Borderline Leprosy Patients Research Articles

Strongyloidiasis infection in a borderline lepromatous leprosy patient with adrenocorticoid insufficiency undergoing corticosteroid treatment: a case report

Strongyloidiasis is a soil-transmitted helminthiasis mainly caused by Strongyloides stercoralis. It is endemic to the tropics and subtropics. Sri Lanka has a 0-1.6% prevalence rate. S. stercoralis infection was identified in a 33-year-old Sri Lankan male patient treated with corticosteroids for borderline lepromatous leprosy with adrenocortical dysfunction. In March 2020, a 33-year-old Sri Lankan (Sinhalese) male patient presented with watery diarrhea, lower abdominal pain, and post-prandial abdominal fullness. Previously, he was diagnosed with borderline lepromatous leprosy and was treated with rifampicin, clofazimine, and prednisolone 60mg daily since July 2019. After developing gastrointestinal symptoms, he had defaulted leprosy treatment including the prednisolone for 3months. Duodenal biopsy revealed numerous intraepithelial nematodes within the lumina of glands in the duodenum whose appearance favored Strongyloides. Fecal wet smear revealed numerous Strongyloidisstercoralis L1 rhabditiform larvae. Larval tracks were seen in the agar plate culture. L3 filariform larvae of Strongyloidis stercoralis were seen in the Harada-Mori culture. In addition, the short synacthen test revealed adrenocortical insufficiency, and oral hydrocortisone and fludrocortisone were started with albendazole treatment against strongyloidiasis. Fecal wet smear and culture repeated after treatment with albendazole were negative for Strongyloidisstercoralis. The patient was discharged in July 2020 on oral hydrocortisone. Onemonth later his condition was reviewed and the repeated fecal wet smear and agar plate culture was normal. He is being followed up every 3months. This is the first case of strongyloidiasis diagnosed in a patient with borderline lepromatous leprosy from Sri Lanka. The patient manifested symptoms of strongyloidiasis while on high-dose steroid therapy for his lepromatous reaction. Subsequently, the patient not only discontinued his steroid therapy, but also developed adrenocortical insufficiency as a complication of leprosy. Therefore, although diagnosis of strongyloidiasis was delayed, his subsequent low steroid levels probably protected him from disseminated disease. This is an interesting case where symptomatic strongyloidiasis was diagnosed in a patient who was initially treated with high-dose steroids but subsequently developed adrenocortical insufficiency. We emphasize the need to screen all patients prior to the commencement of immunosuppressive therapy.

Association of Testosterone Level among Lepromatous and Borderline Leprosy Male Patients: Experience of 30 Cases in Bangladesh

Background: Hormonal dysfunction is reported among the leprosy patients.
 Objective: The purpose of the present study was to see the association of testosterone level among male patients presented with lepromatous and borderline leprosy.
 Methodology: This cross-sectional study was conducted in the Leprosy Hospital, Dhaka, Bangladesh from January to December 2016 for a period of one year. All patients with a known diagnosis of leprosy under follow up at the hospital were included in the study. The serum concentration of testosterone was measured using an enzyme immunoassay technique (ELISA) (DiaMetra, Spello, Italy).
 Result: A total number of 30 cases of leprosy were recruited for this study. The mean with SD of the study population was 39.20±9.065 years. Among 30 cases of study population 26 cases were lepromatous leprosy patents and the rest 4 cases were Borderline Leprosy patients. The mean with the standard deviation of testosterone level in serum was 6.41±4.756 mg/dL and 4.71±2.396 mg/L in lepromatous leprosy and borderline leprosy respectively (p=0.497).
 Conclusion: In conclusion there is no statistically significant relationship between leprosy and testosterone; however, lower level of testosterone is found among the study population
 Bangladesh Journal of Infectious Diseases 2020;7(2):36-39

Interleukin-17 and Interferon Gamma Serum Level Differences in Borderline Leprosy Patients

