No evidence of linkage between Mitsuda reaction and the NRAMP1 locus.

Thirty sib-pairs were ascertained through unrelated lepromatous probands. They consisted of 22 healthy individuals and 8 leprosy patients. The Mitsuda reactions of all sibs were evaluated both macroscopically and histologically, and high molecular weight genomic DNA was extracted from the white blood cells of all sib-pairs. Three DNA polymorphisms identified by polymerase chain reaction (274C/T, D543N, 1729 + 55del4) were used as chromosome markers at the NRAMP1 locus. Sib-pair comparisons did not disclose any sign of close linkage between the Mitsuda reaction and the genetic markers.

O estudo da resposta imune em pacientes com infecçäo pelo vírus da imunodeficiência humana (HIV) em relaçäo ao antígeno de Mitsuda / The study of immune reponse in patients with infection by HIV in relation to Mitsuda's pathogen

Os autores apresentam resultados de estudo da resistência à infecçäo hansênica em 22 pacientes HIV positivos do Hospital Universitário Clementino Fraga Filho, da Universidade Federal do Rio de Janeiro, mediado pela correlaçäo clínico-patológica do Teste de Mtsuda e outros parâmetros. A amostragem evidenciou 77% de reaçöes negativas, 13% duvidosas e 9% positivas. A observaçäo histológica da reaçäo de Mitsuda mostrou granuloma tuberculóide em nove pacientes (40%) em diferentes fases de formaçäo, permitindo aos autores concluir que a infecçäo pelo HIV diminui sensivelmente, de forma lenta e graudal, a capacidade dos indivíduos de formarem granuloma tuberculóde e de lisar Baar, jogando-os para uma faixa de menor reatividade defensiva constitucional, mais próxima do pólo virchowiano. Atribuem a disfunçäo básica a alteraçöes do linfócito T colaborador e seus subprodutos, principalmente a interleucina II e o interferon

Blastogenic response with autologous plasma and Mitsuda's reaction in leprosy patients and their unaffected sibs.

Many investigators have evaluated the influence of genetic constitution on the susceptibility to leprosy in studies linked to different types of research. To determine the possible existence of a family trait linked to the lymphoproliferation and to lepromin reactivity we studied the blastogenic response to phytohaemagglutinin, lepromin and M. leprae and the Mitsuda's reaction in leprosy patients and their unaffected sibs. Sixty-eight individuals were studied, 34 were leprosy patients (17 lepromatous and 17 tuberculoid leprosy) and the remaining were their sibs previously matched by sex and age. The indices of blastogenesis and lepromin reactivity were lower in lepromatous than in tuberculoid patients, that confirmed the immunological polarity of the two types of leprosy. Both the lymphoproliferation and Mitsuda's reaction results suggest different cell immune responses in leprosy patients and their unaffected sibs, so that the hypothesis of a family trait favouring the similarity of responses to these tests among sibs becomes unlikely.

Lymphocyte blastogenesis and lepromin reactivity in leprosy patients and their parents.

To determine whether there is an inherited familiar trait linked to the lymphocyte blastogenesis test (LTT), under stimulation with PHA, lepromin and Mycobacterium leprae in culture medium containing autologous plasma, this test was carried out in patients with the polar forms of leprosy and their parents. The lepromin reaction was also studied in the patients and their parents because, since the test is negative in lepromatous (L) patients and a greater proportion of negativity is detected among their relatives, it might be assumed that the lymphocytes of these individuals could have a lower tendency towards blastogenesis than lymphocytes of tuberculoid (T) patients and their relatives. Thirty individuals were studied, ten of them being leprosy patients (4 L and 6 T) and the remaining their parents; 115 LTT, including control and stimulated cultures, were performed. In the limited number of patients and parents studied, the results showed that mothers of either L or T patients displayed a similarly low response to the stimulants M. leprae and lepromin. The lepromin reaction was negative in all L patients and positive in 3 out of 8 parents, as well in all the T cases and their fathers. Fathers and their T descendants were lepromin positive and there was a certain relationship between this reactivity and blastogenesis. This might suggest a possible inherited familiar trait related to a relative degree of resistance. However, further evidences from studies with larger number of subjects are required to support this hypothesis.

A reaçao de Mitsuda seriada na identificaçao das formas reacionais tuberculóide e dimorfa da hanseníase / ?

