Borderline Tuberculoid Patients Research Articles

Comparison of Serum Levels of Interleukin 17 and Interleukin 9 in Leprosy Patients with and without Lepra Reaction: A Cross-Sectional Analytical Study from Central India.

New pathways of host defence have emerged in leprosy, such as T helper (Th) -17, Th-9, T regulatory cells, and other factors like transforming growth factor-beta, etc. Interleukin (IL) 17 produced by Th17 cells has been found to be elevated in lepra reaction, especially type 2 lepra reaction (T2R). Role of IL-9 has not been studied widely in leprosy reactions so far. The study aimed to compare serum levels of IL-17 and IL-9 in leprosy patients with and without lepra reaction. This was a cross-sectional analytical study including untreated adult leprosy patients with and without lepra reaction. A total of 65 patients were included in the study with 30 leprosy patients without reaction and 35 with lepra reaction. Serum levels of IL-17 and IL-9 were measured in these patients using direct enzyme-linked immunosorbent assay and were compared. Borderline tuberculoid (BT) leprosy with type 1 and Lepromatous (LL) leprosy with T2R patients showed significantly higher levels of IL-17 than BT and LL leprosy patients without lepra reaction, respectively. LL patients with T2R showed significantly lower levels of IL-9 than lepromatous cases without reaction. IL-9 levels were higher in BT patients with T1R as compared to BT patients without reaction but the difference was not significant. We found evidence in support of role of IL-17 in the pathogenesis of T2R, which might serve as useful serum markers for the same. IL-17 might have a role in BT leprosy with T1R. IL-9 seems to have a protective role in T2R as opposed to IL-17, working in synergism with Th1 cytokines.

Leprosy patients with deformities at post-elimination stage: The Bangladesh experience.

BackgroundDisability assessment in leprosy patients is a very important factor in the evaluation of the effectiveness of a leprosy elimination program. Little information exists on deformities in leprosy patients in Bangladesh.ObjectivesTo describe the pattern and prevalence of deformities in leprosy patients after leprosy has been declared eliminated from Bangladesh in 1998.MethodsA descriptive retrospective cross‐sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients for the period 2004–2013.ResultsOut of 670 leprosy patients, 213 (31.79%) had deformities. The prevalence of deformity was for grade 1: 92 (43.20%), for grade 2: 121 (56.80%). Among the patients with deformity, males 144 (67.60%) outnumbered females 69 (32.40%). Four age groups were considered. The calculated age‐specific cumulative detection rates showed the highest case detection in >40 years group at 81 (38.02%). The rate of children (<14 years) was less at 7 (3.29%). Of the 213 patients with deformity, the borderline tuberculoid patients were totalled 79 (37.08%), which was higher than other forms of leprosy. Among the 121 patients with limb deformity, 57 (8.50%) had claw hand followed by wrist drop 31 (4.63%), foot drop 30 (4.48%). Three (0.45%) had a nerve abscess, 27 (4.02%) had a trophic ulcer and 7 (1.05%) patients had ocular complications.ConclusionThe grade 2 deformities among newly detected leprosy patients were still high. Claw hand was the most common deformity in the upper limbs, whereas foot drop and trophic ulcer were the most common deformities in the lower limbs. Although leprosy according to the World Health Organization has been eliminated globally, the disease continues to be a significant cause of peripheral neuropathy, deformity, disability and disfigurement in some developing countries like Bangladesh.

Expression of annexin-A1 in blood and tissue leukocytes of leprosy patients.

INTRODUCTION In leprosy, immune system mediators that regulate the infectious process act in a complex manner and can lead to several clinical outcomes. To understand the behavior of these mediators we quantified the expression of annexin-A1 (ANXA1) in the peripheral blood and plasma as well as tissue leukocytes in all clinical forms of leprosy and compared with healthy controls. METHODS Seventy healthy controls and 70 patients with leprosy, tuberculoid (TT) (n = 13), borderline tuberculoid (BT) (n = 15), borderline borderline (BB) (n = 13), borderline lepromatous (BL) (n = 15), and lepromatous leprosy (LL) (n = 14), were selected. Phenotyping of the lymphocyte cells and the intracellular expression of ANXA1 in leukocytes was performed by immunofluorescence. Plasma protein levels were determined by enzyme-linked immunosorbent assay. RESULTS Histiocytes and CD4+ and CD8+ T cells in the skin of BL and LL patients had higher ANXA1 expression. ANXA1 expression was also high in circulating polymorphonuclear, monocytes, and CD4+ and CD8+ T cells in the blood of LL patients compared to those of TT, BT, BB, and BL patients, and these levels were similar to those in healthy controls. Plasma ANXA1 levels indicate an increase in paracrine release in patients with LL. CONCLUSIONS The data indicate that ANXA1 expression is enhanced in the leukocytes and plasma of patients with LL, and may contribute to the inhibition of leukocyte action, leading to inadequate functioning of the immune system and thus contributing to the spread of M. leprae infection.

