Pathogenesis of Leprosy: An Insight Into B Lymphocytes and Plasma Cells.

The pathogenesis of leprosy is still not fully understood. Several studies have been performed on the involvement of T cells in leprosy and more recently have focused on genetic factors and innate immune response. There are still only few reports about the role of B cells in active leprosy lesions in different spectral forms of the disease. The literature on tuberculosis suggests that B cells play an important role in the regulation of the granulomas, in cytokine production, T-cell response, and antigen presentation. Only few studies investigated the role of B cell in leprosy. We investigated the distribution of B cells in 85 leprosy biopsies covering all forms of the disease and compared results with 13 biopsies of tuberculosis and atypical mycobacteriosis, expanding the previous experiences. A statistically significant difference in the number of CD20 (P = 0.014) and CD138+ (P = 0.01) cells between the different forms of leprosy was observed. A remarkable amount of CD138+ cells could also be detected in borderline tuberculoid. The median of the CD20 cells decreased from the bacilloscopy-negative samples to the bacilloscopy-positive samples by 50% (P = 0.004). Contrarily, the median of CD138+ cells showed an increase from bacilloscopy-negative to bacilloscopy-positive samples of 966.67% (P = 0.001). In our experience, tuberculoid leprosy showed more B cells and less plasma cells than lepromatous leprosy. Our results show that B cells might be implicated in leprosy pathogenesis, not only in the lepromatous pole as previously postulated, but also in tuberculoid granuloma formation and type 1 reactions.

Leprosy and Lobomycosis: First report from the Amazon Region.

Leprosy is still a relevant health problem in Brazil with 31 044 new cases diagnosed in 2013, of which 781 new cases diagnosed in the State of Amazonas. Lobomycosis is a cutaneous-subcutaneous mycosis caused by Lacazia loboi, an in vitro uncultivable fungus. Lobomycosis has been mainly reported in the Amazon region of Brazil and Colombia affecting mainly male farmers and workers in extraction of rubber. Lobomycosis is clinically characterised by keloid-like lesions and chronic evolution. Even if lobomycosis does not represent a major public health problem, it remains a serious condition for patients due to unsatisfactory treatment. We report a case of an old man with lepromatous leprosy diagnosed in 1983, treated with multidrug therapy until 1989 and presenting a leprosy relapse 15 years after treatment. At this time a lobomycosis was also diagnosed in a keloid-like lesion evolving for more than 30 years. This co-infection has been only rarely reported and this is the first detailed case report in the English literature.

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states.

BACKGROUND: Leprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies. OBJECTIVES: This study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy. METHODS: We performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients]. RESULTS: FoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344). CONCLUSIONS: These findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction.

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states

BACKGROUND: Leprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies. OBJECTIVES: This study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy. METHODS: We performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients]. RESULTS: FoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344). CONCLUSIONS: These findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction. .

Histopathology of the lepromatous skin biopsy.

The histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against Mycobacterium leprae. In tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (AFB) are absent or only rarely present. In borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. AFB are numerous. Edema inside and outside the epithelioid granulomas, together with the appearance of large giant cells, are the main features of type 1 reactions. A conspicuous neutrophilic infiltrate in the subcutis with or without vasculitis is found in erythema nodosum leprosum. The main histopathologic features of leprosy and its particular forms are discussed in this review.

Histopathology of the lepromatous skin biopsy

The histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against Mycobacterium leprae. In tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (AFB) are absent or only rarely present. In borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. AFB are numerous. Edema inside and outside the epithelioid granulomas, together with the appearance of large giant cells, are the main features of type 1 reactions. A conspicuous neutrophilic infiltrate in the subcutis with or without vasculitis is found in erythema nodosum leprosum. The main histopathologic features of leprosy and its particular forms are discussed in this review.

Leprosy and HIV coinfection: a critical approach.

An increase in leprosy among HIV patients, similar to that observed in patients with TB, was expected approximately 20 years ago. Studies conducted in the 1990s together with those reported recently seemed to indicate that a coinfection with HIV did not alter the incidence and the clinical spectrum of leprosy and that each disease progressed as a single infection. By contrast, in countries with a high seroprevalence of HIV, TB was noted to increase. Explanations may be provided by the differences in the incubation time, the biology and toxicity of Mycobacterium leprae and Mycobacterium tuberculosis. After the introduction of HAART the leprosy-HIV coinfection manifested itself as an immune reconstitution inflammatory syndrome (IRIS), typically as paucibacillary leprosy with type 1 leprosy reaction. The incidence of leprosy in HIV-infected patients has never been properly investigated. IRIS-leprosy is probably underestimated and recent data showed that the incidence of leprosy in HIV patients under HAART was higher than previously thought.

New insights in the pathogenesis and genetics of leprosy.

In the last 30 years the leprosy burden has been dramatically reduced but over the last 5 years still more than 200,000 new cases were detected each year. Advances in immunology, pathogenesis, and genetics of leprosy have been reported. A deeper understanding of the mechanisms of infection will ultimately improve our ability to fight against this potentially devastating infectious disease.

Leprosy and HIV coinfection: a clinical, pathological, immunological, and therapeutic study of a cohort from a Brazilian referral center for infectious diseases.

BACKGROUND: Although awareness of the relevance of leprosy and human immunodeficiency virus (HIV) coinfection is increasing worldwide, several aspects of this co-occurrence are not fully understood. METHODS: We describe clinical, pathological, immunological, and therapeutic long-term follow-up of a cohort of 25 individuals with leprosy and HIV infection from Manaus, Amazonas. RESULTS: Careful description of our cohort indicates a higher prevalence of leprosy in an HIV-positive population than that in the general population. We also observed upgrading shifting of leprosy clinical forms after initiation of highly active antiretroviral therapy and multidrug therapy and an impact of HIV infection on leprosy granuloma formation, among other features. CONCLUSION: Taken together, these new insights allow the proposition of a classification system that includes (1) leprosy and HIV true coinfection, (2) opportunistic leprosy disease, and (3) leprosy related to highly active antiretroviral therapy.

T regulatory cells and plasmocytoid dentritic cells in hansen disease: a new insight into pathogenesis?

Leprosy is characterized by spectrum of histologically different granulomatous skin lesions that reflects the patient's immune response to Mycobacterium leprae. Presence, frequency, and distribution of both CD4+ CD25+ FoxP3+ T regulatory cells (T-regs) and CD123+ plasmacytoid dendritic cells in leprosy have never been investigated. We performed a retrospective immunohistochemical study on 20 cases of leprosy [tuberculoid tuberculoid (TT): 1 patient; borderline tuberculoid (BT): 3 patients; borderline lepromatous (BL): 5 patients; lepromatous lepromatous (LL): 5 patients; borderline borderline in reversal reaction (BB-RR): 1 patient; BT-RR: 2 patients; and erythema nodosum leprosum (ENL): 3 patients]. FoxP3-positive cells were present in 95% of the cases with an average density of 2.9% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was no statistical difference of FoxP3 expression between TT, BT, BL, and LL, whereas a statistical significant increment (P = 0.042) was observed in patients affected by reversal leprosy reactions (BT-RR and BB-RR) compared with patients affected by ENL and patients with nonreactional disease forms (BL, LL, BT, TT). CD123 expression was not observed in any of the biopsy specimens evaluated; with the exception of 2 cases of ENL, in which a focal positivity for CD123 was observed. Our results show that plasmacytoid dendritic cells are not involved in the immune response against M. leprae while T-regs are present in leprosy skin lesions. These data raise the question if T-regs have a pathogenetic role in HD as previously demonstrated in Leishmania major and Mycobacterium tuberculosis.