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PubMed1993

Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy.

A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy.

Adult↗
PubMed2006

Comparative cytomorphology of skin, lymph node, liver and bone marrow in patients with lepromatous leprosy.

OBJECTIVE: The aim of this study was to compare the cytological changes in skin, lymph nodes, liver and bone marrow in patients with lepromatous leprosy. METHODS: Skin lesion, lymph node, liver and bone marrow aspirates were analysed. May-Grunwald-Giemsa (MGG) and Ziehl-Neelsen (Z-N) stains were employed. Comparative cytomorphology was studied. RESULTS: Twenty patients with lepromatous leprosy were studied. Lepra cells (LC) predominated in the skin aspirates of 12 patients with lepromatous leprosy (LL), lymphocytes accompanied LC in eight patients with borderline-lepromatous (BL) leprosy. Three patients of LL leprosy and two of BL leprosy in type 2 reaction additionally had numerous neutrophils. Two patterns of lymph node aspirates were seen: partial replacement with few LC in a reactive lymphoid background (10), complete replacement with either only LC or LC in a background of degenerating neutrophils (10), the latter a feature of type 2 reaction. Liver aspiration was performed in seven patients and of bone marrow in eight patients. Occasional LC were present in five liver-aspirated patients, steatosis and Kupffer cell hyperplasia in four patients, and myelopoiesis in two patients. Bone marrow smears invariably had occasional LC and a relative increase in mature plasma cells; sea-blue histiocytes were seen in six patients. CONCLUSION: Lepra cells predominated in skin and lymph node aspirates with complete replacement. In comparison, liver, bone marrow and lymph node aspirates with partial replacement were dominated by a preponderance of cells native to these organs with only few or occasional LC.

Adolescent↗
PubMed2005

High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patients.

BACKGROUND: Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. PATIENTS AND METHODS: In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. RESULTS: Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8.11, 95% confidence interval: 1.4-48.2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. CONCLUSIONS: A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae.

Adolescent↗
PubMed1994

IgG humoral response against the antigen 85 complex homologues in leprosy.

Antigen 85 complex is the major protein component present in M. bovis BCG culture filtrate (CF). It consists of a family of three proteins: 85A, 85B and 85C. Combining isoelectric focusing and Western blot analysis, we have previously identified different antigenically related proteins present in the CF of other mycobacteria (M. tuberculosis, M. kansasii, M. avium, M. gordonae, M. fortuitum and M. phlei) using monoclonal antibodies (MoAbs) directed against the antigen 85 complex of M. bovis BCG. Humoral immune response directed against these cross-reactive homologues was analysed in sera from 20 patients with multibacillary leprosy (BL/LL), from 20 patients with paucibacillary leprosy (BT/TT) and from 15 healthy leprosy contacts. All the antigen 85 homologues identified in the seven CFs by MoAbs were also recognized by IgG present in sera from multibacillary leprosy patients, but not or very faintly in sera from paucibacillary leprosy patients or from healthy subjects. These results suggest that some of the M. leprae epitopes inducing a significant humoral response in multibacillary leprosy are common to the various 85 antigenically related proteins present in all mycobacterial species.

Antibodies, Bacterial↗
PubMed1989

T lymphocyte subsets in leprosy. A study of 24 Egyptian patients.

Phenotypic analysis was done on 24 Egyptian leprosy patients and 11 healthy controls. The type of leprosy, duration of disease at the time of testing, and age were found to affect T cell subset distribution. As compared with controls, neural leprosy tended to have a decreased total T cell percentage, borderline leprosy an increased T suppressor cell percentage, and reactional borderline leprosy an increased T helper/suppressor ratio. Patients with the disease for less than 1 year had a higher mean percentage of T suppressor cells and a lower mean T helper/suppressor ratio than patients with leprosy for more than 1 year. The same was true in older (50-70 years old) versus younger (12-41 years old) patients.

Adolescent↗
PubMed1995

Immunohistochemistry in histoid leprosy.

BACKGROUND: Histoid leprosy is a rare form of multibacillary leprosy as the result of secondary or even primary resistance to dapsone. The etiopathogenesis has not been clarified up to now. METHODS: An immunohistochemical study was carried out for the expression of various markers on epidermal and dermal cell populations using sections of frozen skin specimens from 5 patients with histoid leprosy as compared to specimens from 7 tuberculoid and 7 lepromatous patients. RESULTS: Dendritic epidermal cells, identified by monoclonal antibodies against CD1, HLA-DR, CD45, and CD36, were found reduced in histoid leprosy as compared to both tuberculoid and lepromatous groups. A gradual reduction of keratinocytic HLA-DR expression from tuberculoid to lepromatous to histoid leprosy was observed. The pattern of CD36, CD4, and CD8 expression of lymphomonocytic cells in the dermis of histoid lesions was similar to that of tuberculoid leprosy, but without the formation of an organized granuloma. CD45+ cells as well as activated lymphocytic cells, expressed by the activation immunophenotype (CD1, HLA-DR, CD25, CD71, EGF-R) were found frequently in all groups. CONCLUSIONS: The in situ immunohistochemical findings support a modified hypersensitivity reaction of the cellular type that results in an inhibition of the lesional expansion, but not in the destruction of the bacilli within the histoid lesion.

