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Jane Tomimori - One of the best experts on this subject based on the ideXlab platform.
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human leukocyte antigen class i and class ii alleles are associated with susceptibility and resistance in Borderline Leprosy patients from southeast brazil
BMC Infectious Diseases, 2015Co-Authors: Fabiana Covolo De Souzasantana, Maria Esther Salles Nogueira, Elaine Valim Camarinha Marcos, Somei Ura, Jane TomimoriAbstract:Evidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and Borderline (B) Leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B Leprosy including Borderline-tuberculoid (BT), Borderline-Borderline (BB), and Borderline-lepromatous (BL). DNA was obtained by the salting-out technique from the blood samples of 202 patients with B Leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers. The case-controlled analysis results showed a significant association between B Leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20–0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3–0.8, pc = 0.039). A protective association was observed between BL Leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15–0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30–5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease. The results indicate the involvement of HLA class I and class II molecules in B Leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.
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Leprosy Reversal Reaction as Immune Reconstitution Inflammatory Syndrome in Patients with AIDS
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2008Co-Authors: Mariana Dias Batista, Adriana Maria Porro, Solange M. Maeda, Elimar Elias Gomes, Márcia C. N. Yoshioka, Milvia Maria Simões E Silva Enokihara, Jane TomimoriAbstract:We report 2 instances in which reactional Borderline Leprosy manifested itself as an immune reconstitution phenomenon in patients with acquired immunodeficiency syndrome. We discuss the clinical, laboratory-based, histopathologic, and immunohistochemical characteristics of both patients. Furthermore, we review similar reports from the literature.
Raj Kamal - One of the best experts on this subject based on the ideXlab platform.
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histopathological upgrading using mycobacterium indicus pranii mip vaccine as an immunotherapeutic with standard chemotherapy in Borderline Leprosy a double blind randomized placebo control trial
Journal of Immunology and Immunotherapy, 2019Co-Authors: Raj Kamal, M Natrajan, Vinay Kumar Pathak, Alpana KumariAbstract:Immunotherapy with BCG, BCG+ M. leprae, ICRC, MIP has been observed to be effective in improving the treatment in Leprosy. Histopathological upgrading using MIP vaccine has been reported in cases with the high bacillary load. However, very little information is available in Borderline Leprosy which is characterized by a state of shifting immunity and would, therefore, be ideally suited to such observations. This study is originated from the involvement of our Institute in trials aimed at improving the therapy of Leprosy by using combined immunotherapy and chemotherapy.
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addition of mycobacterium indicus pranii vaccine as an immunotherapeutic to standard chemotherapy in Borderline Leprosy a double blind study to assess clinical improvement preliminary report
British Journal of Dermatology, 2017Co-Authors: Raj Kamal, M Natrajan, K Katoch, Vinay Kumar Pathak, Alpana Kumari, H K KarAbstract:The response of Leprosy patients to chemotherapy (WHO-Multi Drug Therapy) though generally good and predictable, exhibits variations in a section of cases. Some cases show a dramatic response while others show a slower response such variations are a reflection of the immune status of the host. This article is protected by copyright. All rights reserved.
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addition of immunotherapy to chemotherapy in pediatric Borderline Leprosy a clinical evaluation
International Journal of Contemporary Pediatrics, 2016Co-Authors: Raj Kamal, M Natrajan, R DayalAbstract:Background: Immunotherapy with BCG, BCG + M. leprae, ICRC, MIP has been observed to be effective in improving the treatment in adulthood Leprosy. Clinical improvement with accelerated bacterial clearance and histological up grading using MIP vaccine as an immunotherapeutic with standard WHO-MDT has been reported in adult cases with high bacillary load. However, there is lack of information in Borderline pediatric Leprosy which is characterized by a state of shifting immunity and would therefore be ideally suited to such observations. This pilot study is originated from involvement of our Institute in a trial aimed for improving the therapy of pediatric Borderline Leprosy by using combined immunotherapy and chemotherapy. The study was aimed to assess the clinical improvement by adding immunotherapy (MIP vaccine) with chemotherapy (WHO -MDT) in pediatric Borderline Leprosy. Methods: A total of 98 new pediatric Borderline Leprosy cases were included, after formal written consent, detailed clinical examination. A non-randomized trial was conducted. In this study, patients attending the OPD were serially recruited in two treatment groups. In group-1 (Mw vaccine plus WHO- MDT) 50 pediatric cases and in Group-2 (MDT only), 48 pediatric Borderline cases were recruited. The therapeutic regimens containing MIP vaccine was injected intra-dermally at the start of therapy and every six months in addition to chemotherapy (WHO- MDT) in group 1 pediatric patient and chemotherapy only (WHO- MDT) were given in group-2 pediatric cases and effect was observed on clinical parameters (size of lesions, erythema, infiltration, sensory improvement) and bacillary clearance. Results: Addition of immunotherapy resulted in faster clinical recovery from disease, faster bacillary clearance in pediatric Borderline Leprosy cases. Conclusions: This study shows the usefulness of adding immunotherapy (MIP vaccine) to chemotherapy (WHO- MDT) in pediatric Borderline Leprosy for faster clinical improvement.