Role of Histopathology in Predicting type 1 Lepra Reaction in Borderline Tuberculoid Leprosy.

Context:Lepra reactions if not managed promptly are an important cause of sudden onset nerve palsy and disability due to leprosy.Aim:To evaluate the usefulness of histology in predicting type 1 lepra reaction.Setting and Design:After obtaining clearance from institutional research and ethics committees, all histologically proven borderline tuberculoid patients diagnosed at our center from 1.8.2016 to 31.7.2018 were included in this retrospective cross-sectional study.Method:Clinical details were collected from patient records. The pathologist who was blinded to clinical evidence of type 1 lepra reaction at the time of biopsy re-evaluated the histopathology slides for evidence of type 1 reaction. The data of individual patient was analyzed to identify those who had a type 1 reaction at the time of the biopsy or who developed a lepra reaction during follow up.Statistical Analysis Used:Association between histological evidence of type 1 reaction and clinical manifestation of the same subsequently, was assessed using Pearson's Chi square test.Results:Study group comprised of 22 females and 18 males. Clinicohistological concordance was noted in 27 patients (67.5%). Subclinical type 1 reaction was documented in 11 patients (27.5%) based on histopathology evaluation. Five (45.5%) of these 11 patients subsequently developed clinical features of type 1 reaction. This was found to be statistically significant (P value 0.02).Limitations:Main limitation was the small sample size.Conclusions:Histology could serve as a useful tool in predicting future type 1 lepra reaction.

Increased expression of interleukin-17A in the lesional skin indicates increase of serum antibody anti-phenolic glycolipid-I in leprosy patients

Background: In lepromatous type of leprosy, the serum titer of the antibody against phenolic glycolipid (PGL)-I-a-specific antigen in leprosy that is produced by B cell is high. Whereas, the interleukin (IL)-17A expressed by T-helper 17 cells could induce B-cell differentiation. The role of IL-17A in leprosy is still unknown. Hence, this study aimed to assess a correlation between IL-17A expression in the lesional skin and anti-PGL-I immunoglobulin (Ig) M serum levels in leprosy patients. Methods: This study was performed in Leprosy Clinic, Dr. Hasan Sadikin Hospital Bandung, Indonesia, using a cross-sectional analytical study. A punch biopsy obtained from 49 leprosy patients was included through consecutive sampling for measurement of IL-17A expression in the skin by immunohistochemistry scoring (histoscore). Furthermore, the anti-PGL-I IgM level in serum is evaluated by enzyme-linked immunosorbent assay. Results: The IL-17A expressions in the skin biopsies of tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous leprosy (LL) patients using histoscore were 1.00, 2.31, 4.63, 5.06, and 10.14, respectively, and they showed significant differences ( P = 0.0001). The titer of anti-PGL-I IgM levels was 89 pg/ml, 555 pg/ml, 1.244 pg/ml, 1.920 pg/ml, and 23.591 pg/ml in TT, BT, BB, BL, and LL patients, respectively, and they showed significant differences ( P = 0.005). The results of Rank–Spearman correlation analysis between IL-17A expression in the skin and anti-PGL-I IgM serum levels were as follows: r = 0.767 and P = 0.0001. Conclusion: These results suggested that the increase of IL-17A expression in the lesional skin indicates the increase of anti-PGL-I IgM serum levels in leprosy.

