Lepromatous Leprosy Research Articles

Analysis of histomorphological study in Hansen’s disease: A hospital based study done in rural population

Leprosy, also known as Hansen’s disease is a chronic infectious disease caused by Mycobacterium Leprae. It still continues to be a major public health problem in India. AIM: The study was aimed at analysing the histomorphological features of leprosy in skin biopsies and based on histological findings they were categorised according to Ridley-Joplings classification. Clinical correlation was also done wherever possible. Materials and methods: After adequate fixation of skin biopsies with 10% formalin, routine processing was done and tissue embedded in paraffin section of 5µ thickness and then stained with Hematoxylin and Eosin (H&E) and Fite-Faraco stain, subsequently studied under microscope. Results: Total of 35 skin biopsies were studied, with the mean age of presentation ranging from 14-72 years, showing male predominance. Boderline tuberculoid (37.14%) was the most common type. Atrophic epidermis was seen only in 9 cases but Grenz zone was present in all 12 cases of Lepromatous leprosy. Epithelioid granuloma is the commonest finding in Boderline Tuberculoid type. Clinico histomorphological correlation was made in 23 cases and discoherence was found in remaining 12cases. Conclusion: Correlation of clinical and histopathological features along with bacteriological index plays a pivotal role for accurate typing and for prognostication. Clinicopathological concordance is highest in polar forms, and being least in Indeterminate Leprosy (IL).

Erythema nodosum as Leprosy reaction

Purpose.To present a clinical case of leprosy exacerbation on the background of ongoing therapy.
 Materials and methods.A 52-year-old patient with a diagnosis of "lepromatous (cutaneous) leprosy, leprosy LL" (multi-bacterial leprosy, lepromatous form, active stage), has an exacerbation in the form of nodular erythema at 3.5 years after the start of treatment. Due to the exacerbation of the leprosy process, dexamethasone therapy was performed intravenously in a dose of 4 mg/ml 3.0 ml + 0.9% NaCl 200.0 ml daily No. 10.
 Results. An exacerbation was diagnosed leprosy nodular erythema. The prescription of adequate therapy led to a complete regression of clinical manifestations.
 Conclusion.The described case is presented in connection with the rarity of this dermatosis.

Report of two cases of lepromatous leprosy at an early age

Leprosy is an infectious disease that has a broad spectrum of clinical manifestations. Lepromatous leprosy has a deficient cellular immune response and high bacillary multiplication. It has epidemiological importance, as it is the most contagious clinical form of the disease. Its manifestation in children and adolescents is unusual. In the present study, we report two cases of leprosy at an early age, manifesting the lepromatous clinical form, highlighting the auricular involvement in one case. Early diagnosis is an essential tool to avoid deformities and deficiencies.

Characteristics of Oral Lesions in Patients With Hansen Disease

Background and objectiveHansen disease, or leprosy, is caused by Mycobacterium leprae or Mycobacterium lepromatosis. Because these bacteria enter the body via the upper airways, they generate clinical manifestations in the nasal mucous membranes and the mouth. We aimed to describe the characteristics of oral lesions in patients with Hansen disease. Material and methodsCross-sectional observational study of 100 patients diagnosed with Hansen disease. We examined the oral cavity and recorded clinical findings on a disease reporting form for each patient. We also included the histopathologic findings for lesions that required a biopsy. Samples suggestive of Hansen disease were processed with hematoxylin-eosin, Ziehl–Neelsen, and Fite–Faraco staining. Variables were analyzed, as appropriate, with the χ2 test, the Mann-Whitney U test, or the Spearman correlation coefficient. ResultsSixty-seven men and 33 women were included. The mean (SD) age was 48.1 (16.4) years. Thirty-four patients had oral lesions. Lesions related to Hansen disease were found in 9 patients. The locations were the hard palate and upper lip. Oral lesions were significantly more frequent in patients with lepromatous leprosy, borderline lepromatous leprosy (P = .029), and erythema nodosum leprosum (P = .031). ConclusionsThe frequency of oral lesions is low in Hansen disease. Such lesions present as lepromas and leprous plaques on the hard palate and upper lip.

