Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes

Senbagavalli, Prakash; Hilda, J. Nancy; Ramanathan, V. D.; Kumaraswami, V.; Nutman, Thomas B.; Babu, Subash

doi:10.1128/cvi.00437-12

Cited by 8 publications

(10 citation statements)

References 34 publications

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“…In our present study, we observed almost 5 fold higher ICs in human PKDL subjects. Aberrant glycosylation of proteins in ICs often play important role in pathogenesis of various disease conditions like SLE, Rheumatoid Arthritis and Cancer [ 49 – 52 ]. Recently, CICs has also been identified to play active role in Leishmania infection [ 22 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India

Jaiswal¹,

Datta²,

Sardar

et al. 2018

PLoS ONE

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BackgroundPost Kala Azar Dermal Leishmaniasis (PKDL) occurs as dermal consequence of previous Visceral Leishmaniasis (VL) infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and prognostic assay of PKDL are required.ObjectivePreviously, glycoproteins (9-OAcSA) have been reported as promising biomarkers of Indian VL patients. However, till date, the status of glycans in Indian PKDL patients remains unexplored. Accordingly, in this study, the glyco-profile of PKDL Circulating Immune Complexes (CICs) as compared to other cross diseases like Vitiligo and Leprosyhas been investigated. Further, a novel Glyco CIC assay has been developed for efficient Indian PKDL patient diagnosis.Methods/principal findingIn the present study, 90 PKDL patients were enrolled from 3 VL endemic districts of West Bengal during 2015–16. Glycosylation profile of isolated CICs from sera of PKDL patients were initially analyzed through gradient SDS gel electrophoresis followed by PAS silver double staining, which revealed the presence of several glycan rich PKDL specific proteins of varying molecular weights. To further characterize the glyco-profile of acid dissociated affinity purified immuno-reactive antigens present in the CICs, glycosylation was demonstrated in these purified CIC antigens by DIG glycan differentiation kit with or without glycosidase as well as neuraminidase treatment. Diagnostic evaluation of the newly developed colorimetric Glyco CIC assay through Receiver Operating Characteristic (ROC) curve analysis revealed excellent (0.99) AUC value as compared to other conventional serodiagnostic assays like PEG CIC, Parasite ELISA (IgG and IgM). Additionally, longitudinal monitoring of 18 PKDL patients further revealed its good prognostic utility.ConclusionThese results highlight the glycosylation status of CICs among Indian PKDL patients present in all the studied endemic districts of West Bengal. These PKDL biomarkers were completely absent in cross diseases like Vitiligo and Leprosy. Further, the newly developed Glyco CIC assay had an improved sensitivity of 95.6%, specificity of 99.3%, NPV of 97.1% and PPV of 98.9%.

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Section: Discussionmentioning

confidence: 99%

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India

Jaiswal¹,

Datta²,

Sardar

et al. 2018

PLoS ONE

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“…Hypergamma-globulinemia was also reported in some systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis, lymphogranuloma venereum, a chronic liver disease like cirrhosis, angioimmunoblastic lymphadenopathy and some classes of lymphomas [ 56 ]. However, infectious diseases like tuberculosis, malaria, filarial, leprosy, influenza are known for comparatively lower expression of CICs [ 24 , 31 , 57 , 58 ]. Asthma was also observed with higher expression of CICs.…”

Section: Discussionmentioning

confidence: 99%

Identification of Leishmania donovani antigen in circulating immune complexes of visceral leishmaniasis subjects for diagnosis