A rapid ELISA for the diagnosis of MB leprosy based on complementary detection of antibodies against a novel protein-glycolipid conjugate

Despite the widespread use of multidrug therapy for treatment, delays in clinical recognition and under-reporting of leprosy indicate that Mycobacterium leprae transmission is continuing. Thus, leprosy is likely to persist as a significant burden on health systems in many regions. In this study, we combined 2 previously characterized leprosy antigens, leprosy IDRI diagnostic-1 (LID-1) and ND-O, into the single fusion complex (ND-O–LID) and determined the serum antibody responses of leprosy patients from Colombia and the Philippines. Following confirmation that antibodies recognized each component within the conjugate, we assessed the performance of a rapid enzyme-linked immunosorbent assay (ELISA) system (Leprosy DetectTM fast ELISA; InBios International, Inc., Seattle, WA, USA) based on ND-O–LID capable of generating results within 1.5hours of sample addition. We found ELISA results correlated with the bacteriological index and Ridley–Jopling categorization, with lepromatous leprosy patients having the highest responses, while those of borderline tuberculoid patients were lower. Multibacillary (MB) leprosy patients were distinguished with a high degree of sensitivity (95.7%) and specificity (93.2%), suggesting that this ELISA could potentially replace invasive and insensitive skin slit smear procedures that require expert microscopic examinations. Due to the speed and robustness of this assay, we believe this is an excellent tool for detecting MB leprosy patients in a simple and highly-quantitative manner.

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/Principal FindingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/SignificanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

Tumour necrosis factor-alpha (TNF-alpha) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions.

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.

Circulating cytokine profiles in leprosy patients

Leprosy is a chronic infectious disease caused by Mycobacterium leprae which is an obligate intracellular pathogen. It is characterised by a broad spectrum of clinical forms dictated by the patient's immune response to the organism. The tuberculoid pole has good cell mediated immunity to M. leprae, with few lesions and bacilli while the lepromatous pole has poor immunity coupled with extensive involvement and greater bacillary load. We studied serum levels of interferon gamma and interleukin 6 in 100 patients of untreated leprosy, compared them with 30 age and sex matched normal healthy controls and co-related them with different parts of the spectrum and reactional episodes. The purpose of this study was to delineate the role of cytokines and their clinical implications in the leprosy spectrum and during reactional episodes. We observed that mean cytokine levels were significantly higher in the patient group as compared to the controls. In the non reactional patient group, pure neuritic leprosy patients showed highest levels of INFgamma which were directly proportional to the extent of nerve involvement. Lepromatous leprosy patients had the highest levels of IL6. Bacteriological index demonstrated a negative and positive corelation with INFgamma and IL 6 levels respectively. Type I and Type II reactional patients had higher levels of INFgamma and IL 6 respectively as compared to nonreactional patients. Our results suggest that pure neuritic leprosy and borderline tuberculoid patients in type I reaction are at greatest risk for nerve and tissue damage. Thus cytokines have the potential to play a significant role in classification, prognosis and treatment of leprosy.

Leprosy-specific B-cells within cellular infiltrates in active leprosy lesions

Leprosy is a spectral disease with polar lepromatous and tuberculoid forms correlating with enhanced humoral and cell-mediated immunity, respectively, against Mycobacterium leprae and the borderline forms, borderline lepromatous, midborderline, and borderline tuberculoid showing in-between clinical and immunological characteristics. Histopathologically, the cellular infiltrates of leprosy lesions show predominantly the presence of interacting T-cells and antigen presenting cells like macrophages, whereas the presence of B-cells has only been sporadically reported. The present study demonstrates by immunohistochemical techniques the presence of B-cells, including plasma cells, in active lesions from lepromatous leprosy, skin smear negative borderline lepromatous, and paucibacillary borderline tuberculoid leprosy. Furthermore, the study demonstrates the in situ production of M leprae-specific antibodies from BT lesions using an organotypic skin explant culture model. Finally, analysis of the cytokine release profile in supernatants of lesional organotypic skin cultures showed a microenvironment conducive to the differentiation and maturation of B-cells. The results demonstrate the presence of different functionally active B-cell stages within lesions of patients with leprosy, including borderline tuberculoid patients, which could secrete anti-M leprae-specific antibodies. However, their role in leprosy pathology remains to be elucidated.

Thalidomide does not modify the ability of cells in leprosy patients to incorporate [3H]-thymidine when incubated with M. leprae antigens

