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Autoantibodies in lepromatous leprosy.

Lepromatous leprosy patients often develop erythema nodusum leprosum (ENL) reactions mainly during treatment of the disease. Hence, this study sought to investigate correlation between the prevalence of certain autoantibodies and ENL reactions in these patients. The patients included in the study were fifty patients with lepromatous leprosy and a similar number of normal controls. Sera were collected from the patients and normal controls and the prevalence of circulating rheumatoid factor antinuclear and antismooth muscle antibodies was determined. The prevalence of autoantibodies was increased in lepromatous leprosy as compared with normal controls. The prevalence of these autoantibodies were affected differently by the ENL reactions. ENL lepromatous leprosy showed a slight decrease in prevalence of antinuclear and antismooth muscle antibodies, whereas there was a slight increase in the prevalence of rheumatoid factor in ENL lepromatous leprosy. The levels of serum immunoglobulins tended to show a decline towards ENL lepromatous patients compared with the uncomplicated lepromatous patients. The significance of these finding is discussed in relation to their possible role in the pathogenesis of ENL reaction. It is concluded that some of these autoantibodies and immunoglobulins may be utilized during ENL reactions in the formation of immune complexes.

Journal Article↗

A single skin lesion--an unusual presentation of lepromatous leprosy.

Lepromatous leprosy presenting as a solitary lesion with a high bacterial count is a rare occurrence. Such a case has been followed at the National Hansen's Disease Center, Carville, Louisiana, U.S.A., since 1977. The lesion was located on the left elbow and had been present for about nine months. The bacterial index in the lesion was 5+ and the morphological index was 0%, but slit-skin smears elsewhere were negative. The histopathology of the lesion was that of subpolar lepromatous leprosy, and the lepromin skin test was negative. Growth of the organism in the mouse foot pad was characteristic of Mycobacterium leprae, and the patient's response to dapsone monotherapy has been excellent. Therefore, this patient with a single skin lesion has lepromatous leprosy histologically, immunologically, and bacteriologically. This case illustrates the importance of slit-skin scrapings and biopsy in new cases with unusual lesions and, secondly, suggests that there are factors yet undetermined which play a significant role in determining host response to M. leprae.

Biopsy↗

Light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL).

Cutaneous branches of radial nerves in patients with lepromatous leprosy (LL) and borderline lepromatous (BL) were studied by light and electron microscopy. Foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. In the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. Vacuolated Schwann cells were also found in the nerve fasciculus. In electron microscopy, these foamy macrophages and vacuolated Schwann cells contained numerous small dense materials, irregular in size and shape, considered to be degenerated and fragmented mycobacterium leprae. These dense materials were found also in the cytoplasm of vascular endothelial cells. These findings suggest that mycobacteria enter into the endoneurium via the blood vessels. In our present study, on the other hand, it was very difficult to find the intact mycobacteria in the cytoplasm of the foamy macrophages, Schwann cells or endothelial cells, as well as in the Ziehl-Neelsen staining of paraffin sections. The disappearance of intact bacilli in our present study might have been caused by multi drug therapy. The myelinated nerve fibers were degenerated and disappeared in variable degrees. Degenerative changes of the myelin sheath developed from the outer layer to the inner layer with disarrangement of the lamellar structure. These findings were different from myelin destruction of peripheral nerves in Wallerian degeneration. The degenerative changes of the myelin sheath are caused by degeneration and destruction of Schwann cells in leprosy patients. Fibrosis surrounding myelinated and unmyelinated nerve fibers, i.e., periaxonal fibrosis, was found to a greater or lesser extent in the endoneurium. In the present study, it is still unclear whether the periaxonal fibrosis was due to necrosis of the Schwann cells by infection of mycobacteria or to an autoimmune mechanism such as antiperipheral nerve antibody. However, lamellated concentric fibrosis surrounding regenerative myelinated and unmyelinated nerve fibers with the disappearance of mycobacteria suggests that degenerations and regenerations of nerve axons were repeated during clinical cause. These findings indicated that autoimmune mechanisms play an important role in the pathogenesis of periaxonal fibrosis.

Adolescent↗

Histopathological study of apparently normal oral mucosa in lepromatous leprosy.

