Analysis of Antibody and Cytokine Markers for Leprosy Nerve Damage and Reactions in the INFIR Cohort in India

Abstract

BackgroundThe 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 StudyAntibodies to mycobacteria, nerve components and serum cytokine were measured as potential markers for their possible association with reactions and NFI.Patients and Methods303 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.ResultsS-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.ConclusionThese 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.

Association of tumor necrosis factor-alpha and interferon gamma gene polymorphisms and their plasma levels in leprosy, HIV and other peripheral neuropathies

“…Elevated levels of TNF-a and IFN-c have been observed in leprosy and in lepra reactions [10,13,27]. The present study also showed elevated TNF-a and IFN-c levels in LN patients which could be due to exaggerated cell mediated immunity (CMI) that can lead to both a beneficial effect of clearing of bacilli as well as the adverse effect of producing demyelination and subsequent loss or impairment of nerve function [6]. There was no significant difference in the levels of plasma TNF-a and IFN-c between PB and MB cases suggesting that neuropathy in leprosy involves both cytokines to the same extent though they present different bacterial load and clinical classification.…”

“…Association of A/A homozygous genotype was also observed in HIV-PN as compared to HIV group (p < 0.05, OR = 6.5, CI = 2. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. When LN group was segregated we found a significant association of IFN-c +874 A/A genotype in MB leprosy group (p < 0.05, OR = 8, CI = 3.1-21) and not in PB group as compared to HS.…”

“…Globally, newly detected cases of leprosy was 215,656 in 2013 and India contributed 58% of the total load [4]. Invasion of Mycobacterium leprae and the molecular events occurring at the Schwann cell level trigger cell and antibody mediated immune responses which perpetuate the PN [5,6] together affect a wide range of 30-67% of patients with HIV [7]. The neuropathy is either mediated by the virus directly [8] or as a side effect due to the use of combination antiretrovirals [9].…”

Antibodies to Myelin P0 and Ceramide Perpetuate Neuropathy in Long Standing Treated Leprosy Patients

“…This evidence of increased auto antibodies to myelin and glycosphingolipid components of nerve in treated leprosy patients indicates that nerve damage continues as an autoimmune response to multiple nerve components even after a patient has completed leprosy treatment [25,38]. In a study of 303 multibacillary leprosy patients, ceramide antibody was elevated in patients with old sensory nerve damage [39] suggesting that autoantibodies may not be involved in the initiation of nerve damage but play an important role in the propagation of nerve damage. During the course of treatment and thereafter, various nerve antigens may be presented to the immune system which trigger autoimmune mechanisms whereby nerve damage is perpetuated.…”

Integrative literature review of the reported uses of serological tests in leprosy management

“…Corollarily, as patients with impaired nerve function typically have high levels of anti-PGL-I IgM and IgG, serological evaluation may also assist in identifying individuals with nerve damage ( Table 3). The association between high antibody titers and nerve damage highlights the need to detect and treat serologically positive individuals as soon as possible (45) . Serum antibodies can also be a useful measure of the effectiveness of treatments (4) (26) (27) ( Table 3).…”