The immune response in reversal reaction, (RR) and in erythema nodosum leprosum (ENL) is characterized in vitro by an enhancement in lymphocyte blast transformation against M. leprae. As thalidomide is an effective treatment for ENL, this study assessed the effect of this drug on these phenomena. Mononuclear cells from patients attending the clinic at ALERT and from healthy staff were cultured for 5 days with integral M. leprae (IMl), or a modified Dharmendra antigen (Dhar), or PPD from M. tuberculosis. In one set of cultures, thalidomide was added once at the initiation of the culture; in the other set thalidomide was added a second time (2x), 18 h prior to harvesting the cells. The mononuclear cells, in the absence of thalidomide, from healthy staff, borderline tuberculoid patients (BT) and BT patients in RR (BT/RR) incorporated [3H]-thymidine best when cultured with PPD > Dhar > M. leprae. The cells from patients with ENL did not respond well to the M. leprae antigens. Thalidomide (2x) enhanced proliferation to Dhar in the BTRR group (Wilcoxon signed rank test, P < 0.05). No significant changes occurred for the other groups. Comparing PPD-stimulated cells treated with thalidomide once to those treated with thalidomide twice, thalidomide (2x) suppressed incorporation of [H3]-thymidine by the PPD-stimulated (P < 0.05) as well as IMl-stimulated (P < 0.05) cells in the healthy staff group. In the Dhar-stimulated cells from the healthy staff thalidomide significantly suppressed TNF-alpha (P < 0.05). A mixed effect was seen within and between the other groups, but there was a trend for thalidomide to suppress TNF-alpha induced by the M. leprae, Dhar and PPD antigens.

Urinary Phenolic Glycolipid 1 in the Diagnosis and Management of Leprosy

A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy. One hundred seventy-nine previously untreated patients and 25 normal controls were tested. The specificity of the assay was 100%. There were no false-positive results. The sensitivity of the assay varied with the type of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and 18% for borderline tuberculoid patients. After the onset of chemotherapy in lepromatous leprosy patients, there was often a transient increase of urinary PGL-1, followed by a steady decline. Within 3 months of multiple drug therapy, urinary PGL-1 levels were reduced by 90%-99% and were often undetectable. This assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with Hansen's disease.

Differential expression of Langerhans cells in the epidermis of patients with leprosy.

Eighteen patients with lepromatous leprosy (LL) showed a significant reduction (P less than 0.001) of Langerhans cells (LC) irrespective of whether the biopsies were obtained from involved (398 +/- 186) or healthy skin (304 +/- 98). The cells showed morphological changes consisting mainly of loss of dendritic processes. Twenty-four controls (age, sex and race matched) had a mean number of LC of 632 +/- 138. In tuberculoid patients (TT) significant differences were observed, depending on the site of biopsy. Nine biopsies from involved skin had 993 +/- 206 LC, whereas 11 from healthy skin had 448 +/- 96 (P less than 0.001). This difference was confirmed in six additional borderline tuberculoid (BT) and TT patients in whom biopsies were simultaneously obtained from involved (973 +/- 179) and uninvolved skin (498 +/- 99). In 10 patients with indeterminate leprosy the LC density did not differ from the control population (630 +/- 261). The expression of LC numbers in BT and TT patients may represent migration of these cells from healthy skin to involved areas or mobilization of a central pool. The low density found in LL patients could interfere with adequate presentation of mycobacterial antigens leading to tolerance. Alternatively the presence of T helper cells in TT infiltrates may produce factors that recruit LC; their absence in LL lesions may account for the decrease in LC expression.

Testicular dysfunction in leprosy: relationships of FSH, LH and testosterone to disease classification, activity and duration

Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were determined by radioimmunoassay (RIA) in leprosy patients and analysed for effect of disease classification, disease activity and duration of disease. LH and FSH levels were found to be significantly elevated in lepromatous patients compared to borderline-lepromatous, midborderline and borderline-tuberculoid patients. A positive correlation was seen between LH and FSH and a negative correlation was seen between testosterone and both LH and FSH. No correlation was seen between hormone levels and measures of disease activity: bacillary index and IgM to phenolic glycolipid I, a Mycobacterium leprae antigen. A significant correlation was seen between duration of disease and FSH when age was taken into account, indicating that testicular dysfunction is probably cumulative and irreversible. It is recommended that LL patients be routinely screened for hypogonadism using FSH, LH and testosterone levels.

Serodiagnosis of leprosy: relationships between antibodies to Mycobacterium leprae phenolic glycolipid I and protein antigens.

