BCG en la profilaxis de la lepra. Rev. Leprol. Fontilles, 0(6):559-629, 1974.
26. PIMENTA, W.P. Contribution to the study of the nonspecificity of the tuberculin at high concentrations (Palmer and co-workers hypothesis) in patients with lepromatous leprosy and patients affected by other diseases. Ribeirão Preto, 1963. [Thesis - Faculty of Medicine, Ribeirão Preto University] Acta Leprol., (37) :5-66, 1969.
27. REA, T.H.; GOTTLIEB, B.; LEVAN, N. E. Apparently normal skin in lepromatous leprosy. Arch. Dermatol., 111(12) :1571-1574, 1975.
28. REA, T.H.; QUISMORIO, F.P.; HARDING, B.; NIES, K.M.; DI SAIA, P.J.; LEVAN, N.E. FRIOU, G.J. Immunologic responses in patients with lepromatous leprosy. Arch. Dermatol., 112(6) :791-800, 1976.
29. ROTBERG, A. Estudos sobre as reações tuberculínicas na lepra. Rev. Bras. Leprol., 6 (3) :245-272, 1938.
30. ROTBERG, A. Fator: "N" de resistência à lepra e relações com a reatividade lepromínica e tuberculinica. Valor duvidoso do BCG na imunização antileprosa. ("N-Factor" of resistance to leprosy and its relationship with reactivity to lepromin and tuberculin. Doubtful value of BCG in anti-leprous immunization). Rev. Bras. Leprol., 25(2) :25-106, 1957.
31. ROTBERG, A. The influence of allergic factors in the pathogenesis of leprosy. In: PACIFIC SCIENCE CONGRESS, 6th, Berkeley, California, 1939. Proceedings. v.5. p. 977-982.
32. ROTBERG, A. Modern trends in the study of the epidemiology of leprosy. In: PACIFIC SCIENCE CONGRESS, 6th, Berkeley, California, 1939. Proceedings. v.5, p 939-945.
33. ROTBERG, A. "N-Factor/Anergic Margin" or resistance/susceptibility to hanseniasis. I. The foundations of the theory. Hansen. hit., 2(2):115-124, 1977.
34. ROTBERG, A. "N-Factor/Anergic Margin" or resistance/susceptibility to hanseniasis. H. The general acceptance of the theory. Hansen. Int., 2(2) :125-134, 1977.
35. ROTBERG, A. Some aspects of immunity in leprosy and their importance in epidemiology,;, pathogenesis and classification of forms of the disease. Based on 1529 lepromin-tested cases. Rev. Bras. Leprol., 5(n.° esp.) :45-97, 1937.
36. ROTBERG, A.; BECHELLI, L.M.; KEIL, H. The Mitsuda reaction in a non-leprous area. Int. J. Lepr., 18(2) :209-220, 1950.
37. SAHA, K. & MITTAL, M.M. A study of cell mediated immunity in leprosy: changing trends in the immunological spectrum of the disease. Clin. Exp. Immunol., 8(6):901-909, 1971.
38. SAINT-ANDRE, P.; BUENO A.M. Study of tuberculin-type delayed allergy to living bodies. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen. 1973. Transactions apud Int. J. Lepr., 41(4) :562, 1973.
39. SOUZA CAMPOS, N.S.; ROTBERG, A.; BECHELLI, L.M.; GINEFRA, M. Estudos sobre a viragem da lepromino-reação pelo BCG. (III) Resultados da lepromino-reação em coletividade de filhos de hansenianos e tentativas de viragem dos lepromino-negativos, duvidosos ou francamente positivos mediante esquemas variados de
administração da BCG. In: CONGRESSO INTERNACIONAL DE LEPROLOGIA, 8.° Rio de Janeiro, 1963. Anais. Rio de Janeiro, Serviço Nacional de Lepra, 1963. v.3. p. 310-322.
40. TURK, J.L.; & WATERS, M.F.R. Immunological significance of changes in lymph nodes across the leprosy spectrum. Clin. Exp. Imunol., 8:363-376, 1971.
41. WATERS, M.F.R. Significance of the lepromin test in tuberculin-negative volunteers permanently resident in a leprosy-free area. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen, 1973. Transactions apud Int. J. Lepr., 41 (4) :563, 1975.
2. AZULAY, R.D. & CONVIT, J. The Mitsuda test in non-leprous persons in a non-endemic country. Int. J. Lepr., 15(3) :264-266, 1947.
3. BALIÑA(A, L.M.; FLIESS, E.L.; BACHMANN, A.E.; CARDAMA, J. E.; GATTI, J.C. Similar alterations of lymphoblastic dedifferentiation in lepromatous patients and their healthy lepromin-negative offspring. Int. J. Lepr., 41(1) :7-13, 1973.