Type-1 lepra reaction commonly occurs in borderline leprosy as a result of cellular immune response toMycobacterium lepraeantigen, and it’s characterized as acute inflammation. Clinical manifestations of type-1 lepra reaction are leprosy lesions with or without ulceration, edema, neuritis, permanent nerve damage and disability. Interleukin-17 (IL-17) and interferon gamma (IFN-γ) tests in leprosy patients can help in anticipating type-1 lepra reaction that commonly causes disability. This case control study was carried out from March to July 2015 in 60 borderline leprosy patients with and without type-1 reaction at Skin and Venereal Unit of Dr. Soetomo Teaching Hospital, Surabaya, Indonesia. We used ELISAto measure IL-17 and IFN-γ levels. We found a significant IL-17 level difference between borderline leprosy patients with and without type-1 reaction (3.7 pg/mL vs. 3 pg/mL;p= 0.005). On the other hand, there was no significant IFN-γ difference between borderline leprosy patients with and without type-1 reaction (53.15 pg/mL vs. 44.15 pg/mL;p= 0.680). IL-17 had a more dominant role in type-1 lepra reaction. There was a significant IL-17 level difference between borderline leprosy patients with and without type-1 reaction.

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.

A vasculonecrotic Type 2 Lepra Reaction Mimicking Lucio Phenomenon

Multibacillary, lepromatous or borderline leprosy patients may present two types Vasculonecrotic reactions: Erythema Nodosum Leprosum (ENL) with vasculitis and Lucio Phenomenon. ENL is Type 2 Lepra Reaction while Lucio Phenomenon commonly seen in nonnodular diffuse leprosy patients, mainly reported from Mexico. Here we reported a case of 20 year old male, RFT (Relief From Treatment) leprosy patient presented with fever, malaise, joint pain, edema over hands and feet and red tender elevated nodules. Interestingly, within 3 days of admission he developed multiple vesicular erythema multiforme like eruption on chest, back and upper extremity, which broken down to form necrotic ulcer in following 4 days. Biopsy showed leucocytoclastic vasculitis and fibrin deposition in vessel walls. Furthermore, USG of both ulnar nerves showed thickening. These clinical and histopathological features helped us to arrive at the diagnosis of the ENL with vasculonecrotic phenomenon. J Microbiol Infect Dis 2019; 9(3):133-136.

A rare case of type 1 leprosy reactions following tetanus infection in a borderline tuberculoid leprosy patient and a literature review

BackgroundType 1 leprosy reaction, also known as “reversal reaction”, is related to cellular immune responses to Mycobacterium leprae antigens. The risk factors that trigger type 1 leprosy reactions are poorly understood. Leprosy with concurrent tetanus is rare, and there are no publicly available reports of a leprosy patient infected with tetanus that induced type 1 leprosy reactions.Case presentationA 56-year-old Chinese Han female presented to our hospital with symptoms of erythematous plaques and pain over her left upper limb for 2 days and foreign object sensation in her throat for 3 days. The patient had a 6-year history of leprosy. Type 1 leprosy reactions were initially considered, followed by treatment with methylprednisolone. Two days later, the patient’s symptoms were aggravated, with neck muscle tension and difficulty in opening her mouth, and the erythematous plaques had spread over most of her left upper limb. After further careful examinations, we confirmed the diagnosis of tetanus with concurrent type 1 leprosy reactions. The patient was given anti-tetanus treatment for 12 days and anti-leprosy reaction treatment for 4 months; the diseases were eventually controlled.ConclusionsThis report suggests that tetanus infection may be a trigger for type 1 leprosy reactions.

Profile of Serum Interferon Gamma Induced Protein 10 in Borderline Leprosy Patients with and without Type 1 Leprosy Reaction

Background: Leprosy reaction is an acute episode in leprosy characterized by acute inflammation sometimes accompanied with systemic symptoms. Leprosy type 1 reaction often occurs in borderline leprosy patients. Leprosy type 1 reaction can cause peripheral nerve damage through neuritis that can lead to disability. Interferon-γ induced protein 10 (IP10) is a chemokine with chemotaxis function to various immune cells such as macrophage, dendritic cells, Natural Killer cells, and activated T lymphocites. Several studies have found an increase of IP10 serum level when type 1 reaction occurred. Purpose: To evaluate the profile of IP10 serum levels in borderline patients with and without type 1 leprosy reaction. Methods: This is a descriptive cross-sectional study, with 34 borderline leprosy patients of which 17 had leprosy type 1 reaction and 17 without reaction that qualify inclusion and exclusion criteria. Results: Mean serum IP10 levels in leprosy type 1 reaction groups are 594,123 ± 327,628 pg/mL and 331,648 ± 101,819 pg/mL in groups without reaction. Conclusions: Serum IP10 levels in borderline leprosy patient with type 1 reaction is higher than patients without reaction, although confounding factors in borderline leprosy patients with type 1 reaction that can influence serum IP10 levels cannot be eliminated. Further studies are needed to reveal the role of IP`10 in type 1 leprosy reaction.