Lucio’s phenomenon in untreated advanced leprosy

A 77-year-old woman with underlying diabetes mellitus, hypertension and Parkinson disease presented to the emergency department with burn injury after dipping her foot into hot water. She was admitted with 75% dermal thickness burn of bilateral foot. On examination, she was noted to have extensive purpuric patches with livedo reticularis. Further examination revealed leonine facies, madarosis and hypoaesthesia of the lower limbs. Slit skin smear exhibit bacillary index of 3.5 (moderate acid-fast bacteria present). Skin biopsy showed perivascular lymphocytic and foamy histiocytic inflammation with vascular thrombosis (Fig. 1; H&E, 100×) and presence of acid-fast bacilli (Fig. 2; Ziehl-Neelsen stain, 400×), features that are consistent with lepromatous leprosy with Lucio’s phenomenon. This patient was started on antileprosy multidrug therapy (clofazimine, rifampicin and dapsone). However, she developed multiple ulcers, pressure sores and had recurrent infections while in ward stay that required multiple antibiotics regime and daily dressing. She succumbed 3 months following admission due to septic shock secondary to infected ulcers.

A HISTOPATHOLOGICAL STUDY OF LEPROSY ALONG WITH CLINICAL CORRELATION.

Background: Leprosy or Hansen’s disease is a chronic infectious disease that mainly affects skin and peripheral nerves. Histopathology and demonstration of lepra bacilli is an essential tool to supplement clinical examination and diagnosis for correct classification and therefore treatment of patients. Aim: To study histopathology of leprosy cases and identify histological types in patients in a tertiary care centre, Asram hospital in Eluru. Materials and Methods: 18 skin biopsies diagnosed as leprosy over a period of two years from January 2018 to December 2019 were studied. Haematoxylin-eosin and Fite-Faraco staining for demonstrating lepra bacilli were done. Results: Male to female ratio of patients was 4.5:1. Maximum number of cases was seen in the 3rd and fourth decades of life. The commonest histological type was borderline tuberculoid (5 cases, 28%) and indeterminate type, lepromatous type (3 cases, 16%); followed by tuberculoid leprosy and erythema nodosum leprosum (2 cases, 11%), the least common cases were of lepromatous leprosy to borderline tuberculoid leprosy (1cases, 6%). The most common site was upper limb (26%). All 3/18(24%) patients with affected nerves showed ulnar and auricular nerve involvement. Hypopigmented, anaesthetic plaque was the commonest clinical feature followed by erythematous lesions. All cases of borderline tuberculoid, borderline lepromatous, lepromatous, midboderline and indeterminate showed acid-fast bacilli on Fite stain. Tuberculoid cases showed well-formed granulomas, borderline tuberculoid type showed additional feature of giant cells and lepromatous types showed grenz zone and no granulomas. Conclusion: Histopathological examination is the gold standard for accurate diagnosis and typing of leprosy. It should be done in all leprosy cases presenting to the clinician.

The Clinical Trend of Leprosy from 2000 to 2016 in Kaohsiung, a Major International Harbor City in Taiwan, Where Leprosy is Almost Eradicated.

Leprosy is a socially stigmatized granulomatous skin disease caused by Mycobacterium leprae. Due to improvements in medicine and hygiene in Taiwan, the incidence is very low, up to one dozen per year; however, leprosy has never been eradicated due to the increased numbers of immigrants from Southeast Asia. This study aimed to characterize the clinical and histopathological features of patients with leprosy in the context of near elimination. Fifteen cases of pathologically proven leprosy were identified from 2000 to 2016 in Kaohsiung Chang Gung Memorial Hospital. The clinical presentations, demographic details, treatment responses, and disease outcomes were reviewed. The mean age was 46 years (range: 26-73 years). Eight cases were native Taiwanese, while 6 cases and 1 case involved foreign workers from Indonesia and Thailand, respectively. The diagnosis was made 3-6 months on average after skin lesions appeared. The most common clinical subtype was lepromatous leprosy (n = 7). Ten patients were multibacillus microscopically. Three cases were deported. The remaining 12 patients received dapsone and rifampicin for 12 months without recurrence to date. In the near leprosy-eradicated country, early diagnosis and physician vigilance are critical in disease control. Immigrants from endemic countries require strict and professional dermatological examinations and regular follow-up.

