Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-ß, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Clinical analysis of 20 cases of cutaneous extranodal NK/T-Cell lymphoma.

Background To investigate the clinical features, pathological features and prognostic factors of cutaneous extranodal natural killer/T-cell lymphoma (CENKTL). Methods A total of 20 cases with CENKTL from February 2013 to November 2021 were analysed retrospectively. Results The patients included 15 men and five women, and their ages ranged from 19 to 92 (median age of 61) years. The most common lesions were on the extremities, followed by the trunk. Histopathological examination showed atypical lymphocyte infiltrate in dermis and subcutaneous fat. The tumour tissue showed vascular proliferation, vascular occlusion, and coagulation necrosis. In situ hybridisation revealed that 20 patients were positive for Epstein-Barr virus-coding ribonucleic acid. Immunohistochemistry showed that the tumour cells were positive for CD3 (18/20 and 90%), CD56 (19/20 and 95%), T-cell intracellular antigen (TIA-1) (13/14 and 92.9%) and CD20 (5/20, 25%). About 20 patients were positive for Ki-67 with values of 30-90%. A total of 11 of the 20 patients died, and two patients were lost to follow-up. The 2-year overall survival was 24%, and the median overall survival was 17 months. Univariate analysis revealed that involvement of lymph nodes (P = 0.042) correlated with worse survival. Limitation This is a retrospective study design and has a limited number of patients. Conclusion CENKTL is rare and has a poor prognosis. Diagnosis is challenging due to non-specific clinical symptoms and histopathology results. A comprehensive judgement should be made based on related clinical manifestations and histopathological and molecular examination. Lymph node involvement is an independent prognostic factor for CENKTL.

Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases.

BACKGROUND: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. AIMS: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. MATERIALS AND METHODS: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. RESULTS: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. LIMITATIONS: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. CONCLUSION: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

Skin fibrosis associated with keloid, scleroderma and Jorge Lobo's disease (lacaziosis): An immuno-histochemical study.

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-ß. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-ß was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.

Mycobacterium leprae on Palatine Tonsils and Adenoids of Asymptomatic Patients, Brazil.

We investigated palatine tonsil and adenoid specimens excised from otorhinolaryngological patients in a leprosy-endemic region of Brazil. Fite-Faraco staining identified Mycobacterium spp. in 9 of 397 specimen blocks. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium leprae, indicating that these organs can house M. leprae in persons inhabiting a leprosy-endemic region.

Ocular erythema nodosum leprosum: An immunohistochemical study.

Episcleritis, scleritis, and anterior uveitis are common clinical manifestations of ocular leprosy. Erythema nodosum leprosum (ENL) is an acute, exaggerated systemic immunological reaction that complicates the course of this chronic indolent disease. We present an ocular immunohistochemical study of severe form of ENL involving even the ciliary body and choroid resulting in the perforation of the globe on the initiation of anti leprosy therapy. We used CD-3, CD-68, S-100, and CD-20 for immunohistochemistry. It revealed plenty of CD-3-positive T-cells and CD-68-positive macrophages and a few S-100 and CD-20-positive cells. The inflammatory exudates stained positive for IgG and IgM. The diagnosis was ocular ENL.

Expression of CD117 and platelet-derived growth factor receptor α in patients with alopecia areata.

BACKGROUND: Alopecia areata is a disease of uncertain, probably autoimmune etiology. The role of growth factors like platelet-derived growth factor and C-kit (CD117) in alopecia areata is unknown. AIMS: To compare the expression of CD117 and platelet-derived growth factor receptor α in tissue samples of alopecia areata and normal controls. METHODS: Thirty biopsy samples of alopecia areata and eighteen normal control samples were included in this cross-sectional study. Immunohistochemistry was done to detect the expression of CD117 and platelet-derived growth factor receptor α in cases and controls. The mean percentage of follicles expressing CD117 and platelet-derived growth factor receptor α was compared among cases and controls. RESULTS: The mean number of follicles expressing CD117 in anagen and catagen hairs differed significantly among cases and controls. The extent and intensity of staining with platelet-derived growth factor receptor α correlated significantly with the severity of alopecia areata based on the severity of alopecia tool score. LIMITATIONS: Confirmation of the expression pattern of molecules observed in immunohistochemistry with western blot or polymerase chain reaction would have strengthened the report. CONCLUSIONS: The expression of CD117 varied in cases and controls. The expression of platelet-derived growth factor receptor α correlated with the severity of the disease. This could explain how platelet-rich plasma works in the treatment of alopecia areata. Further studies are required to explore the role of these molecules in autoimmune pathogenesis.

Second to fourth digit ratio in female patients with acne vulgaris: Could it be a predictor of androgen receptor status?