Sera from leprosy patients and controls were assayed for immunoglobulin M (IgM) and IgG antibodies to the Mycobacterium leprae-specific phenolic glycolipid I antigen (PG) by enzyme-linked immunosorbent assay, for IgG antibodies to M. leprae protein antigens by Western immunoblot, and for antibodies to a 65-kilodalton (kDa) protein antigen of M. leprae by a competition antibody binding assay. Elevated levels of anti-PG IgM were seen in lepromatous and borderline lepromatous patients, and elevated levels of anti-PG IgG were seen in borderline lepromatous patients. There was a significant correlation between the bacillary index (BI) and anti-PG IgM whether all leprosy patients or only multibacillary patients were analyzed. A significant correlation was seen between anti-PG IgG and BI when all leprosy patients were used for analysis, but not when only multibacillary patients were used. IgG antibodies to protein antigens of M. leprae, as detected by Western immunoblot, were more prevalent in lepromatous and borderline lepromatous patients than in borderline tuberculoid patients, while one of eight controls showed one weak band. There were significant correlations between the number of M. leprae protein antigens detected by the sera of patients and both BI and the level of anti-PG IgM. The 65-kDa competition antibody binding assay detected active multibacillary leprosy. Patients positive for antibody to the 65-kDa antigen had a significantly higher BI and levels of anti-PG IgM and anti-PG IgG than did patients that were negative. In addition, the level of antibody to the 65-kDa antigen correlated with both the BI and anti-PG IgM. We conclude that testing for antibodies to protein antigens of M. leprae may provide a useful adjunct to testing for antibodies to PG.

Demonstration of mycobacterial antigens in nerve biopsies from leprosy patients using peroxidase-antiperoxidase immunoenzyme technique

Peripheral nerve biopsies from patients with leprosy were stained with anti- Mycobacterium bovis (BCG) in a peroxidase-antiperoxidase (PAP) system to demonstrate intraneural mycobacterial antigens. Most M. leprae antigens have been shown to crossreact with BCG. Of the 30 biopsies from borderline tuberculoid (BT) patients 18 had acid-fast bacilli while 26 of them had demonstrable mycobacterial antigens in their nerves. All borderline lepromatous (BL) and lepromatous leprosy (LL) nerve biopsies had both M. leprae and mycobacterial antigens within them. Most of the antigens in the BT patients were seen to be extracellular. In BL and LL patients antigens were seen both extracellularly and intracellularly in Schwann cells and infiltrating macrophages. Mycobacterial antigens in BT nerves were always seen to be surrounded by a mononuclear cell reaction while in the BL and LL patients antigens could be seen with minimal cellular infiltrate and the neural architecture was more or less preserved. While bacilli could not be seen in BT patients who had been released from treatment for more than 4 years, mycobacterial antigens could still be seen in some patients who had been released from treatment for up to 5 years. Patients with no skin lesions but with large, painful, or tender nerves were found to have intraneural inflammation surrounding mycobacterial atigens, while those with a similar clinical picture but without tender or painful nerves showed no marked inflammation within their nerves despite the presence of mycobacterial antigens. From these findings it was concluded that immunologically mediated inflammatory response toward intraneurally located M. leprae antigens in conjunction with other host factors may be necessary for nerve damage in the BT leprosy patients. In the BL and LL patients the mechanisms of nerve damage are still unknown with certainty but local effects and immune-complex damage secondary to abundant M. leprae antigens are worth exploring. The use of immunohistological techniques should offer a new approach in the study of the immunopathology of leprosy.

Defective gamma interferon production in leprosy. Reversal with antigen and interleukin 2.

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.

Serum trace elements and vitamin A in leprosy subtypes

Serum zinc, copper, iron, and vitamin A levels were determined in patients with leprosy and healthy controls. Leprosy patients were classified according to the Ridley and Jopling classification and divided into two main groups as follows: tuberculoid, which consisted mainly of borderline tuberculoid patients and lepromatous, which consisted of borderline lepromatous and true lepromatous patients. The lepromatous group was found to have significantly lower serum levels of zinc and iron and elevated levels of copper. Vitamin A levels were also significantly lower in the lepromatous groups than in the tuberculoid group. Furthermore, the true lepromatous vitamin A determinations were significantly lower than those of the borderline lepromatous patients. The mechanism of these alterations in trace elements is probably due to a redistribution of these metals from the blood to various tissues; brought about by the release of leucocyte endogenous mediators by continuing phagocytosis of tissue macrophages in the lepromatous group of patients.

Circulating antibodies to connective tissue microfibrils and dermal immunoglobulin deposits in leprosy

Subepidermal fibrillar deposits containing IgM immunoglobulin occur in apparently normal skin from leprosy patients. The distribution of the deposits is similar to that of the microfibrillar epidermis anchoring system which consists of elastic fibers. The deposits may be related to the presence of a novel autoantibody reacting with connective tissue microfibrils and the microfibrillar part of elastic fibers. The antibodies were of IgM class and were found in 67 of 97 leprosy patients. They occurred in higher titer in patients classified as borderline lepromatous as compared to borderline tuberculoid patients.