Evaluation of the autoimmune response in leprosy

Kroumpouzos, G; Vareltzidis, A; Konstadoulakis, Manoussos M.; Avgerinou, Georgia; Anastasiadis, Georgios; Kroubouzou, H.; Panteleos, A; Tosca, Androniki

doi:10.5935/0305-7518.19930022

Cited by 9 publications

(6 citation statements)

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“…In this study, however, they were detected also in DLE patients without systemic disturbances, although in relatively lower titers. This is in accordance with previous reports on the detection of anti-cl Abs in DLE [16,25,26], vascular diseases [27] and also in acute and chronic infectious diseases [28,29]. Il seems therefore, that anti-cl Abs are not always indicative of systemic vascular manifestations.…”

Section: Discussionsupporting

confidence: 93%

Autoantibody profile in cutaneous lupus erythematosus subsets: correlations between various autoantibodies of the same isotype

Kroumpouzos

Tosca

Konstadoulakis

et al. 1994

Acad Dermatol Venereol

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The objective of the present study was an extensive analysis of the autoantibody profile in the most eommon subsets of cutaneous lupus erythematosus (LE), acute and subacute cutaneous lupus erythematosus (ACLE, SCLE) as well as discoid lupus, localized or disseminatus (DLE loc, DLE dis). Antibodies (Abs) against glomerular extracts, actin, myosin and cardiolipin were examined in the various cutaneous lupus subgroups, in addition to ANA and Abs against DNA, ENA and IgG (rheumatoid factor). Abs against glomerular extracts were detected mainly in ACLE and SCLE, whereas Abs against actin, myosin and cardiolipin were found in all cutaneous lupus subsets. The detailed record of the autoantibody profile helped in the serological differential diagnosis of the various cutaneous lupus subsets, suggesting also that SCLE and DLE dis are distinct subsets in the spectrum of cutaneous LE. Finally, correlations between autoantibodies of the same isotype were carried out, providing implieations for regulation of autoantibody production.

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Section: Discussionsupporting

confidence: 93%

Autoantibody profile in cutaneous lupus erythematosus subsets: correlations between various autoantibodies of the same isotype

Kroumpouzos

Tosca

Konstadoulakis

et al. 1994

Acad Dermatol Venereol

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“…Presence of autoantibodies are common in leprosy patients ( 34 ). A key question is whether these autoantibodies are produced because of mimicking epitopes between host protein/s and M. leprae protein/s.…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

et al. 2018

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BackgroundIt has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy.ObjectivesIn this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae.MethodologyOne hundred and sixty-nine leprosy patients and 55 healthy controls (HC) were enrolled in the present study. Levels of anti-myosin antibodies and T-cell responses against myosin were measured by ELISA and lymphoproliferation assay, respectively. Using 2-D gel electrophoresis, western blot and MALDI-TOF/TOF antibody-reactive spots were identified. Three-dimensional structure of mimicking proteins was modeled by online server. B cell epitopes of the proteins were predicted by BCPREDS server 1.0 followed by identification of mimicking epitopes. Mice of inbred BALB/c strain were hyperimmunized with M. leprae soluble antigen (MLSA) and splenocytes and lymph node cells of these animals were adoptively transferred to naïve mice.ResultsHighest level of anti-myosin antibodies was noted in sera of T1R leprosy patients. We observed significantly higher levels of lymphoproliferative response (p < 0.05) with myosin in all types of leprosy patients compared to HC. Further, hyperimmunization of inbred BALB/c strain of female mice and rabbit with MLSA revealed that both hyperimmunized rabbit and mice evoked heightened levels of antibodies against myosin and this autoimmune response could be adoptively transferred from hyperimmunized to naïve mice. Tropomyosin was found to be mimicking with ATP-dependent Clp protease ATP-binding subunit of M. leprae. We found four mimicking epitopes between these sequences.ConclusionThese data suggest that these mimicking proteins tropomyosin and ATP-dependent Clp protease ATP-binding subunit of M. leprae or more precisely mimicking epitopes (four B cell epitopes) might be responsible for extensive tissue damage during type1 reaction in leprosy.