4,4'-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor.

The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.

Association of IL-10 Gene Polymorphism With IL-10 Secretion by CD4 and T Regulatory Cells in Human Leprosy.

Leprosy is a chronic bacterial disease caused by Mycobacterium leprae. Cytokines are known to play vital role as a peacekeeper during inflammatory and other immunocompromised conditions such as leprosy. This study has tried to bridge the gap of information on cytokine gene polymorphisms and its potential role in the pathogenesis of leprosy. Interleukin-10 (IL-10) is an immunosuppressive cytokine, found to be elevated in leprosy that accounted for the suppression of host’s immune system by regulating the functions of other immune cells. T helper cells and T regulatory (Tregs) cells are the major source of IL-10 in lepromatous leprosy patients. In this study, we have documented the association of IL-10 cytokine gene polymorphism with the disease progression. A total of 132 lepromatous leprosy patients and 120 healthy controls were analyzed for IL-10 cytokine gene polymorphisms using PCR-SSP assay and flow cytometry was used to analyze IL-10 secretion by CD4 and Tregs in various genotype of leprosy patients. The frequencies of IL-10 (-819) TT and IL-10 (-1082) GG genotypes were significantly higher in leprosy patients as compared to healthy controls. This observation advocates that these genotypes were associated with the susceptibility and development of the disease. In addition, flow cytometry analysis demonstrated an increased number of IL-10 producing CD4 and Treg cells in IL-10 (819) TT genotype compared to CT and CC genotypes. These observations were further supported by immunohistochemical studies. Therefore, we can conclude that IL-10 cytokine gene polymorphisms by affecting its production can determine the predilection and progression of leprosy in the study population.

Coexistence of mycobacterial infections \u2013 Mycobacterium tuberculosis and Mycobacterium leprae \u2013 in Sri Lanka: a case series

BackgroundLeprosy is one of the oldest mycobacterial infections and tuberculosis is the most common mycobacterial infection with a higher degree of infectivity than leprosy. Although both diseases are prevalent in clusters in developing countries, simultaneous occurrence of them in an individual is a rare entity, even in an endemic setting.Case presentationWe describe six cases of tuberculosis and leprosy coinfection: a 57-year-old Sinhalese woman, a 47-year-old Tamil woman, a 72-year-old Tamil man, a 59-year-old Sinhalese man, a 54-year-old Sinhalese man, and a 50-year-old Sinhalese man. In this case series, five patients had lepromatous leprosy and the majority of patients were men. Three patients were detected to have tuberculosis at the outset of treatment of leprosy, while two developed tuberculosis later and one had extrapulmonary tuberculosis 5 years before the diagnosis of leprosy. The latter developed pulmonary tuberculosis as a reactivation while on treatment for leprosy. A majority of our patients with pulmonary tuberculosis had positive Mantoux test, high erythrocyte sedimentation rate, radiological evidence, and acid-fast bacilli in sputum. Human immunodeficiency virus and diabetes were detected in one patient. One patient had rifampicin-resistant tuberculosis, while she was on monthly rifampicin therapy for leprosy.ConclusionAn immunocompromised status, such as human immunodeficiency virus infection, diabetes, and immunosuppressive drugs, are risk factors for tuberculosis infection. The use of steroids in the treatment of leprosy may increase the susceptibility to develop tuberculosis. Development of rifampicin resistance secondary to monthly rifampicin in leprosy is a major concern in treating patients coinfected with tuberculosis. Despite the paucity of reports of coinfection, it is advisable to screen for tuberculosis in patients with leprosy, especially if there are respiratory or constitutional symptoms, high erythrocyte sedimentation rate, and abnormal chest X-ray. The fact is that positive Mantoux and QuantiFERON Gold tests and presence of acid-fast bacilli in sputum are misleading, chest X-ray evidence of active tuberculosis and positive tuberculosis cultures are important diagnostic clues for active tuberculosis infection in a patient with leprosy. This is important to avoid monthly rifampicin in patients with suspected coinfections, which may lead to development of drug resistance to tuberculosis treatment. Whether prolonged steroid therapy in leprosy is a risk factor for development of tuberculosis is still controversial.

Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.

To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by FcγR cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression.

Lesional fine needle aspiration (FNA) cytology in reactional and non-reactional leprosy patients

Fine needle aspiration cytology (FNAC) is a relatively simpler tool as compared to histopathology for the evaluation of the cytomorphology of skin lesions. Fifty consecutive leprosy patients diagnosed and classified according to Ridley Jopling scale1 were taken to study the cytomorphology of leprosy lesions in fine needle aspirates and correlate it with their histopathology by a skin biopsy from the same site for histopathological examination after H/E staining. Borderline leprosy patients with Type I reaction showed significantly more numbers of giant cells, collagen and elastin in their smears as compared to those without reaction. The smears were more heavily cellular with fragmented collagen and elastin along with significant increase in neutrophils in patients with Type II reaction while foamy macrophages with fatty background were common in non-reactional lepromatous leprosy patients. A complete correlation between histopathological and cytomorphological findings was observed in 79.4% of cases.

Caracterización de lesiones bucales de pacientes con enfermedad de Hansen

Background and objectiveHansen disease, or leprosy, is caused by Mycobacterium leprae or Mycobacterium lepromatosis. Because these bacteria enter the body via the upper airways, they generate clinical manifestations in the nasal mucous membranes and the mouth. We aimed to describe the characteristics of oral lesions in patients with Hansen disease. Material and methodsCross-sectional observational study of 100 patients diagnosed with Hansen disease. We examined the oral cavity and recorded clinical findings on a disease reporting form for each patient. We also included the histopathologic findings for lesions that required a biopsy. Samples suggestive of Hansen disease were processed with hematoxylin-eosin, Ziehl–Neelsen, and Fite–Faraco staining. Variables were analyzed, as appropriate, with the χ2 test, the Mann-Whitney U test, or the Spearman correlation coefficient. ResultsSixty-seven men and 33 women were included. The mean (SD) age was 48.1±16.4 years. Thirty-four patients had oral lesions. Lesions related to Hansen disease were found in 9 patients. The locations were the hard palate and upper lip. Oral lesions were significantly more frequent in patients with lepromatous leprosy, borderline lepromatous leprosy (P = .029), and erythema nodosum leprosum (P = .031). ConclusionsThe frequency of oral lesions is low in Hansen disease. Such lesions present as lepromas and leprous plaques on the hard palate and upper lip.

Evaluation of agreement between clinical and histopathological diagnosis of subtype of leprosy by skin punch biopsy

Introduction: Leprosy is chronic granulomatous disease caused by Mycobacterium leprae. Clinically diagnosed cases of leprosy can be evaluated by punch biopsy. It can be classified according to Ridley and Jopling Classification.
 Objective: To study the different spectrum of leprosy and its Bacillary Index (BI), evaluate the agreement between clinical and histopathological diagnosis.
 Materials and Methods: This is a hospital based cross sectional retrospective study done for the period of 6 months from January to June 2019. The data were subjected to kappa analysis by using SPSS version 24 to see the agreement between clinical and histopathological diagnosis.
 Results: Out of 62 cases of clinically diagnosed cases of leprosy three (4.83%) cases turned out to be other granulomatous diseases. According to Ridley and Jopling classification, clinical and histopathological agreement was seen in 38 (61.29%) cases. Agreement of 100% was seen in Indeterminate leprosy (IL) and Borderline tuberculoid leprosy (BT). The BI was more in Lepromatous leprosy (LL), Borderline lepromatous (BL) whereas IL, BT and Tuberculoid leprosy (TT) showed less BI. Overall there was moderate agreement between clinical and histopathological diagnosis (kappa- 0.505) which was statistically significant (p value <0.05).
 Conclusion: There was moderate agreement between the clinical and histopathological diagnosis of subtype of leprosy. The Bacillary load was high in LL whereas least in TT and is determined by immune system.