BACKGROUND: Second to fourth digit (2D:4D) ratio is the ratio of index to ring fingers length. It reflects prenatal androgen exposure and sensitivity. Androgens are important in the pathogenesis of acne vulgaris, This ratio may therefore be of significance in determining the expression of androgen receptors. AIM: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris. METHODS: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method. RESULTS: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = -0.28;P = 0.02), hair follicles (r = -0.22; P = 0.05) and fibroblasts (r= -0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = -0.397; P < 0.000) only. LIMITATIONS: Lack of follow-up and absence of male participants were the main limitations of this study. CONCLUSION: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors. Taken together, second to fourth digit ratio could help in designing plans for treatment of acne vulgaris.

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions.

BACKGROUND: Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. METHODS: We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. RESULTS: The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. CONCLUSION: M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.

Langerin (CD207)-positive cells in leprosy: Possible implications for pathogenesis of the disease with special emphasis on dermal immunoreactivity.

Leprosy is a disease caused by Mycobacterium leprae, which is characterized by two distinct poles, the tuberculoid pole and the lepromatous pole, depending on the immune response to the bacillus. Langerin-positive cells are dendritic cells that appear to play an essential role in the development of the disease. These cells are specialized in the processing and presentation of antigens, exerting an important function in the activation of the immune system. To evaluate the expression of langerin-positive cells (CD207+) in skin lesion fragments of patients with a diagnosis of M. leprae infection and to associate the expression of these cells with the polar forms of the disease. Langerin-positive cells were detected in larger numbers in lesions of patients with the tuberculoid form compared to those with the lepromatous form. The presence of a larger number of these cells in patients with the tuberculoid form suggests an important participation of langerin-positive cells, capturing antigens and favoring an effective immune response to infection with M. leprae.

Reduced immunohistochemical expression of CCN3 in vitiligo.

BACKGROUND: Defective adhesion seems to be involved in the chronic loss of melanocytes observed in vitiligo. Recent findings showed an association of genetic variants of an adhesion gene with vitiligo and reduced immunohistochemical expression of some adhesion molecules in vitiligo skin. AIMS: To compare CCN3 immunohistochemical expression in lesional and non-lesional epidermis of individuals with vitiligo. METHODS: A total of 66 skin specimens from 33 volunteers with vitiligo were analyzed by immunohistochemistry using anti-CCN3 antibodies. Absence of topical or systemic treatment for vitiligo over the previous 30 days and availability of an area of non-lesional skin for biopsy at least 15 cm away from any vitiliginous macules were the main inclusion criteria. RESULTS: A significant reduction of CCN3 expression was observed in lesional skin as compared to non-lesional skin (P = 0.001). LIMITATIONS: Paraffin embedded skin samples do not allow investigation by molecular biology methods. Not all samples allowed analysis due to the lamina preparation technique. Complete clinical data was not available for all patients. CONCLUSION: Our results support the hypothesis of impaired cell adhesion in vitiligo suggested by genetic studies. The pattern of immunohistochemical expression suggests that vitiligo might be an epithelial disease and not just a melanocyte disorder.

Clear cell odontogenic carcinoma. A review.

INTRODUCTION: Clear cell odontogenic carcinoma (CCOC) is described as an exceptional and hard to diagnose malignant tumor which was first reported by Hansen in 1985. The purpose of this review article is to show that CCOC is a not that rare entity and to discuss its various aspects in order to enhance the diagnosis. MATERIAL AND METHODS: A search in the English language literature was performed using the Scopus, ScienceDirect, PubMed and Medline databases between 1985 and 2016. Data were collected on epidemiologic, clinical, radiographic, histological, immunohistochemistrical, cytogenetic, management, follow-up and prognosis features of CCOC. RESULTS: Sixty-five studies from which a total of 95 case reports were included in the review. CCOC was generally seen in the fifth decade and the most common site was mandibular. The most frequently found symptoms were swelling, tooth mobility and pain. Radiologically, the image was radiolucent and could look like a cyst or a periodontal lesion. In situ hybridization techniques frequently expressed a gene fission of EWSR1. The treatment was mostly a radical surgical excision of the tumor with or without adjuvant radiotherapy or chemotherapy. CCOC showed high rates of recurrence and mortality related with the presence of distance metastasis. DISCUSSION: Fission of EWSR1 gene could be the main element it the diagnosis of CCOC. A multidisciplinary approach, including a radiologist, pathologist and an oral & maxillofacial surgeon may be helpful in the evaluation and management of these lesions. With 95 reports found in English literature, we cannot say that CCOC is extremely rare anymore.

Clear cell odontogenic carcinoma, diagnostic difficulties. A case report.