et al. 2017

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The unreliability of most of the existing antibody-based diagnostic kits to discriminate between active and treated VL cases, relapse situation and reinfection are a major hurdle in controlling the cases of Kala-azar in an endemic area. An antigen targeted diagnostic approaches can be an attractive strategy to overcome these problems. Hence, this study was focused on identifying the Leishmania antigens, lies in circulating immune complex (CICs), can be used for diagnostic as well as prognostic purposes. The present study was conducted on peripheral blood samples of 115 human subjects, based on isolation of CICs. The SDS-PAGE patterns showed an up-regulated expression of 55 kDa and 23 kDa fractions in an antigens obtained from CICs of all clinical and parasitologically proven untreated visceral leishmaniasis patients before treatment (VL-BT), which ensured absolute sensitivity. However, light expressions of these bands were observed in some VL treated cases. To ascertain the prognostic value, 2D expression profiles of circulating antigens were carried out, which revealed 3 upregulated and 12 induced immunoreactive spots. Out of these, ten prominent spots were excised and subjected for enzymatic digestion to generate peptides. Mass spectrometry (MS) analysis successfully explored 20 peptides derived from kinase, kinesin, acetyl Co-A carboxylase, dynein heavy chains (cytoplasmic and axonemal/flagellar), 60S ribosomal protein, nucleoporin protein, RNA polymeraseII, protease gp63, tubulin, DNA polymerase epsilon subunit, GTP-binding protein and tyrosyl-methionyl t-RNA synthetase-like protein and 19 hypothetical protein of unknown function. Presence of L. donovani proteins in circulating antigens were further validated using anti-Ld actin and anti-α tubulin antibody. Besides, MS derived peptides confirmed its reactivity with patients' sera. Therefore, these shortlisted potential antigens can be explored as antigen-based diagnostic as well as prognostic kit.

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“…A recent study monitoring the transition of latent TB to active TB also reported activation of complement pathway genes and increased levels of antigen/antibody complexes in the early stage of Human Immunodeficiency Virus (HIV) associated TB 6 . An earlier study also reported the possible role of CIC's in generating an immune response and regulating variety of immune complexes mediated inflammatory events in tuberculosis 7 . The clinical role of the CIC present in the serum of tuberculosis patients is still unclear, although several studies have tried to demonstrate the specificity of these immune complexes.…”

Section: Introductionmentioning

confidence: 92%

“…for various circulating immune complex associated diseases. Presence of IC's is established in both circulation and in tissues in TB 7 . Thus, in the present study, we made an attempt to explore the proteomic profile of circulating immune complexes from tuberculosis patients in comparison with latent TB and healthy controls.…”

Section: Validation Of Complement C1q Subcomponent Subunit C (C1qc_humentioning

confidence: 99%

Proteomic Analysis of Circulating Immune Complexes from Tuberculosis Patients

Kumar¹,

Chawla²,

Thakur³

et al. 2019

J Pure Appl Microbiol

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Circulating immune complexes (CIC's) are associated with disease progression in Tuberculosis (TB) though their role in pathogenesis is still unclear. Hence the present study was undertaken to identify proteins of diagnostic potential in tuberculosis by proteomic profiling of CIC's. Serum samples from tuberculosis patients (n=28), latent TB (n=10) and healthy (n=15) individuals were collected and CIC's levels were estimated by ELISA. CIC's were isolated by 7% Polyethylene Glycol precipitation and were subjected to proteomic analysis. Bioinformatic analysis and functional annotation of identified proteins was performed using Mascot search engine and PANTHER respectively. Identified protein was validated by ELISA. Statistical analysis was performed with SPSS version 16 and Graph pad prism 5. The mean CIC concentration in TB, latent TB and healthy individuals was found to be 38.23±11.45, 24.43±15.09, and 8.61±2.47µg/ml respectively. A total of 74, 48 and 60 proteins were identified in CIC's from of TB, latent TB and healthy individuals respectively. Among identified proteins the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of C1qC to distinguishing TB patients from controls (with respect to both latent TB and healthy controls) was found to be 87.18% , 93.33%, 94.44%, 84.85% and 89.86% respectively. Our exploratory analysis suggests that immune-complex based assays might provide better alternate to invasive diagnostic techniques especially in diagnosis of extra pulmonary TB. However, further elaborate studies are required.

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Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes

Cited by 8 publications

References 34 publications

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India

Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India

Identification of Leishmania donovani antigen in circulating immune complexes of visceral leishmaniasis subjects for diagnosis

Proteomic Analysis of Circulating Immune Complexes from Tuberculosis Patients

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