Aged↗
PubMed1981

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↗
PubMedDate not supplied

Monocytes of distinct clinical types of leprosy are differentially activated by cross-linking class II HLA molecules to secrete IL-12.

Leprosy is characterized by a wide spectrum of clinical features depending on the individual differences in Th1-type immunity. The objective of this study was to evaluate whether monocyte activation by stimulus via class II HLA molecules would be correlated with the differences in cellular immune responses among diverse clinical forms of leprosy. IL-1beta and IL-12 productivity in monocyte preparations obtained from PBMCs was estimated in patients with lepromatous- and tuberculoid-type leprosy. We found that monocytes from lepromatous patients produced significantly higher (about 4-fold higher) amounts of IL-12 as compared to in patients with tuberculoid type of leprosy when class II HLA molecules were cross-linked with anti-HLA class II antibodies, whereas almost equal amounts of IL-1beta were produced from each monocyte preparation by stimulus via class II HLA molecules regardless of the clinical form of leprosy. These results suggest that monocyte activation differs between lepromatous and tuberculoid patients in terms of IL-12 secretion, which might be related to individual differences in the cellular immune responses according to the clinical type of leprosy.

Cytokines↗
PubMed1979

In vitro synthesis of humoral factors (immunoglobulins and complement) in lesional skin of leprosy patients.

An in vitro culture technique was used to demonstrate the synthesis of immunoglobulins and complement in lesional skin of patients representing the entire clinico-histopathological spectrum of leprosy. The results indicate that immunoglobulin G is produced in different amounts in the various forms of leprosy. Classification of the patients according to the three main groups shows that a small amount of immunoglobulin G synthesis occurred in tuberculoid leprosy, a distinct amount occurred in borderline leprosy, and large amount occurred in lepromatous leprosy. Contrary to expectation, synthesis of C3 was found only in some of the cultures of these three forms of leprosy. The function of the locally synthesized immunoglobulin G and the findings concerning C3 synthesis are discussed.

Adolescent↗
PubMed1994

Sera of leprosy patients with type 2 reactions recognize selective sequences in Mycobacterium leprae recombinant LSR protein.

Type 2 reactions (erythema nodosum leprosum [ENL]) are episodic, reactional states causing significant morbidity in lepromatous leprosy patients. With a view to defining the immunological differences between the stable and reactional forms of lepromatous leprosy, we determined antibody responses to LSR, a recombinant protein of Mycobacterium leprae previously described by us (S. Laal, Y.D. Sharma, H.K. Prasad, A. Murtaza, S. Singh, S. Tangri, R. S. Mishra, and I. Nath, Proc. Natl. Acad. Sci. USA 88:1054-1058, 1991), as well as to 10- to 15-mer overlapping peptides synthesized on the basis of the LSR amino acid sequence. We report here the selective recognition of B cell epitopes by sera from patients with ENL as compared with a control group with nonreactional lepromatous leprosy. Peptides 2 and 3, with the sequences GVTYEIDLTNKNAA and IDLTNKNAAKLRGD, respectively, were recognized by > 95% of sera from patients with active ENL. Peptide 3 in addition showed reactivity with sera taken from 91.6% of lepromatous leprosy patients who were apparently stable but who were recorded to have had ENL several weeks before or after the sample collection. The core sequence IDLTNKNAA common to both these peptides may be a major target of humoral responses in ENL. In addition, the RGD motif at the C terminus appeared to influence the antigenicity of peptide 3 in enzyme-linked immunosorbent assay. It would appear that humoral responses during ENL are directed to selective antigenic determinants of the leprosy bacillus. The use of such serological markers to identify lepromatous leprosy patients with a high risk for developing ENL would be of clinical and predictive value.

Antibodies, Bacterial↗
PubMed1973

Host responses to Epstein-Barr virus and cytomegalovirus infection in leprosy.

A study was undertaken in patients with leprosy to assess the contribution of cell-mediated immunity to the host response to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection. Sixteen of 72 patients (22%) with lepromatous leprosy, with impaired cellular immunity, had anti-EBV titers of 1,640 or higher. Only 4 of 49 patients (8%) with tuberculoid leprosy, with intact cell-mediated immunity, attained the level of 1:640. The anti-EBV antibody titers were significantly higher in patients with lepromatous leprosy (P approximately 0.025). No significant differences were found in the level of anti-CMV antibody titers in patients with the two types of leprosy. The presence of high anti-EBV antibody titers in lepromatous leprosy suggests that cell-mediated immunity is a significant factor in host response to EBV infection. Host immune responses should be taken into consideration when assignment of an etiological role to EBV is based upon seroepidemiological data.