INTRODUCTION: Clear cell odontogenic carcinoma (COCC) is a rare tumor described by Hansen et al. in 1985. The clinical and radiological manifestations are multiple and the diagnosis is histological. OBSERVATION: A 64-year-old patient consulted us for a right mandibular osteolytic lesion associated to a homolateral labial hypoesthesia. A biopsy was performed under local anesthesia. Histology was consistent with a metastatic lesion of clear kidney cell carcinoma, COCC, or odontogenic squamous tumor. Additional tests eliminated a metastatic lesion. A wide excision of the lesion by hemi-mandibulectomy associated with lymph node dissection and reconstruction by a fibula osteoseptocutaneous flap was performed. Presence of a fission of the EWSR1 gene on the histological examination of the surgical specimen made the diagnosis of COCC. DISCUSSION: Our observation illustrates the difficulty of diagnosing COCC. The new contribution of the cytogenetic techniques such as FISH-type techniques makes possible the improvement of the diagnosis.

The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions.

Jorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus.

Th9 cytokines response and its possible implications in the immunopathogenesis of leprosy.

AIMS: Leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, LL) to tuberculoid leprosy (resistance, TT). The immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. Classically, the clinical evolution of leprosy has been associated with Th1/Th2 cytokine profiles, but the role of new cytokine profiles such as T helper 9 (Th9) remains to be elucidated. METHODS: To evaluate the tissue expression profile of these cytokines, a cross-sectional study was conducted using a sample of 30 leprosy skin lesion biopsies obtained from patients with leprosy, 16 TT and 14 lepromatous LL. RESULTS: Immunohistochemical analysis revealed a significant difference in interleukin (IL)-9, IL-4 transforming growth factor (TGF)-ß and IL-10 levels between the two groups. IL-9 was more expressed in TT lesions compared with LL lesions. Higher expression of IL-4, IL-10 and TGF-ß was observed in LL compared with TT. IL-4, IL-10 and TGF-ß tended to be negatively correlated with the expression of IL-9, indicating a possible antagonistic activity in tissue. CONCLUSIONS: The results suggest that Th9 lymphocytes may be involved in the response to Mycobacterium leprae, positively or negatively regulating microbicidal activity of the local immune system in the disease.

Genome-Wide Screening of mRNA Expression in Leprosy Patients.

Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified 1580 differentially expressed mRNAs [Fold Change (FC) ≥ 2.0, p ≤ 0.05] in diseased lesions vs. healthy controls. Some of these genes were observed in all forms of the disease (CD2, CD27, chit1, FA2H, FAM26F, GZMB, MMP9, SLAMF7, UBD) and others were exclusive to reactional forms (Type "1" reaction: GPNMB, IL1B, MICAL2, FOXQ1; Type "2" reaction: AKR1B10, FAM180B, FOXQ1, NNMT, NR1D1, PTX3, TNFRSF25). In literature, these mRNAs have been associated with numerous pathophysiological processes and signaling pathways and are present in a large number of diseases. The role of these mRNAs maybe studied in the context of developing new diagnostic markers and therapeutic targets for leprosy.

Genome-wide screening of mRNA expression in leprosy patients

Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified 1580 differentially expressed mRNAs [Fold Change (FC) ≥ 2.0, p ≤ 0.05] in diseased lesions vs. healthy controls. Some of these genes were observed in all forms of the disease (CD2, CD27, chit1, FA2H, FAM26F, GZMB, MMP9, SLAMF7, UBD) and others were exclusive to reactional forms (Type "1" reaction: GPNMB, IL1B, MICAL2, FOXQ1; Type "2" reaction: AKR1B10, FAM180B, FOXQ1, NNMT, NR1D1, PTX3, TNFRSF25). In literature, these mRNAs have been associated with numerous pathophysiological processes and signaling pathways and are present in a large number of diseases. The role of these mRNAs maybe studied in the context of developing new diagnostic markers and therapeutic targets for leprosy.

Relationship between growth factors and its implication in the pathogenesis of leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae which affects the skin and peripheral nervous system. The immune response of the host determines the clinical course of the disease. The tuberculoid form is the result of high cell-mediated immunity characterized by a Th1 response, whereas the lepromatous form is characterized by low cell-mediated immunity and a Th2 humoral response. The neural damage established produces marked changes in the expression of growth factors such as nerve growth factor (NGF) and its receptors (NGF-R). The expression of NGF, associated with the expression of Th1 and Th2 cytokines, might be involved in the tissue damage caused by the bacillus. Therefore, the objective of this study was to correlate the immunoexpression patterns of NGF and NGF-R in the different clinical forms of leprosy, and to associate the findings with the in situ expression of TGF-ß and clinical classification of the disease. TGF-ß, NGF and NGF-R immunoexpression was analyzed by immunohistochemistry in paraffin-embedded material. Most patients were males with a mean age of 40.7 years. TGF-ß levels were significantly higher in the lepromatous forms. No significant difference in the immunoexpression of NGF or NGF-R was observed between the clinical forms, but expression tended to be higher at the lepromatous pole. There was a significant positive correlation between NGF and NGF-R in the different clinical forms of leprosy. A significant positive correlation was observed between NGF, NGF-R and TGF-ß. It can be concluded that, even existing evidence on the role of these molecules in the clinical spectrum of leprosy.

Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.

In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.