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clinical and histopathological evaluation of the effect of addition of immunotherapy with mw vaccine to standard chemotherapy in Borderline Leprosy
Indian journal of leprosy, 2012Co-Authors: Raj Kamal, M Natrajan, K Katoch, Mamta AroraAbstract:This study reports detailed analysis of clinical parameters and clearance of granuloma in Borderline Leprosy patients treated with immunotherapy and chemotherapy. It aims to assess the additive effect of immunotherapy (Mwvaccine) with standard MDT on clinical status of untreated Borderline Leprosy cases and on granuloma fraction of untreated Borderline Leprosy cases. Patients attending the OPD were serially recruited in two groups. A total of 150 cases in one treatment (trial) group (Mw vaccine plus MDT) and 120 cases in another treatment (control) group (MDT only) of border line Leprosy have been included. After the formal written consent, detailed clinical examination, charting, smear examination of all untreated Borderline patients of both groups was done, biopsies were taken from the active lesions of all patients of both groups at start of therapy and every six month thereafter till the completion of therapy. The same procedure was repeated every six months during the follow-up period. Standard MDT was given to all the patients of both groups according to type of disease. Mw vaccine 0.1 ml (0.5 x 10(9) bacilli) was injected intra-dermally at the start of therapy and every six months in addition to chemotherapy to the treatment group. The BT cases were followed up after 6 doses of MDT and 2 doses of Mw vaccine, and, the BB, BL cases were followed up after 24 doses of MDT plus 5 doses of Mw vaccine. Clinically, greater and faster improvement was observed in all the clinical parameters, faster attainment of smear negativity and two episodes of lepra reaction occurred in cases treated with combined chemotherapy and immunotherapy, as compared to controls (chemotherapy alone) wherein clinical improvement was slower in all parameters, slower attainment of smear negativity in bacillary index and seven showed the occurrence of reactions, histipathologically in addition to more rapid clearance of granuloma in immunotherapy treated group, a significant finding was an increase in the epithelioid cells population in this group. This suggests a possible immunoactivation of the macrophages especially in BB/BL immunotherapy group. Overall comparison of regression induced by chemotherapy alone with that induced by combined chemotherapy and immunotherapy shows a greater reduction in clinical parameters as well as granuloma fraction in BT cases as well as in BB/BL cases. This trial shows the potential usefulness of this approach of addition of immunotherapy to standard chemotherapy in Borderline Leprosy cases which leads to in faster recovery from disease reduced chances of reactions and faster granuloma clearance. Such information is expected to be useful in improving the immunotherapeutic approaches for treatinggranulomatous conditions in general and in Leprosy in particular.
Gil Benard - One of the best experts on this subject based on the ideXlab platform.
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A case report of erythroderma in a patient with Borderline Leprosy on reversal reaction: a result of the exacerbated reaction?
BMC Dermatology, 2017Co-Authors: Denis Miyashiro, Ana Paula Vieira, Maria Angela Bianconcini Trindade, João Avancini, José Antonio Sanches, Gil BenardAbstract:Background Erythroderma is characterized by erythema and scaling affecting more than 90% of the body surface area. Inflammatory, neoplastic and, more rarely, infectious diseases may culminate with erythroderma. Diagnosis of the underlying disorder is therefore crucial to institute the appropriate therapy. Leprosy is a chronic infectious disease that is endemic in Brazil. Here we present an unusual case of Leprosy and reversal reaction causing erythroderma, and we discuss the underlying immunological mechanisms which could contribute to the generalized skin inflammation. Case presentation We report a case of a patient with reversal reaction (RR) in Borderline Borderline Leprosy presenting with erythroderma and neural disabilities. Histopathology of the skin showed regular acanthosis and spongiosis in the epidermis and, in the dermis, compact epithelioid granulomas as well as grouped and isolated bacilli. This duality probably reflects the transition from an anergic/multibacillary state to a state of more effective immunity and bacillary control, typical of RR. Leprosy was successfully treated with WHO’s multidrug therapy, plus prednisone for controlling the RR; the erythroderma resolved in parallel with this treatment. Immunologic studies showed in situ predominance of IFNγ + over IL-4+ lymphocytes and of IL-17+ over Foxp3+ lymphocytes, suggesting an exacerbated Th-1/Th-17 immunoreactivity and poor Th-2 and regulatory T-cell responses. Circulating Tregs were also diminished. We hypothesize that the flare-up of anti-mycobacteria immunoreactivity that underlies RR may have triggered the intense inflammatory skin lesions that culminated with erythroderma. Conclusions This case report highlights the importance of thorough clinical examination of erythrodermic patients in search for its etiology and suggests that an intense and probably uncontrolled Leprosy RR can culminate in the development of erythroderma.