Estudou-se a reaçao de Mitsuda em 37 pacientes portadores de hanseníase, sendo 18 da forma tuberculóide reacional e 19 da forma dimorfa reacional, sob o ponto de vista clínico, histológico e baciloscópico, com leituras realizadas aos 30, 60, 90, e 120 dias, com o objetivo de se tentar identificar uma forma da outra. A maioria dos pacientes tuberculóides reacionais apresentou reaçao de Mitsuda positiva +. As reaçoes de Mitsuda diminuíram com o tempo nos dois grupos, sendo mais persistentes no grupo tuberculóide reacional. A baciloscopia aos 30 dias foi negativa ou houve presença de raros bacilos em 77,78 por cento dos casos tuberculóides reacionais. Conclui-se que os tuberculóides reacionais possuem uma maior capacidade de clareamento bacilar que os dimorfos reacionais e que a reaçao de Mitsuda pode ser útil na identificaçao dessas duas formas e, inclusive, sugerir sua evoluçao quanto ao diagnóstico e quanto à terapêutica

Analise imunohistoquimica dos nervos cutaneos em reacoes de Mitsuda positivas / Immunohistochemical analysis of the cutaneous nerves in positives Mitsuda's reactions

A histopatologia da reacao de Mitsuda tem sido bastante estudada nas ultimas sete decadas, sob os mais diversos pontos de vista. Pouca atencao tem sido dada, entretanto, ao frequente comprometimento de filetes nervosos cutaneos pelo granuloma que se segue ao inoculo da lepromina, nao havendo uma explicacao definitiva para este fenomeno. A presente tese objetiva testar a hipotese da existencia de um neurotropismo da reacao inflamatoria tardia na histologia da lepromino-reacao, classificar e quantificar as alteracoes histopatologicas encontradas nos nervos envolvidos e verificar se estas alteracoes sao decorrentes da presenca de antigenos micobacterianos em seu interior ou de algum outro fator neural associado. Para tanto, foram estudadas 60 biopsias de reacoes de Mitsuda positivas, atraves de tecnicas de histopatologia convencional e pelo metodo da imunoperoxidase, com a utilizacao de anticorpos anti-proteina S-100 e anti-Mycobacterium bovis(BCG). Filetes nervosos de 4 biopsias foram analisados tambem atraves da microscopia eletronica de transmissao. O estudo evidenciou filetes nervosos em 85,0% da amostra estudada: 98,0% das biopsias com presenca de nervos exibia tendencia neurotropica do infiltrado inflamatorio. A perineurite foi o achado mais frequente, 75,0% das biopsias analisadas, e a endoneurite o mais raro, somente 6,7% dos especimes: 56,7% das biopsias apresentavam nervos indenes circundados pelo granuloma e 58,3% nervos tangenciados pelo mesmo; 40,0% dos especimes evidenciavam nervos inalterados e totalmente afastados do infiltrado inflamatorio. Em geral, diversas destas alteracoes estavam presentes na mesma biopsia, independentemente do tipo de granuloma. Do numero total de 557 filetes nervosos identificados nos especimes, 85,3% apresentavam infiltrado neurotropico (330,3% com perineurite, 29,0% tangenciados pelo granuloma, l5,4% circundados pelo granuloma, 0,9% com endoneurite, e 9,7% ligados ao granuloma mas dificeis de serem classificados) e somente 14,7% nao tinham relacao com o infiltrado inflamatorio. Foi detectado antigeno micobacteriano em 98,3% dos especimes, dentro dos diversos componentes do granuloma, estando ausente em somente uma reacao de Mitsuda Tuberculoide. Normalmente, os filetes nervosos nao apresentaram antigeno micobacteriano em seu interior. Foram demonstrados, entretanto, pequenos depositos deste em 1 perineuro e em 1 celula de Schwann, dos 557 nervos analisados (0,36%), esta ultima de um pac

CD1-positive epidermal Langerhans cells in skin reactions to autologous peripheral-blood-derived mononuclear cells in leprosy patients.

A comparison was made on the characteristics of the infiltrates, the number and distribution of CD1-positive epidermal Langerhans cells (LC) at the sites of skin reaction induced by autologous peripheral-blood-derived mononuclear cells (PBMC) in leprosy patients. Clinically and histologically, the skin reaction was well expressed in tuberculoid patients as compared to lepromatous patients, erythema nodosum leprosum (ENL) patients and contacts. The quantum of lymphocytes in the infiltrates was maximal in the tuberculoid patients and it was minimal in lepromatous and ENL patients. The number and distribution of LC in the tuberculoid patients was significantly higher in the PBMC-inoculated sites as compared to control sites over 24 h. In contrast, no difference in the number and distribution of LC was noticed in the lepromatous and ENL patients. These observations indicate that the lymphocytes of tuberculoid patients in contrast to lepromatous leprosy patients are capable of sustenance in the local micro-environments of the skin and an effective interaction may be possible between LC and PBMC.

A study of the immunological effects of cimetidine in patients with lepromatous leprosy.