4. BECHELLI, L.M. A review of present literature on the immuno-allergic correlation between tuberculosis and leprosy. Acta Leprol., (42/43):63-118, 1971.
5. BECHELLI, L.M.; RATH DE SOUZA, P.; QUAGLIATO. R. Correlação entre os resultados da leitura clínica e do exame histopatológico da reação de Mitsuda. Rev. Bras. Leprol., 25(1) :21-58, 1957.
6. BEIGUELMAN, B. Genética na hanseniase. Hansen. Int. 3:179-193, 1978.
7. BULLOCK, W.E. Studies of immune mechanisms in leprosy. I. Depression of delayed allergic response to skin test antigens. New Engl. Med. J., 278(6) :298-304, 1968.
8. CHAKRAVARTI, M.R. & VOGEL, F. A twin study on leprosy. Topics Hum. Genet., 1:1-123, 1973 apud MEHRA, N.K.; DASGUPTA, A.; VAIDYA. M.C. An evaluation of the immune state in leprosy. Lepr. India, 48(3) :231-237, 1976.
9. CONGRESSO INTERNACIONAL DE LEPROLOGIA, 8.°, Rio de Janeiro, 1963. Relatório do grupo de trabalho sobre bacteriologia e imunologia. II imunologia. In: Relatórios finais das comissões técnicas aprovados em sessão plenária de 20 de setembro de 1968. Rio de Janeiro, 1963. p. 61-78.
10. CONVIT, J. & PINARDI, M.E. Estudio comparativo entre la lepra lepromatosa y la leishmaniasis tegumentaria difusa como enfermedades por defecto inmunológico del huesped. Acta Cient. Venez., 21(supl.l) :58, 1970 apud Dermatol. Ibero Lat. Amer. 12(3) :308-309, 1970.
11. DEL FAVERO, W. O censo intensivo em Candeias. Bol. Serv. Nac. Lepra, 6:87-235, 1948.
12. DOULL, J.A.; GUINTO, R.S.; MABALAY, M.C. Effect of BCG vaccination, lepromin testing and natural causes in inducing reactivity to lepromin and to tuberculin. Int. J. Lepr., 25:(1):13-37, 1957.
13. FLIESS, E.L.; BALIFIA, L.M.; BACHMANN, A.E.; CARDAMA, J.E. GATTI, J.C. Alteraciones de la desdiferenciación linfoblástica en pacientes de lepra lepromatosa y sus consanguíneos sans lepromino-negativos. Leprologia, 17(2) :83-90, 1972.
14. GODAL. T. The nature of the immunological defect in lepromatous leprosy. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen, 1973. Transactions spud Int. J. Lepr., 41(4) :538, 1973.
15. GODAL, T. Growing points in leprosy research (3). Immunological detection of sub-clinical infection in leprosy. Lepr. Rev., 45(1) :22-30, 1974.
16. GODAL, T.; LOFGREN, M.; NEGASSI, K. Immune response to M. leprac of healthy leprosy contacts. Int. J. Lepr., 40(3).243-250, 1972.
17. HAYASHI, F. Mitsuda's skin reaction in leprosy. Int. J. Lepr., 1(1) :31-38, 1933.
18. KREISLER, M.; ARNAIZ, A.; PEREZ, B.; CRUZ, E.F.; BOOTELLO, A. HL-A antigens in leprosy.' Tissue Antigens, 4:197-201, 1974.
19. LEVINSON, A.I.; LISAK, R.P.; ZWEIMAN, B. Immunologic aspects of leprosy. Int. J. Dermatol., 16:103-112, 1977.
20. LOUVET, M.; SAINT ANDRE, P. BERNARD, L. Aspect épidemiologique actuei de la lèpre en Afrique deI l'Oueat. Acta Leprol. (66/67) :33-36, 1977.
21. MARTINEZ-DOMINGUEZ, V. Estudio epidemiológico y clinico de la endemia de lepra en la Guinea Espanola. In: CONGRESO INTERNACIONAL DE LEPROLOGIA, 6.°, Madrid, 1953. Memoria. Madrid, 1954. p. 1104-1204.
22. MEHRA, N.K.; DASGUPTA, A.; VAIDYA, M.C. An evaluation of the immune state in leprosy. Leprosy India, 48(3) :231-237, 1976.
23. MYRVANG, B. Immune responses to Mycobacterium lepras in man. J. Oslo City Hosp., 25:3-24, 1975.
24. PEREIRA, A. C. Doses repetidas de BCG oral .na imunização contra a lepra. In: CONGRESSO MUNDIAL DA SOCIEDADE INTERNACIONAL DE DERMATOLOGIA TROPICAL, 3.°, São Paulo, 1974. Temas livres. item 187.
