Reversion of the downhill course of active lepromatous leprosy by repeated transfusions of fresh blood, donated by healthy but lepromin positive patients.

Earlier studies of immunologic reconstitution therapy of active lepromatous leprosy patients by repeated infusions of viable allogeneic blood lymphocytes indicated a beneficial effect. In order to avoid cell separation and its associated risks, we attempted to transfer immunity passively into seven seriously ill lepromatous patients by repeated transfusions of fresh blood donated by healthy, but tuberculin and lepromin positive, subjects. The results showed clinical improvement in some cases with the elimination of Mycobacterium leprae, histological reversion and return of immunologic responsiveness.

Impairment of Jones-Mote hypersensitivity and specific antibody response against depolymerized flagellin in lepromatous leprosy.

Cutaneous hypersensitivity and antibody-producing capacity were assessed in patients with lepromatous leprosy with defective immunity, by immunizing them with monomeric flagellin from Salmonella adelaide. Results were compared with those of controls, matched for age and sex, derived from similar socioeconomic stratum, but without any defect of the immunological system. In contrast to the normal individuals, who showed Jones-Mote type of hypersensitivity, no lepromatous patient could mount any 'delayed-in-time' cutaneous hypersensivivity reaction against an intradermal challenge of monomeric flagellin. However, when immunized through the subcutaneous route, both groups could produce adequate amounts of specific serum antibody. In addition to this unique split tolerance found in all lepromatous patients, some patients showed low levels of 'natural' IgM antibody, reduced formation of specific antibody when immunized through the subcutaneous route, and incomplete maturation of IgG class of anti-flagellin antibody. When immunized by the intradermal route, however, production of both anti-flagellin antibody and maturation of IgG antibody was significantly inhibited in normal adults but not in lepromatous patients. Thus, contrary to the earlier concept of hyperactivity of the humoral immune apparatus in lepromatous leprosy, the present study detected B-cell hypofunction in some patients.

An attempt at passive transfer of immunity to leprosy patients by transfusion of allogeneic lymphocytes, inactivated with mitomycin C.

An attempt was made to repair cell-mediated immunity in 7 patients suffering from lepromatous leprosy and severe erythema nodosum leprosum by intravenous infusion of 400 million allogeneic blood lymphocytes on 3 occasions. The lymphocytes were obtained from lepromin and tuberculin-positive subjects and were inactivated in vitro by treatment with mitomycin C. Immunotherapy with inactivated lymphocytes only modified the severity of erythema nodosum leprosum, without altering other aspects of the disease.

Hepatic lesions in asymptomatic children of leprosy patients.

Forty-two asymptomatic children of leprosy patients were studied for possible hepatic lesions. Hepatic lesions were observed in 47% while acid-fast bacilli in the liver were found in 9.5%. The most frequent lesions encountered included granuloma in 9.5%, focal areas of necrosis in 14%, portal triaditis in 17%, and Kupffer cell hyperplasia in 33%. Occasionally more than one lesion was observed in a biopsy. No correlation with the occurrence of the various hepatic lesions could be made with a history of BCG vaccination or results of skin tests done with tuberculin and lepromin.

Platelet function in leprosy.

In a group of 50 leprosy patients, platelet function tests were found to be abnormal in 44. More than half the patients showed significant impairment in platelet adhesiveness and aggregation to collagen which correlated best with increase in serum IgM levels. ADP-induced aggregation of platelets was not a major defect and Pf-3 availability was reduced only in a fourth of the patients. In vitro incubation of collagen with plasma from leprosy patients significantly reduced its ability to clump normal platelets. This appears to be the first report of defective platelet function in leprosy, and it is thought that such changes may in part be due to increased IgM globulins in the blood and/or to alterations in the collagen brought about thereby.

Immunologic aspects of leprosy as related to leucocytic isoantibodies and platelet aggregating factors.