LYMPHOCYTE RESPONSE TO Mycobacterium leprae ANTIGENS IN REVERSAL REACTION STATE OF LEPROSY

Reversal Reaction (RR) in Leprosy is a sudden inflammatory episode in the chronic course of the disease due to rapid change of cellular immunological status. The aim of the study is to measure the in vitro results of Lymphocyte Stimulation Index (LSI) RR leprosy derived lymphocytes after challenged with M.leprae antigens. Twenty three Borderline Leprosy with RR and 11 Borderline Leprosy patients without RR were included in the study. Peripheral Blood Mononuclear Cells (PBMC) were separated from peripheral blood of these patients using Ficol-Hypaque column and cultured in laboratory. Using the colorimetric tetrazole (MTT) method these lymphocytes were challenged with PHA, Dharmendra antigen (1/100 and 1/10 dilutions), LAM (50 and 100 nanograms). Stimulation Index were calculated and superanatans were collected for measuring the IFN-γ and IL-10 production (ELISA). All of lymphocytes from RR patients showed higher Stimulation Index after challenged with the five M.leprae antigens compared to lymphocytes from non RR patients (p 0.05). It is concluded that lymphocytes of leprosy patients during RR state are more sensitive to antigenic stimuli compared to non-RR leprosy patients. Further extended studies are needed to determine the “cut off” value of lymphocyte Stimulation Index that is useful for clinicians in the field in the prediction of RR before starting anti leprotic treatment.

Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil.

BackgroundEvidence 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).MethodsDNA 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.ResultsThe 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0751-0) contains supplementary material, which is available to authorized users.

Diabetic status of patients with leprosy in Kuwait

The aim of this study was to screen for diabetes mellitus in leprosy patients to elucidate whether leprosy infection may play a role in the pathogenesis of diabetes mellitus in this population. Thirty patients of different ages and of both sexes with various types of leprosy were included in this study. In addition, 15 healthy individuals of comparable age and sex who had no family history of diabetes mellitus were identified as controls. In both groups, determinations of fasting and postprandial blood sugar, an oral glucose tolerance test (OGTT), measures of fasting serum insulin and pro-inflammatory cytokine tumor necrosis factor alpha (TNFα), as well as calculations using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), were carried out. Approximately 13.3% of the leprosy patients were diabetic, and 37.7% were in pre-diabetic. The highest incidences of diabetes and pre-diabetes were in lepromatous leprosy (10% and 20%, respectively); a lower incidence of pre-diabetes (6.6%) was observed in tuberculoid leprosy; and the lowest incidence of diabetes (0.0%) was noted in borderline leprosy patients. Although normal healthy persons were not diabetic (0%), 20% were pre-diabetic. This study revealed that the incidence of diabetes was higher in the leprosy patients than in the control group. As a result, we recommend that all leprosy patients should be screened for diabetes.

Oro-facial aspects of leprosy: Report of two cases with literature review

Leprosy is a chronic infectious disease affecting primarily the skin, peripheral nerves, respiratory system and the eyes. Leprosy induces various types of clinical presentation affecting the patient's immune response. Cell-mediated immunity is considered to be the crucial defence against the disease and the magnitude of this immunity defines the extent of the disease. The article presents two case reports of manifestations of leprosy in the oro-facial region, with a brief review of various other important oro-facial manifestations of leprosy. The first report deals with granulomatous nodules in the palate while the second report presents bilateral facial palsy in leprosy patients. Both the reports gain importance due to rare oral manifestation in a borderline leprosy patient in the first case, while the second case presents a rare bilateral Bell's sign. The role of the dental profession and especially the Oral Medicine specialist is of great importance in early diagnosis of oral lesions.

Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy.

A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy.

Vasculonecrotic reactions in leprosy

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.

Alteration of the cortisol–cortisone shuttle in leprosy type 1 reactions in leprosy patients in Hyderabad, India

Regulation of inflammation in leprosy may be influenced by local concentrations of active cortisol and inactive cortisone, whose concentrations are regulated by enzymes in the cortisol–cortisone shuttle. We investigated the cortisol–cortisone shuttle enzymes in the skin of leprosy patients with type 1 reactions (T1R), which are characterised by skin and nerve inflammation. Gene expression of the shuttle enzymes were quantified in skin biopsies from 15 leprosy patients with new T1R before and during prednisolone treatment and compared with levels in skin biopsies from 10 borderline leprosy patients without reactions. Gene expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2, which converts cortisol to cortisone, is down-regulated in skin from T1R lesions. However expression levels of 11β-HSD type 1, which converts cortisone to cortisol, were similar in skin with and without reactions and did not change during anti-leprosy drug treatment. Prednisolone treatment of patients with reactions is associated with an upregulation of 11β-HSD2 expression in skin. The down regulation of 11β-HSD2 at the beginning of a reaction may be caused by pro-inflammatory cytokines in the leprosy reactional lesion and may be a local attempt to down-regulate inflammation. However in leprosy reactions this local response is insufficient and exogenous steroids are required to control inflammation.

Immune reconstitution inflammatory syndrome in an HIV seropositive leprosy patient

Recent reports have described IRIS in four patients withleprosy. We report an HIV positive borderline lepromatous leprosy patient developing IRISfollowing institution of HAART.Case reportA 32-year-old male reported with numbness over upper and lower limbs in a glove andstocking pattern for the last 2 years. Over the last 6 months, he had had intermittent feverassociated with multiple crops of red raised painful evanescent lesions on the face and thelimbs. He also developed spontaneous blistering, slippage of footwear and difficulty in doingfine work with his hands. He had progressive weight loss over the past 2 years withoutpersistent diarrhoea, cough or other systemic complaints. He denied high risk behaviourtowards the acquisition of HIV infection.The patient was febrile with multiple discrete submandibular, axillary and inguinal non-tender and mobile lymph nodes. Cutaneous examination revealed marked seborrhoea overface and chest with diffuse infiltration of the forehead and ears. Multiple erythematous tender

Expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions.

In the response to T-helper cell (Th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (NO) are produced by activated macrophages expressing the inducible NO synthase (iNOS). The role and importance of reactive nitrogen intermediates (RNIs) such as NO and peroxynitrite in the host response to diseases caused by intracellular pathogens such as Mycobacterium leprae and M. tuberculosis is unclear. The aim of this study was to investigate the presence of local production of NO and peroxynitrite in borderline leprosy by using antibodies against iNOS and the product of peroxynitrite, nitrotyrosine (NT). We detected the presence of iNOS and NT in skin biopsies from borderline leprosy patients, with and without reversal reaction (RR), by immunohistochemistry (n = 26). In general, the granulomas from borderline leprosy lesions with and without RR showed high and specific expression of iNOS and NT. Moreover, strong immunoreactivity to iNOS and NT was observed in granulomas surrounding and infiltrating dermal nerves. The expression of iNOS and NT was also strong in keratinocytes, fibroblasts and endothelial cells in close relation to the granulomatous reaction. In contrast, normal human skin showed no expression of iNOS and NT in these cells. We conclude that iNOS and NT are expressed in granulomas from borderline leprosy patients with and without RR and propose that RNIs might be involved in the nerve damage following RR in leprosy.

Evaluation of three Mycobacterium leprae monoclonal antibodies in mucus and lymph samples from Ziehl-Neelsen stain negative leprosy patients and their household contacts in an Indian community.