Relationship Between sCD163 and mCD163 and Their Implication in the Detection and Typing of Leprosy.

BackgroundLeprosy is a chronic contagious disease caused by Mycobacterium lepraea. CD163 is a monocyte trans-membrane glycoprotein receptor (mCD163) that sheds from the cell surface and circulates as a soluble (serum) form (sCD163). Changes in the mCD163 and sCD163 levels could mirror the categorization of inflammatory procedure, demonstrating a possible use of CD163 as a diagnostic indicator of inflammation.ObjectiveTo investigate the possible role of CD163 (sCD163 and mCD163) in leprosy pathogenesis and to assess whether CD163 is a helpful inflammatory marker of leprosy development and typing.Patients and MethodsThis case control study included 70 leprosy patients and 30 healthy controls. Leprosy patients were classified according to the Madrid criteria (1953) into: tuberculoid leprosy (TT), border-line leprosy (BL), and lepromatous leprosy (LL). For all participants, complete blood count (CBC), serum CD163 using ELISA and monocytes positive for CD163 using flow cytometry were done.ResultsLeprosy patients had significantly low WBCs and platelet counts (p<0.001) and had significantly higher sCD163 (p=0.025) and mCD163 (p=0.042) that were highest in LL followed by BL, then TT patients (p<0.001). There was a significant positive correlation between mCD163 and sCD163 levels in leprosy patients (r=0.896, p<0.001). ROC analysis revealed a significant role of serum sCD163 and of mCD163 positive monocytes in the detection (p<0.001) and typing of leprosy (p=0.002 and p<0.001, respectively).ConclusionBoth sCD163 and mCD163 positive monocytes may have an active role in leprosy pathogenesis. They could be potential biomarkers for leprosy detection and typing.

Elephantiasis nostras verrucosa secondary to leprous lymphadenopathy; a case report

Leprosy has earned the status of ‘great imitator’ considering its ability to present in wide array of manifestations. Typical neuro-dermatological features are easy to recognize but uncommon presentations frequently delay the diagnosis. Here we report a 60-years-old lady presenting with elephantiasis nostras verrucosa secondary to lepromatous leprosy. In the post elimination era, it is important to have a high index of suspicion to prevent delay in diagnosis.

Single-cell RNA-sequencing of leprosy skin lesions reveals a titin (TTN) expressing T cell subset associated with the progressive disease

Abstract The immune response to intracellular bacteria is critical for host defense against the invading pathogen. This interaction can be studied in the human disease leprosy caused by the intracellular bacterium Mycobacterium leprae affecting primarily the skin compartments. Patients with tuberculoid leprosy (T-lep) express a Th1 cytokine pattern in skin lesions and develop a protective immunity that eliminates the infection, whereas those with lepromatous leprosy (L-lep) express Th2 cytokines in lesions and sustain a progressive infection. In the reversal reaction (RR) state, patients upgrade, either spontaneously or during chemotherapy, from the L-lep to the T-lep pole. Herein, we used unbiased single-cell RNA-sequencing to explore the breadth of potential immune cell states in leprosy. Unexpectedly, we identified a lymphocyte cluster marked by expression of titin (TTN), which is commonly found in the sarcomere of muscle cells. TTN+ T cells were predominantly enriched in L-lep lesions and RNA-FISH showed a higher number of TTN mRNA dots on CD3+ T cells from L-lep in comparison with RR patients. TTN gene expression decreased in the skin lesion cells of L-lep patients undergoing RR episodes associated with the onset of therapy. Protein expression was confirmed by analysis of T cell clones isolated from leprosy lesions and blood-derived CD3+ T cells from healthy donors. Indeed, immunohistochemical staining of lesions and healthy tonsil showed that TTN was present in the CD3+ T cell zones. Canonical pathways analysis revealed that TTN might be involved with T cell inhibitory RhoA signaling pathway. The role of TTN on T cells remains unknown, however, it could represent a novel mechanism in the skin immune response against cutaneous pathogens.