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a case report of erythroderma in a patient with Borderline Leprosy on reversal reaction a result of the exacerbated reaction
BMC Dermatology, 2017Co-Authors: Denis Miyashiro, Ana Paula Vieira, Maria Angela Bianconcini Trindade, João Avancini, José Antonio Sanches, Gil BenardAbstract:Erythroderma is characterized by erythema and scaling affecting more than 90% of the body surface area. Inflammatory, neoplastic and, more rarely, infectious diseases may culminate with erythroderma. Diagnosis of the underlying disorder is therefore crucial to institute the appropriate therapy. Leprosy is a chronic infectious disease that is endemic in Brazil. Here we present an unusual case of Leprosy and reversal reaction causing erythroderma, and we discuss the underlying immunological mechanisms which could contribute to the generalized skin inflammation. We report a case of a patient with reversal reaction (RR) in Borderline Borderline Leprosy presenting with erythroderma and neural disabilities. Histopathology of the skin showed regular acanthosis and spongiosis in the epidermis and, in the dermis, compact epithelioid granulomas as well as grouped and isolated bacilli. This duality probably reflects the transition from an anergic/multibacillary state to a state of more effective immunity and bacillary control, typical of RR. Leprosy was successfully treated with WHO’s multidrug therapy, plus prednisone for controlling the RR; the erythroderma resolved in parallel with this treatment. Immunologic studies showed in situ predominance of IFNγ + over IL-4+ lymphocytes and of IL-17+ over Foxp3+ lymphocytes, suggesting an exacerbated Th-1/Th-17 immunoreactivity and poor Th-2 and regulatory T-cell responses. Circulating Tregs were also diminished. We hypothesize that the flare-up of anti-mycobacteria immunoreactivity that underlies RR may have triggered the intense inflammatory skin lesions that culminated with erythroderma. This case report highlights the importance of thorough clinical examination of erythrodermic patients in search for its etiology and suggests that an intense and probably uncontrolled Leprosy RR can culminate in the development of erythroderma.
Euzenir Nunes Sarno - One of the best experts on this subject based on the ideXlab platform.
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Sequential erythema nodosum leprosum and reversal reaction with similar lesional cytokine mRNA patterns in a Borderline Leprosy patient.
The British journal of dermatology, 2001Co-Authors: Milton Ozório Moraes, Elizabeth P. Sampaio, Jose Augusto Da Costa Nery, B.c.c. Saraiva, Fátima De Barros Fonseca Alvarenga, Euzenir Nunes SarnoAbstract:We compare the clinical and histological data with the immunological status of a Borderline Leprosy patient who experienced an erythema nodosum leprosum (ENL) reaction followed by a reversal reaction (RR) after 12 weeks of anti-inflammatory treatment (pentoxifylline, PTX, 1200 mg daily). Skin biopsies, serum and blood samples were collected sequentially during the reactional episodes. At the outset of RR, the patient's lymphocytes secreted interferon (IFN) -gamma and there was a positive lymphoproliferative test in response to Mycobacterium leprae, which had been absent during ENL. The lepromin reaction reversed from negative (0 mm) at diagnosis, to positive (3 mm) 3 months after the development of RR. Tumour necrosis factor (TNF) -alpha levels in the serum decreased after 1 week of treatment and increased slightly thereafter. The immunohistochemical data for ENL showed a diffuse dermal and hypodermal infiltrate composed of mononuclear cells and neutrophils, while RR was characterized by an epithelioid granulomatous infiltrate with a marked presence of gammadelta T cells. Reverse transcription-polymerase chain reaction showed a mixed cytokine profile characterized by the expression of TNF-alpha, IFN-gamma, interleukin (IL) -6, IL-10 and IL-12 mRNA in the skin, which persisted throughout the development of ENL and RR lesions. IL-4 mRNA, first detected after 7 days of PTX treatment, was still present during RR. The results suggest the emergence of an initial Th0-like cytokine profile in ENL, typical of a state of immunoactivation, before conditions optimal for the appearance of an antigen-specific cell-mediated immune response and gammadelta T-cell migration are created.
H K Kar - One of the best experts on this subject based on the ideXlab platform.
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addition of mycobacterium indicus pranii vaccine as an immunotherapeutic to standard chemotherapy in Borderline Leprosy a double blind study to assess clinical improvement preliminary report
British Journal of Dermatology, 2017Co-Authors: Raj Kamal, M Natrajan, K Katoch, Vinay Kumar Pathak, Alpana Kumari, H K KarAbstract:The response of Leprosy patients to chemotherapy (WHO-Multi Drug Therapy) though generally good and predictable, exhibits variations in a section of cases. Some cases show a dramatic response while others show a slower response such variations are a reflection of the immune status of the host. This article is protected by copyright. All rights reserved.