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“…Leprosy, more specifically at the LL pole, is frequently associated with a range of auto-antibody responses, both organ-specific (directed against the thyroid, nerve, testis, and gastric mucosa) and non-specific, such as rheumatoid factor ( Petchclai et al, 1973 ), antineutrophil cytoplasmic autoantibodies (ANCA) ( Medina et al, 1998 ), antinuclear antibodies (ANA) ( Miller et al, 1987 ), and anti-phospholipids ( Arvieux and Hachulla, 2002 ) as well as cryoglobulins ( Bonomo and Dammacco, 1971 ). Other auto-antibodies, like anti-mitochondrial ( Guedes Barbosa et al, 1996 ), anti-actin, anti-myosin ( Kroumpouzos et al, 1993 ), and anti-endothelial cell antibodies ( Dugué et al, 2004 ), have also been reported in patients with leprosy. A conserved mycobacterial membrane protein and mycobacterial ferredoxin-NADP-reductase have been reported to mimic human myelin P0 (a protein that assists in compacting myelin) and it has been suggested that this phenomenon might be responsible for demyelination ( Vardhini et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Corroboration of cross-reactivity between Mycobacterium leprae and hosts’ salivary and cutaneous proteins: A hope for prognostic biomarkers for the pathogenesis of reactions in leprosy

Pathak

Singh²,

Singh

et al. 2022

Front. Microbiol.

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IntroductionImmunological reactions are frequent complications that may occur either before, during, or after treatment and affect 30–50% of leprosy patients. The presence of autoantibodies like rheumatoid factor, antinuclear factor, and antibodies to host collagen, keratin, actin, myosin, endothelial cells, and myelin basic protein (MBP) has been earlier reported in leprosy patients. The purpose of this study was to identify cross-reactive proteins in clinical samples such as saliva and slit skin scrapings (SSS) of leprosy patients which could be utilised as prognostic biomarkers for Type 1 Reaction (T1R) in leprosy.MethodA total of 10 leprosy patients in T1R and 5 healthy volunteers were recruited. The protein was extracted from their SSS and saliva samples, thereafter, isoelectric focusing (IEF) and two-dimensional PAGE were performed to analyse the proteins. Furthermore, the cross-reactivity was identified by western blotting host proteins in gel against purified IgG from Mycobacterium leprae soluble antigen (MLSA)- hyperimmunized rabbit sera, thereafter, cross-reactive proteins were identified by MS/MS. The cross-reactive host proteins were analysed for homologous bacterial proteins and B cell epitopes (BCEs) were predicted by using bioinformatic tools.ResultsA total of five spots of salivary proteins namely S100-A9, 35.3 kDa, and 41.5 kDa proteins, Serpin peptidase inhibitor (clade A), Cystatin SA-III, and four spots of SSS namely 41.4 kDa protein, Alpha-1 antitrypsin, vimentin, and keratin 1, were identified as cross-reactive. Further, a total of 22 BCEs of cross-reactive host proteins were predicted and visualised.DiscussionThis data provides strong evidence of cross-reactivity/molecular mimicry between host and pathogen in leprosy patients with reaction. These BCEs of cross-reactive proteins could be further studied to predict reactions and may be utilised as an early diagnostic biomarker for T1R in leprosy.

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Evaluation of the autoimmune response in leprosy

Cited by 9 publications

References 0 publications

Autoantibody profile in cutaneous lupus erythematosus subsets: correlations between various autoantibodies of the same isotype

Autoantibody profile in cutaneous lupus erythematosus subsets: correlations between various autoantibodies of the same isotype

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

Corroboration of cross-reactivity between Mycobacterium leprae and hosts’ salivary and cutaneous proteins: A hope for prognostic biomarkers for the pathogenesis of reactions in leprosy

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