The incidences of various iso- and autoantibodies in a random population of 112 unselected leprosy patients is presented. Low titers of leucocytic isoantibodies and platelet aggregating factor were detected in the sera of a variable number of such patients. The leucoisoagglutinins were found in 8% of the sera of tuberculoid as well as lepromatous leprosy patients, whereas the leucoisocytotoxins were detected in a larger percentage of the lepromatous (40%) as well as tuberculoid (28%) cases. The platelet aggregating factors (PAF) were positive in 51.2% and 45% of lepromatous and tuberculoid cases respectively. Of the 21 positive sera for PAF, the antiplatelet factor by antihuman globulin consumption test could be demonstrated only in 66.6% and 50% of lepromatous and tuberculoid sera respectively. To study the frequencies of these newly detected antibodies or antibody-like factor and to compare their occurrences with other well-documented autoantibodies present in the sera of leprosy patients: cryoglobulins, antinucleoprotein antibody and thyroglobulin autoprecipitin were also studied in the sera of the same population of leprosy patients. It has been observed that the simultaneous occurrence of all these auto- and isoantibodies in the serum of one patient is a rare phenomenon. Leucocytic and platelet counts of these patients having antibodies against leucocytes and platelets were found to be within normal limits. Accordingly, it is suggested that the low levels of antileucocyte antibody and antiplatelet factor are probably harmless to the hosts. On the other hand, it is postulated that these antibodies may act as enhancing factors by being specifically adsorbed on the lymphoid cells, thus rendering them unresponsive to mitogenic stimulus in vitro. From these studies it seems that leprosy, especially the lepromatous type, is associated with some of the serological features suggestive of an autoimmune aberration.

Passive transfer of immunity into leprosy patients by transfusion of lymphocytes and by transfusion of Lawrence's transfer factor.

About 1,200 million viable lymphocytes from normal but lepromin- and tuberculin-positive human beings were transfused in four patients of lepromatous and one of tuberculoid leprosy three times at monthly intervals. Three patients of lepromatous leprosy suffered from erythema modosum, whereas the other two developed severe reaction whenever put on the smallest dose of dapsone. In one patient of lepromatous leprosy, minimal improvement or none was observed, whereas in the remaining three cases of lepromatous and one of tuberculoid leprosy, clinical, bacteriological, as well as histological improvement occurred. Two of the five patients started to tolerate the dapsone during the period of study. The present study indicates that immunotherapy might have a definite role in the management of the disease especially in cases with erythema nodosum. Lawrence factor, prepared from leucocytes of normal donors, was transfused three times into four lepromatous leprosy patients who were intolerant to anti-leprosy drugs. The donors were healthy but were tuberculin and lepromin (Mitsuda) positive. The clinical, histological, bacteriological (morphological index), and immunological assessments of the patients were performed before and 5 months after starting the immunotherapy. In two patients conversion of Mitsuda reaction occurred, but there was no appreciable improvement in the clinical, histologic, and bacteriologic status of these patients.

Consequences of smallpox vaccination in leprosy patients.

This study illustrates the consequences of smallpox revaccination in 45 lepromatous, 28 tuberculoid, and 47 normal individuals. Results obtained with intradermal inoculations indicated that the patients with leprosy were associated with a relative anergy against the vaccinia virus, the anergy being minimal in the tuberculoid leprosy but marked in the cases with lepromatous leprosy. Major vaccinial reactions were observed more often in patients with lepromatous leprosy than in the controls or patients with tuberculoid leprosy. Furthermore in a patient with lepromatous leprosy, vaccinia necrosum also developed. The smallpox vaccination with live virus also appeared as a provocative factor for the precipitation of lepra reaction in the lepromatous leprosy cases. After 3 weeks of vaccination, the frequency of the specific humoral antibody response was the same in the tuberculoid patients and controls while it was higher in the cases with lepromatous leprosy. The prevaccination titer of total hemagglutination inhibition antibody was significantly higher in the lepromatous leprosy cases. However, the postvaccinial, humoral antibody response of the lepromatous patients was of the same magnitude as that observed in the normal individuals, and it was mainly due to a 2-mercaptoethanol-resistant antibody.

Renal lesions in leprosy

Thirthy patients with lepromatous and nonlepromatous leprosy were studied in respect to their renal lesions and changes in kidney function. In none of the patients were specific lesions of the disease found, nor was Mycobacterium leprae demonstrable in any. The most frequent lesions met with included focal interstitial nephritis, glomerular hypercellularity, tubular degeneration, and hyalinization of smail-sized and medium-sized blood vessels. In addition, three patients showed circumscribed aggregates of mononuclear cells, and one showed chronic pyelonephritis. The affection of the kidney was independent of the duration and the type of leprosy.