In lepromatous leprosy, it may be postulated that apparently normal areas of skin are the probable sites of future extension of the pathological process and the events taking place in these site might represent the earlier stages of such an extension. Thus the present study has been done to evaluate any such changes in the apparently normal oral mucous membrane of the lepromatous leprosy patients, since oral involvement is common in these patients. Twenty two cases of lepromatous leprosy were studied histologically to see changes in apparently normal oral mucosa. Out of the 22 patients, apparently normal skin biopsies were taken from 13 patients and 5 lesional biopsies were taken from the same patients. Apparently normal oral mucosal biopsies were done for all patients. Biopsies of 22 cases of apparently normal oral mucosa did not show granulation formation of acid-fast bacilli histologically. The only change present was mild inflammation.

Cheek↗

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.

Adult↗

Failure to induce delayed-type hypersensitivity to Mycobacterium leprae in long-term treated lepromatous leprosy patients.

Lepromatous leprosy (LL) patients whose bacillary load has decreased to almost undetectable levels by long-term chemotherapy failed to develop delayed-type hypersensitivity (DTH) to Mycobacterium leprae antigen following immunization with killed armadillo-derived M. leprae. When these LL patients were immunization with killed armadillo-derived M. leprae. When these LL patients were immunized with killed M. leprae in a mixture with live BCG, only DTH to purified protein derivative (PPD) was induced. These results are further evidence that immunological unresponsiveness to the leprosy antigen of patients with lepromatous leprosy is antigen-specific and non-reversible.

Antigens, Bacterial↗

[Effect of L-tetramisol associated with rifampicin in patients with lepromatous leprosy. L-tetramisol in patients with lepromatous leprosy].

In this work are presented results obtained in the treament of thirty patients suffering of lepromatous leprosy. In a group of fifteen patients L-tetramisol was administrated in association to antimocrobian drugs. The control group received only the last medication. Immunological modifications were not observed in any case. However, in six patients treated with L-tetramisol associated to rifampicin during three months it was possible to observe a notable improvement of the clinical state. In the patients that received L-tetramisol associated to other drugs or in those that received only antimicrobian drugs the clinical improvement was very low or null.

Adolescent↗

Immunological changes observed in indeterminate and lepromatous leprosy patients and Mitsuda-negative contacts after the inoculation of a mixture of Mycobacterium leprae and BCG.

This investigation was carried out to study the possibility of eliciting favourable immunological changes in small groups of Mitsuda-negative patients with indeterminate leprosy, lepromatous patients who were bacteriologically negative after prolonged treatment with sulphones, and in Mitsuda-negative contacts by means of stimulation with a mixture of autoclaved tissues from Mycobacterium leprae-infected armadillos and living BCG. A radical change was observed in the specific immunological activity of the indeterminate group, all of whom initially had occasional bacilli in cutaneous nerves in biopsies taken from hypopigmented spots, and in the persistently Mitsuda-negative contacts. The 48 hr and 30 day reactions to lepromin, the 48 hr reaction to supernatant antigen from lepromin, the test for bacillary clearence and in vitro lymphocyte transformation (LTT) to M. leprae from human and armadillo lesions all became positive. Of the lepromatous patients studied, only one became positive to all the criteria mentioned above. In the others, the 48 hr reaction to supernatant antigen, the LTT to antigen from a humn source, and the clearance test remained negative, while the Fernandez and Mitsuda reactions became positive. These results are discussed in terms of the possible use of this stimulation procedure in the prevention and immunotherapy of leprosy.

Adolescent↗

Undernutrition in lepromatous leprosy. V. Severe nutritional deficit in lepromatous patients co-infected with pulmonary tuberculosis.