25. PRREZ-PEREZ, B. Profilaxia antileprosa en paises de pequena endemia. El BCG en la profilaxis de la lepra. Rev. Leprol. Fontilles, 0(6):559-629, 1974.
26. PIMENTA, W.P. Contribution to the study of the nonspecificity of the tuberculin at high concentrations (Palmer and co-workers hypothesis) in patients with lepromatous leprosy and patients affected by other diseases. Ribeirão Preto, 1963. [Thesis - Faculty of Medicine, Ribeirão Preto University] Acta Leprol., (37) :5-66, 1969.
27. REA, T.H.; GOTTLIEB, B.; LEVAN, N. E. Apparently normal skin in lepromatous leprosy. Arch. Dermatol., 111(12) :1571-1574, 1975.
28. REA, T.H.; QUISMORIO, F.P.; HARDING, B.; NIES, K.M.; DI SAIA, P.J.; LEVAN, N.E. FRIOU, G.J. Immunologic responses in patients with lepromatous leprosy. Arch. Dermatol., 112(6) :791-800, 1976.
29. ROTBERG, A. Estudos sobre as reações tuberculínicas na lepra. Rev. Bras. Leprol., 6 (3) :245-272, 1938.
30. ROTBERG, A. Fator: "N" de resistência à lepra e relações com a reatividade lepromínica e tuberculinica. Valor duvidoso do BCG na imunização antileprosa. ("N-Factor" of resistance to leprosy and its relationship with reactivity to lepromin and tuberculin. Doubtful value of BCG in anti-leprous immunization). Rev. Bras. Leprol., 25(2) :25-106, 1957.
31. ROTBERG, A. The influence of allergic factors in the pathogenesis of leprosy. In: PACIFIC SCIENCE CONGRESS, 6th, Berkeley, California, 1939. Proceedings. v.5. p. 977-982.
32. ROTBERG, A. Modern trends in the study of the epidemiology of leprosy. In: PACIFIC SCIENCE CONGRESS, 6th, Berkeley, California, 1939. Proceedings. v.5, p 939-945.
33. ROTBERG, A. "N-Factor/Anergic Margin" or resistance/susceptibility to hanseniasis. I. The foundations of the theory. Hansen. hit., 2(2):115-124, 1977.
34. ROTBERG, A. "N-Factor/Anergic Margin" or resistance/susceptibility to hanseniasis. H. The general acceptance of the theory. Hansen. Int., 2(2) :125-134, 1977.
35. ROTBERG, A. Some aspects of immunity in leprosy and their importance in epidemiology,;, pathogenesis and classification of forms of the disease. Based on 1529 lepromin-tested cases. Rev. Bras. Leprol., 5(n.° esp.) :45-97, 1937.
36. ROTBERG, A.; BECHELLI, L.M.; KEIL, H. The Mitsuda reaction in a non-leprous area. Int. J. Lepr., 18(2) :209-220, 1950.
37. SAHA, K. & MITTAL, M.M. A study of cell mediated immunity in leprosy: changing trends in the immunological spectrum of the disease. Clin. Exp. Immunol., 8(6):901-909, 1971.
38. SAINT-ANDRE, P.; BUENO A.M. Study of tuberculin-type delayed allergy to living bodies. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen. 1973. Transactions apud Int. J. Lepr., 41(4) :562, 1973.
39. SOUZA CAMPOS, N.S.; ROTBERG, A.; BECHELLI, L.M.; GINEFRA, M. Estudos sobre a viragem da lepromino-reação pelo BCG. (III) Resultados da lepromino-reação em coletividade de filhos de hansenianos e tentativas de viragem dos lepromino-negativos, duvidosos ou francamente positivos mediante esquemas variados de
administração da BCG. In: CONGRESSO INTERNACIONAL DE LEPROLOGIA, 8.° Rio de Janeiro, 1963. Anais. Rio de Janeiro, Serviço Nacional de Lepra, 1963. v.3. p. 310-322.
40. TURK, J.L.; & WATERS, M.F.R. Immunological significance of changes in lymph nodes across the leprosy spectrum. Clin. Exp. Imunol., 8:363-376, 1971.
41. WATERS, M.F.R. Significance of the lepromin test in tuberculin-negative volunteers permanently resident in a leprosy-free area. In: INTERNATIONAL LEPROSY CONGRESS, 10th, Bergen, 1973. Transactions apud Int. J. Lepr., 41 (4) :563, 1975.
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1978-11-30
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ROTBERG A. "N-Factor/Anergic Margin" or Resistance/Susceptibility to hanseniasis. 111. The general acceptance of the theory under other names, a few pending questions and the related researches ahead. Hansen. Int. [Internet]. 1978 Nov. 30 [cited 2024 May 20];3(2):122-34. Available from: https://periodicos.saude.sp.gov.br/hansenologia/article/view/36078
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