Dataset Information

Analysis of antibody and cytokine markers for leprosy nerve damage and reactions in the INFIR cohort in India.

ABSTRACT:

Background

The ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment (NFI) in leprosy.

Aim of the study

Antibodies to mycobacteria, nerve components and serum cytokine were measured as potential markers for their possible association with reactions and NFI.

Patients and methods

303 newly diagnosed leprosy patients from two centres in North India were enrolled. Antibodies to PGL-1, LAM (IgG1 and IgG3), ceramide, S100 and TNFα levels were measured using ELISA techniques.

Results

S-100, PGL IgG and IgM antibody levels were lowest in patients with BT leprosy and highest in patients with lepromatous leprosy. LAM IgG1 and LAM IgG3 antibody levels were highest in patients with BL leprosy. Ceramide antibody levels were not correlated with type of leprosy. Levels of all the antibodies tested and TNF α were lowest in patients with only skin reaction. PGL IgM antibody levels were elevated in patients with skin reactions and NFI. Old sensory NFI is associated with significant elevation of PGL IgG, LAM IgG and S100 antibody levels.

Conclusion

These results reveal that the antibody response to mycobacterial antigens, nerve antigens and cytokines are in a dynamic flux and could collectively contribute to NFI in leprosy. The association of multiple markers with old NFI may indicate the contribution of different pathological processes.

SUBMITTER: Jadhav R

PROVIDER: S-EPMC3050910 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Analysis of antibody and cytokine markers for leprosy nerve damage and reactions in the INFIR cohort in India.

Jadhav Rupendra R Suneetha Lavanya L Kamble Ravindra R Shinde Vidyagouri V Devi Karuna K Chaduvula Meher Vani MV Raju Renuka R Suneetha Sujai S Nicholls Peter G PG van Brakel Wim H WH Lockwood Diana N J DN

PLoS neglected tropical diseases 20110308 3

<h4>Background</h4>The ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment (NFI) in leprosy.<h4>Aim of the study</h4>Antibodies to mycobacteria, nerve components and serum cytokine were measured as potential markers for their possible association with reactions and NFI.<h4>Patients and methods</h4>303 newly diagnosed leprosy patients from two centres in North India were enrolled. Antibodies to PGL-1, LAM ...[more]

PMID: 21408123

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Project description:BackgroundLeprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R.MethodologyRandomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome.Principal findings345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia.ConclusionsAzathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them.Trial registrationClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number-REFCTRI/2016/12/007558.

Project description:BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/principal findingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/significanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

Project description:BackgroundLeprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions.MethodologyIgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time.Principal findingsAmong these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0<BI<3, (36 RR, 36 reaction-free), higher antibody levels to PGL-I (p = 0.014) and to LID-1 (p = 0.035) were seen in RR while difference in anti-ND-O-LID positivity was borderline (p = 0.052). Patients with BI≥3 that developed ENL had higher levels of anti-LID-1 antibodies (p = 0.028) compared to reaction-free patients. Anti-PGL-I serology had a limited predictive value for RR according to receiver operating curve/ROC analyses (area-under-the-curve/AUC = 0.7). Anti LID-1 serology at baseline showed the best performance to predict ENL (AUC 0.85).ConclusionsOverall, detection of anti-PGL-I, anti-LID-1 and anti-ND-O-LID antibodies at diagnosis, showed low sensitivity and specificity for RR prediction, indicating low applicability of serological tests for RR prognosis. On the other hand, anti-LID-1 serology at diagnosis has shown prognostic value for ENL development in BI positive patients.Trial registrationClinicalTrials.gov NCT00669643.

Dataset Information

Analysis of antibody and cytokine markers for leprosy nerve damage and reactions in the INFIR cohort in India.

Background

Aim of the study

Patients and methods

Results

Conclusion

Publications

Analysis of antibody and cytokine markers for leprosy nerve damage and reactions in the INFIR cohort in India.

Similar Datasets

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