Sequential monitoring of 724 sera for antibodies to a neoantigen based on phenolic glycolipid-I (PGL-I) and native lipoarabinomannan (LAM) in 90 leprosy patients undergoing therapy in San Francisco was conducted. Untreated lepromatous patients frequently (91%) had significant antibodies to both moieties. Antibodies were less frequently found in tuberculoid patients (74% to neoantigen and 37% to LAM). In the first 3 years of treatment, average serum antibodies to both moieties fell significantly. Antibodies to LAM fell during each of the first 4 years of therapy, but decreasing antibody levels to the PGL-I neoantigen did not appear to fall consistently after the third year of treatment. A wide variation in the rate of fall of serum antibodies was noted. Sequential changes in the amounts of serum antibodies to the neoantigen and LAM in general paralleled one another but were at times discrepant. Both in San Francisco and Malaysia, skin-smear negative, long-term treated, lepromatous leprosy patients frequently harbored significant antibodies to both PGL-I and LAM.
A detailed account and definition is given of the previously inadequately described "giant reactions" to tuberculin occasionally seen in leprosy patients. The reaction is an accelerated and exaggerated response to species-specific antigens of Mycobacterium tuberculosis found in both PPD and New tuberculin. Our studies were performed in Malaysia, Uganda, Spain, and England. There was a significantly higher incidence of the phenomenon in Malaysia than in the other centers, but this may have been because there alone previously untreated lepromatous (LL and BL) patients were serially tested for up to three years after starting chemotherapy. Of the 28 patients exhibiting giant reactions, 27 occurred among lepromatous patients (24 LL and 3 BL), of which only 3 (1 LL and 2 BL) were untreated. One treated BL patient had developed, and one untreated BL patient was a family contact of, active tuberculosis. Giant reactions are uncommon in untreated and in very long-term treated LL patients, but may occur in up to a fifth of those receiving their first 1-3 years of chemotherapy. Although the mechanism is not yet understood, it appears to be a coincidence of delayed hypersensitivity of the tuberculin type and a less-delayed phenomenon of excessive local edema associated with local lymphadenopathy and short-lasting symptoms of malaise and pyrexia. It is suggested that the majority of giant reactions occur during a period of temporary lack of immune regulation associated with changing levels of antigenic load.
Testicular germinal cell antibodies were found in forty-four out of the fifty-nine patients with lepromatous leprosy and in four out of ten patients with tuberculoid disease. A similar pattern was found in twelve out of 262 control patients and
normal subjects. The antibody was found to be of the IgG class and forty out of forty-nine of these antibodies were shown to be complement fixing. Spermatozoal antibodies were detected in twelve patients, but no ovarian antibodies were found in any specimen. There was no close correlation between erythema nodosum leprosum (ENL) and testicular antibodies. It was found that the characteristic of the testicular antibody in leprosy was its ability to be absorbed by Mycobacterium BCG suspension suggesting that this is another antibody induced by infection. A similar fluorescent pattern was seen in some patients who did not have leprosy, but in these cases it could not be abolished with BCG. It is concluded that autoimmunity may be one of the factors involved in the pathogenesis of orchitis in leprosy.
Study site: MRC Leprosy Research Unit, Sungei Buloh, Selangor, Malaysia.
The response to lepromin and Kveim antigens was compared and studied in 15 leprosy patients who were tuberculin negative. Of the 11 lepromin positive tuberculoid patients, 4 were Kveim positive, 1 was equivocal, and the rest were negative. Of the four lepromin negative lepromatous patients, one gave a positive Kveim test while the other three were negative. It has been shown that false-positive Kveim reactions are found in a higher percentage of South Indian leprosy patients than in those of other backgrounds, such as Japanese and Malaysian Chinese patients. It is also suggested that no definite relationship exists between the reaction of leprosy patients to lepromin and Kveim antigens. We further suggest that the anergy exhibited by lepromatous patients to the antigen of M. leprae is specific, as evidenced by the positive Kveim response in one lepromatous patient.
Kveim tests using a validated material have been undertaken in Malaysia on 39 patients (32 Chinese; 4 Malay and 3 Aboriginal) with lepromatous or tuberculoid leprosy. All the patients had been treated for leprosy, most for two or more years. The tests were read microscopically. Of the 21 lepromatous patients one gave a weak positive and two an equivocal Kveim test whereas four of the nine tuberculoid patients gave equivocal or weak Kveim positivity. Only the tuberculoid form elicits a higher proportion of granulomas than might be expected in a comparable normal population. Of nine patients (8 lepromatous; 1 tuberculoid ) who failed to sensitize well to tuberculin
following two BCG vaccinations, two gave equivocal Kveim tests similar in appearance to those in the other groups.