Mucus and lymph smears collected from leprosy patients (9) and their household contacts (44) in the Caño Mochuelo Indian Reservation, Casanare, Colombia, were examined with monoclonal antibodies (MoAb) against Mycobacterium leprae. The individuals studied were: 5 borderline leprosy (BB) patients, 4 with a lepromatous leprosy (LL), all of whom were undergoing epidemiological surveillance after treatment and 44 household contacts: 21 of the LL and 23 contacts of the BB patients. The MoAb were reactive with the following M. leprae antigens: 65 kd heat shock protein, A6; soluble antigen G7 and complete antigen, E11. All the samples were tested with each of the MoAb using the avidin-biotin-peroxidase technique and 3,3 diaminobenzidine as chromogen. The patients and household contacts studied were all recorded as Ziehl-Neelsen stain negative. The MoAb which showed optimal reaction was G7, this MoAb permitted good visualization of the bacilli. Five patients with BB diagnosis and one with LL were positive for G7; of the BB patients' household contacts, 9 were positive for G7; 7 of the LL patients' household contacts were positive for the same MoAb. MoAb G7 allowed the detection of bacillar Mycobacterium spp. compatible structures in both patients and household contacts. G7 permitted the visualization of the complete bacillus and could be used for early diagnosis and follow-up of the disease in patients.

Anti-neutrophil cytoplasmic autoantibodies in leprosy.

The objective was to evaluate the frequency of cytoplasmic and peripheral antineutrophil cytoplasmic antibodies (ANCA) in patients with leprosy, and to correlate the presence of ANCA with type and disease activity. Consecutive patients with leprosy were assessed clinically, and IgG ANCA were measured by indirect immunofluorescence. The presence of three of the following was used to assess disease activity: reactional state, fever, new cutaneous lesions, erythrocyte sedimentation rate and C-reactive protein. Sixty-four patients were studied and divided according to the Ridley-Jopling classification: of 38 patients with lepromatous leprosy, eight (21%) had perinuclear (p) ANCA and two (6%) had cytoplasmic ANCA. ANCA titres ranged from 1:20 to 1:320. Of six borderline leprosy patients, one (16%) had p-ANCA. All 20 tuberculoid leprosy patients and 65 healthy control subjects had negative ANCA. There was no correlation between ANCA titres and disease activity in positive patients. ANCA, mainly those with a perinuclear pattern, may be present in leprosy, especially in the lepromatous pole. This disease should be added to the spectrum of diseases with ANCA positivity.

Type 1- and Type 2-Like Lesional Skin-DerivedMycobacterium leprae-Responsive T Cell Clones Are Characterized by Coexpression of IFN-γ/TNF-α and IL-4/IL-5/IL-13, Respectively

AbstractIn an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN-γ and IL-4 expression. To explore whether other cytokines are coproduced along with IFN-γ and IL-4, we investigated the secretion of a panel of other cytokines (TNF-α, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-γ/TNF-α (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-γ/TNF-α, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.

Reversal reaction in borderline leprosy is associated with a polarized shift to type 1-like Mycobacterium leprae T cell reactivity in lesional skin: a follow-up study.

Borderline leprosy patients often undergo acute changes in immune reactivity that manifest as reversal reaction (RR) in the course of the disease. RR is associated with an exacerbated local delayed-type cellular immune response to Mycobacterium leprae and is responsible for severe tissue damage. We investigated whether RR episodes are associated with a change in T cell subsets in the lesional skin with regard to their cytokine secretion profiles. M. leprae-responsive T cell lines and thereafter T cell clones (TCC) were generated from the lesional skin of seven untreated borderline leprosy patients (with or without RR) and again from three of these patients experiencing RR during treatment. The phenotypes of the M. leprae-responsive TCC were either CD4+, CD8+, CD4-/CD8+/TCR gammadelta+, or CD4-/CD8-/TCR gammadelta+, although most of them were CD4+. Regardless of the clinical status of the untreated patients, a major subset of the M. leprae-responsive TCC was type 0-like and produced both IFN-gamma and IL-4. Interestingly, in all three patients who experienced a (re)occurrence of RR during treatment after the first analysis, a clear shift to polarized IFN-gamma production by the M. leprae-responsive TCC (type 1-like) was observed. This shift in T cell subsets was also reflected in the observed decrease in serum IgG and IgM levels of the same patients during RR. These finding indicate that CD4+ M. leprae-responsive T cells with a polarized type 1-like phenotype might be responsible for the immune-mediated tissue damage occurring during RR.