To test the capacity of cimetidine to enhance cellular immunity in patients with lepromatous leprosy (LL), cimetidine was given for one month to 29 inactive LL patients and 3 active LL patients. Immune function was monitored with skin tests (lepromin, PPD, candida, and trichopytin), lymphocyte transformation tests (phytohemagglutinin, BCG, and Dharmendra lepromin), and quantitation of peripheral blood lymphocyte subpopulations. A small but significant "booster" response to PPD was the only change observed in the study of patients with inactive disease, and leprosy-related reactions did not occur. In the few active LL patients studied, neither immune enhancement nor leprosy-related reactions were observed. The results of this investigation suggest that cimetidine can be used safely in patients with inactive lepromatous leprosy.

Algunos aspectos de la inmunología de la lepra: segunda parte / Some aspects of leprosy immunology: 2d part

La lepra es una enfermedad multifactorial en la que la función que desempeña la respuesta inmunitaria es preponderante; sin embargo, la inmunología aún no ofrece explicación para la lepra TT, en la que la respuesta inmunitaria celular parece estar intacta. Existen investigaciones que indican que si bien la información genética del huésped no es determinante para el desarrollo de la enfermedad, sí lo es para el tipo de enfermedad que desarrollará el individuo

[Combination of BCG and lepromin in the treatment of leprosy]. / De l'association du BCG à la lépromine dans le traitement de la lèpre.

An unusual principle has been observed: when obliged to reproduce in a new medium ill-adapted to their development, mycobacteria abandon their common mode of reproduction--transversal division--and adopt a mode of evolution that puts less of a strain on their vitality: the long evolutive cycle, first described in 1899. In an initial step, the mycobacilli used for seeding purposes undergo auto-bacteriolysis, creating a cyanophilous fundamental substance which is in fact a symplasm due to the ex-bacillary microgranules, a multitude of independent and mobile genes. These genes merge according to a new and simpler arrangement: thus are formed the slender cocci that take the place of the amorphous cyanophilous substance. These cocci, released in the culture, multiply and lengthen into bacilli which merge to form a new amorphous cyanophilous substance. This new amorphous cyanophilous substance, thanks to another rearrangement of its genes, then forms a "crust" which undergoes exfoliation and crumbles into alcohol-acid-fast (a.a.f.) bacilli. Coryneforms and a.a.f. bacilli (mycobacteria) constitute two distinct agents with different and even occasionally opposite pathogenicities, as can be observed in co-cultures of Coryneforms (Hansen's bacillus or bacillus Calmette-Guérin) and tubercle (Koch's) bacillus. In such co-cultures, the tubercle bacilli progressively lose their vitality and virulence while, inversely, the Coryneforms reinforce their pathogenicity. Co-cultures of BCG and lepromin thus constitute an association with a particular property and most likely an auto-vaccinating activity against leprosy which is the subject of on-going research.

IV. El teste de Mitsuda con lepromina de armadillo de sujetos sanos vacunados y no con la vacuna antituberculosa BCG (+)

El número y la intensidad de reacciones positivas al test lepromínico con el uso de la lepromina A aumentan en las personas vacunadas con el BCG en comparación con los no vacunados. Estos resultados sa basan en el estudio de un total de 3.096 individuos de los cuales 1.399 vacunados con el BCG. Los datos de base son los siguientes: Mitsuda negativos: vacunados con BCG 6,43 por ciento. No vacunados, 37,37 por ciento. Mitsuda positivos con nódulo ulcerado: vacunados con BCG 45,46 por ciento. No vacunados, 11,66 por ciento. Los AA. son de la opinión que la aumentada intensidad de la reacción, causada por el BCG, es de tipo ICM específica. No se puede olvidar que el Micobacterium leprae y el Mycobacterium tuberculosis tienen algunos antígenos en común, por lo tanto, en lugar de deshechar el empleo del BCG como medio de lucha contra le lepra, sería de interés de estudios como se pueda integrar su falta de antigenos específicos frente al M. leprae.

V.- La vacuna BCG y la lepromina de armadillo suministrada contemporaneamente sea en asociación sea separadamente (+)

42 niños de edad comprendida entre 6 y 14 años hans sido sometidos contemporáneamente al test de la lepromina A y la vacunación co BCG. La lectura fue practicada al 30.º día. Los 16 niños que recibieron los dos antígenos conjuntamente en una sola inyección tuvieron todos alo 30.º día una intensa prositividad con nódulos ulcerados. (Un segundo test con sólo lepromina A y estudio de respuesta de los linfocitos T frente al antígeno lepromínico nos dirán cuando el BCG haya influenciado al antígeno inmunizante de la lepromina A en sentido específico).En los niños que recibieron los dos antígenos separadamente se observa que el BCG determina en todos ellos un nódulo ulcerado, mientras que la lepromina A fue negativa en 5 casos y positiva en los restantes 21 casos, dando la ulceración del nódulo en 4 casos. Se hacen consideraciones sobre la influencia qu el BCG puede haber tenido en la respuesta lepromínica y programas para ulteriores estudios.