We have compared the nutritional status of patients with lepromatous leprosy coinfected with pulmonary tuberculosis (18 cases) with that of lepromatous leprosy (239 cases) and of pulmonary tuberculosis (21 cases) and with that of healthy controls. There was a severe weight loss and reduction of skinfold thickness in the patients with pulmonary tuberculosis as well as in lepromatous patients with associated pulmonary tuberculosis, but not in patients with lepromatous leprosy. Levels in sera of diet-dependent proteins, such as albumin, prealbumin and retinol binding protein, were significantly decreased in all three groups of patients; on the other hand, levels of the diet-independent proteins, such as the immunoglobulins, were raised in all the groups, particularly in the pulmonary tuberculosis patients as compared with healthy controls. Serum transferrin levels were decreased only in the tuberculosis patients with or without lepromatous leprosy, but not in patients with leprosy alone. While haemoglobin levels decreased in all patient groups, serum iron concentrations were reduced most in lepromatous patients concomitantly infected with pulmonary tuberculosis. Serum ferritin levels increased in the sera of pulmonary tuberculosis and lepromatous leprosy patients, but was severely reduced in lepromatous patients with associated pulmonary tuberculosis. Mean serum zinc and calcium levels were decreased in all three groups of patients, while the serum copper concentration was increased in all of them compared with healthy controls. Also, inorganic phosphorus was elevated in tuberculosis and lepromatous patients coinfected with pulmonary tuberculosis, but not in lepromatous patients. Serum calcitonin levels were increased in all patient groups indicating an inverse correlation between serum calcium and calcitonin levels. This is the first comparative report describing the status of macro- and micronutrients in two most important mycobacterial diseases of the third world countries.

Adolescent↗

Immunoreactivity in vitro to human testis in patients with lepromatous leprosy.

Patients with lepromatous leprosy and tuberculoid leprosy, together with normal aged matched controls, were tested for in vitro immunoreactivity against a panel of soluble extracts prepared from normal human tissues. The panel consisted of a soluble homogenate of human testis as well as two partially purified fractions of this extract, and control extracts from other human tissues. Immunoreactivity was assessed by extract induced peripheral blood lymphocyte (PBL) transformation, leucocyte migration inhibition (LMI) and leucocyte adherence inhibition (LAI). Although no difference in PBL transformation, LMI, or LAI was obtained between the groups with the control tissue extracts, significant reactivity was obtained for the patients with lepromatous leprosy in at least one of the in vitro tests, when one of the testis extracts was used (Mann-Whitney test). No such reactivity to the testis extracts was obtained in the patients with tuberculoid leprosy or the normal control subjects. Of the twenty-two patients studied with lepromatous leprosy, thirteen had clinical evidence of testicular disease and nine of these patients had raised PBL transformation and LAI reactivity to the testis extracts. This finding of immunoreactivity against testicular extracts in a significant number of patients with lepromatous leprosy by at least one of the vitro tests used, suggests that the associated in vivo testicular atrophy that occurs in these patients may have an auto-immune basis.

Adolescent↗

Serum IL-1ra is elevated in lepromatous leprosy patients.

Patterns of production of specific cytokines are accepted as standards for T-lymphocyte subsets in diseases caused by intracellular parasites. These lymphocyte subsets (Th1 and Th2) have been associated with the different poles of the leprosy spectrum. Lepromatous leprosy (LL) onset correlates with cytokines produced by Th2 cells on the grounds of the patient's poor cellular immune response, i.e., interleukin 2 (IL-2) and gamma interferon (IFN-gamma) deficiency. On the other hand, tuberculoid leprosy (TL) has been associated with a Th1 response. Moreover, pro-inflammatory cytokines like IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) play a major role in chronic inflammatory pathologies being IL-1ra and TNF-alpha soluble receptors, natural counterbalancing inhibitors. In light of this background, we decided to measure serum levels of IL-1 beta, IL-1ra, TNF-alpha and IL-6 in LL and TL patients, and we also studied the production in vitro of Th1 (IFN-gamma, IL-2), Th2 (IL-4, IL-10) and TNF-alpha cytokines. Our data showed that IL-1ra is highly elevated in sera from LL patients; there were no differences in Th2 cytokine levels and there were diminished levels in Th1 cytokines.

Adult↗

Tetanus in patient with lepromatous leprosy (I).

Tetanus in lepromatous leprosy is rare and reported occasionally as case reports only. We present a case of lepromatous leprosy who succumbed to death due to rapidly progressing tetanus. The mechanism of protection from tetanus in leprosy is discussed.

Adult↗

Comparative study of the 48-hour response to soluble antigens obtained from human and armadillo leprosy material in lepromatous leprosy patients and normal persons, contacts of leprosy patients.

We prepared antigens by precipitating with 80% ammonium sulfate supernatants of human and armadillo antigen at a concentration of 160 X 10(6) bacteria per ml. The precipitate was resuspended, dialyzed and filtered. The antigen obtained was inactivated with trypsin during 30 minutes. The tests made with these antigens were negative for the 48-hour test in lepromatous patients and highly positive in normal persons who were contacts of leprosy patients.

Animals↗