Antibodies, Viral↗
PubMed1975

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.

Adolescent↗
PubMed1990

Detection of Mycobacterium leprae antigens in the sera of leprosy patients by sandwich immunoradiometric assay using monoclonal antibodies.

An immunological technique for demonstration of Mycobacterium leprae antigen in sera was developed by using specific as well as cross-reactive monoclonal antibodies. The sandwich immunoradiometric assay which we developed is a simple, robust assay that is sensitive to the nanogram level. Sera from 72 leprosy patients were screened for the presence of antigen by this assay. A total of 69% of untreated tuberculoid leprosy patients showed 35-kDa antigen positivity, and 45% of these patients showed anti-35-kDa antibody positivity. Consistently higher antigen positivity rates for the 35-, 12-, and 30- to 40-kDa components of M. leprae were observed in lepromatous leprosy patients than in tuberculoid leprosy patients. During the course of therapy the antigen positivity rate gradually declined, and the antigen could not be detected in any of the 15 patients with subsided cases of leprosy. As antigen is presumably in excess before the antibody response is evoked, our experimental approach for antigen detection is likely to be useful by itself or along with antibody detection for diagnosis of early leprosy.

Antibodies, Bacterial↗
PubMed2005

Prevalence and causes of blindness and low vision in leprosy villages of north eastern Nigeria.

AIMS: To determine the prevalence and spectrum of ocular pathology, and the prevalence and causes of blindness and low vision in leprosy villages of north eastern Nigeria. METHODS: People affected by leprosy, aged 30 years and above, resident in eight leprosy villages were invited to participate. Ocular examination was undertaken of each consenting individual. RESULTS: 480 people were examined. 456 (48%) of 960 eyes had at least one ocular lesion, but only 37% of all lesions were leprosy related and potentially sight threatening. The prevalence of blindness (VA<3/60 with available correction) was 10.4%. An additional 7.5% of subjects were severely visually impaired (3/60< or =VA<6/60). Cataract was the commonest cause of blindness. Other major causes were non-trachomatous corneal opacity and trachoma. CONCLUSIONS: Blindness and low vision are highly prevalent among leprosy patients in this setting. Only a third of the burden of ocular pathology is related to the direct effects of leprosy. Efforts to reduce the backlog of cataract and trichiasis, to improve early detection and management of lagophthalmos, and to provide refractive services are urgently required.

Adult↗
PubMed1995

Harnessing the strengths of the leprosy programme to control tuberculosis.

Tuberculosis remains a leading cause of death in Ethiopia but there is no effective national tuberculosis control programme. By contrast, the leprosy control programme has been very successful, with a 10-fold reduction in the number of leprosy cases requiring antibacterial treatment, though patients with nerve damage require continuing care. The paradox of rising numbers of tuberculosis cases and declining numbers of leprosy cases may be solved by joint leprosy-tuberculosis clinics. The strengths of leprosy fieldworkers in control management, case holding, and compliance can be harnessed in developing an effective tuberculosis control programme. Implementing a joint programme in Ethiopia may be beneficial not only for tuberculosis patients but also for leprosy patients, who are thus brought closer to general medical services.

Ethiopia↗
PubMed1977

Teased fibre study of early nerve lesions in leprosy and in contacts, with electrophysiological correlates.

A teased fibre technique was used to study 19 biopsies of the index finger branch of the radial cutaneous nerve of leprosy patients and contacts. These were compared with four normal nerves. Five nerves were from patients with preclinical nerve lesions, five from leprosy patients with minimal sensory nerve impairment, and five from contacts of lepromatous leprosy. The extent of demyelination in preclinical nerve lesions in leprosy and in contacts of leprosy is recorded. The usefulness of nerve conduction velocity studies in early leprosy patients and in contacts is discussed.

Adolescent↗
PubMed1978

Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia.

In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.

Abscess↗
PubMedDate not supplied

Alpha-1-antichymotrypsin is not associated with the increased frequency of apolipoprotein-E-epsilon-4 allele in elderly non-demented leprosy patients.

In our previous study, elderly leprosy patients showed a low prevalence of senile dementia of the Alzheimer type, but the frequency of apolipoprotein E (APO-E) epsilon 4 was elevated in non-demented elderly leprosy patients. Recent study has shown that Alzheimer's disease risk associated with APO-E epsilon 4 is significantly increased by the alpha 1-antichymotrypsin (ACT) genotype AA. Therefore we examined an association between ACT polymorphism and the APO-E epsilon 4 allele in 350 leprosy patients. None of our data showed an association of ACT genotype and APO-E epsilon 4 allele in leprosy patients. The allelic frequencies of the ACT gene did not differ even between demented patients with leprosy and age-matched controls. Our present data suggest that ACT polymorphism is not associated with the increased frequency of APO-E epsilon 4 in leprosy patients.

Adult↗