Molecular epidemiology and transmission dynamics of leprosy among multicase families and case-contact pairs

BackgroundHuman-to-human transmission of Mycobacterium leprae among household contacts of active leprosy cases is significant, and surveillance of household contacts is vital to interrupting the transmission chain for this disease. This study was conducted to identify similarities in M. leprae strains, based on genomic single nucleotide polymorphisms (SNPs), among cases and their household contacts and in multicase families in order to decipher possible associations, transmission links, various clinical conditions of index cases that enhance person-to-person transmission, and timelines for transmission patterns. MethodsPCR for M. leprae DNA detection (amplification of the Rlep gene) and SNP subtyping of M. leprae strains was performed for 61 index cases and one of their household contacts. Additionally, we studied six families with multiple cases of leprosy, to understand timelines of infectivity and its relation to severity of the disease in the index cases. ResultsIndex cases with lepromatous (LL) and borderline lepromatous (BL) leprosy, together with a positive bacteriological index (BI) for M. leprae, result in a higher percentage of their contacts subclinically infected with M. leprae, with odds ratios (OR) of 6.6 (95% confidence interval (CI) 1.6–27.6) for BL and LL, and 7.07 (CI 1.41–35.41) for BI-positive index cases. 75% of the case–contact pairs had a similar SNP subtype of M. leprae. The timeline of infection in multicase families revealed that contacts were infected during the BI-positive period of the index case. ConclusionUsing molecular methods, we determined that positivity for M. leprae DNA in contacts of index leprosy cases was attributed to clinical characteristics of leprosy in the index cases. LL and BL forms of leprosy, together with positive BI, contributed to dissemination of infection to household contacts. In conclusion, we found a relationship between SNP subtypes within index case–contact pairs. This method can help decipher the transmission patterns and identify individuals at risk of contracting leprosy.

ER Stress Regulates Immunosuppressive Function of Myeloid Derived Suppressor Cells in Leprosy that Can Be Overcome in the Presence of IFN-γ.

SummaryMyeloid derived suppressor cells (MDSCs) are a population of immature myeloid cells that suppress adaptive immune function, yet the factors that regulate their suppressive function in patients with infection remain unclear. We studied MDSCs in patients with leprosy, a disease caused by Mycobacterium leprae, where clinical manifestations present on a spectrum that correlate with immunity to the pathogen. We found that HLA-DR-CD33+CD15+ MDSCs were increased in blood from patients with disseminated/progressive lepromatous leprosy and possessed T cell-suppressive activity as compared with self-limiting tuberculoid leprosy. Mechanistically, we found ER stress played a critical role in regulating the T cell suppressive activity in these MDSCs. Furthermore, ER stress augmented IL-10 production, contributing to MDSC activity, whereas IFN-γ allowed T cells to overcome MDSC suppressive activity. These studies highlight a regulatory mechanism that links ER stress to IL-10 in mediating MDSC suppressive function in human infectious disease.

A case of lepromatous leprosy

This article describes a clinical case of lepromatous leprosy. Despite the sporadic incidence of leprosy in Russia, the presented clinical observation demonstrates that clinicians must maintain vigilance with regard to leprosy. Close attention and in-depth study of the history of the disease is required both in endemic and (in view of active migration and tourist flows) non-endemic regions, since timely diagnosis of this mycobacteriosis can present significant difficulties.