Defective Solubilization of Immune Complexes and Activation of the Complement System in Patients with Pulmonary Tuberculosis

Senbagavalli, Prakash; Geetha, S.; Venkatesan, P; Ramanathan, V. D.

doi:10.1007/s10875-009-9301-0

Cited by 6 publications

(4 citation statements)

References 8 publications

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“…The causes of this elevated type I IFN expression in SLE are likely deposition of ICs triggering IFNα production by plasmacytoid dendritic cells through Fc gamma receptors [19]. Elevated levels of IC accompanied by defective IC solubilization has also been documented in serum of TB patients [20] and may account, at least in part, for the similarities in gene signatures observed in both diseases. Reduced solubilization of IC also has a well-known pathological manifestation in leprosy, notably during malignant stages [21], which is caused by the mycobacterial pathogen M. leprae .…”

Section: Discussionmentioning

confidence: 98%

Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis

et al. 2011

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Tuberculosis remains a major health threat and its control depends on improved measures of prevention, diagnosis and treatment. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. Such profiles also reveal fundamental biological mechanisms associated with the pathology of the disease. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These analyses were employed for identification of new disease-associated gene signatures, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed. Functional gene clusters of immunoregulatory interactions involving the JAK-STAT pathway; sensing of microbial patterns by Toll-like receptors and IFN-signaling provide detailed insights into the dysregulation of critical immune processes in TB, involving active expression of both pro-inflammatory and immunoregulatory systems. We conclude that transcriptomics (i) provides a robust system for identification and validation of biosignatures for TB and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis.

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Section: Discussionmentioning

confidence: 98%

Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis

et al. 2011

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“…Apart from a reduction in lymphocyte numbers, defects in T‐cell function and cytokine signaling have demonstrated the patients’ susceptibility to TB. The levels of C3 are usually elevated in TB infection 12 . Conversely, decreased C3 was found in lupus mimickers of Cases 2, 3 and 6.…”

Section: Discussionmentioning

confidence: 88%

“…The levels of C3 are usually elevated in TB infection. 12 Conversely, decreased C3 was found in lupus mimickers of Cases 2, 3 and 6. Although the exact mechanism is not clear, the same phenomenon was found in a Warao population with latent or active TB infection.…”

Section: Discussionmentioning

confidence: 93%

Tuberculosis mimicking the onset of systemic lupus erythematosus flare: Case based review

et al. 2023

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Aim To analyze the clinical features of lupus‐like tuberculosis (TB). Methods Three cases of TB imitating systemic lupus erythematosus (SLE) flare were collected in our hospital. Based on literature review, there are only 3 reports of TB resembling lupus flare rather than SLE per se. Results The 3 cases of lupus mimickers, with a mean age of 30.3 years, ranging from 27 to 32 years, had atypical features of SLE, namely no typical butterfly erythema, lupus hair, alopecia or proteinuria, similar to the patients reported in the 3 previously mentioned studies. Emergence of different autoantibodies like anti‐nuclear antibodies, anti‐double‐stranded DNA, anti‐nucleosome antibodies, and anti‐histone antibodies could occur in TB, mostly as an epiphenomenon. In patients with specific serological anti‐Sm and hypocomplementemia, active TB cannot be easily ruled out. The presence of autoantibodies neither altered the clinical manifestations and radiographic findings of active TB, nor were detectable after infections are resolved. The resistance of the SLE manifestations to the steroid and immunosuppressive treatment suggests the contribution of an infectious disease. Conclusion TB stimulated the production of autoantibodies, with shared affinity for mycobacteria and human antigens, which may have led to lupus mimickers.

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“…The late relapse in ICs levels on day 60 could be explained by the dynamics of memory B cell and plasma cell differentiation, which can secrete specific antibodies and survive without antigenic stimulation [ 38 , 39 ]. Alterations leading to constant activation of the complement system may play a role as well, and other authors have shown that, in active pulmonary TB patients, there are also abnormalities in the solubilization of ICs leading to persistent aseptic complement activation [ 40 ]. Moreover, ICs may be formed in situ in the endothelium by specific antibodies towards endothelial molecules, which react by molecular mimicry with cell wall Mtb antigens [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model

Pérez-Noriega

Salinas-Lara

Sánchez-Garibay

et al. 2023

IJMS

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Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.

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Defective Solubilization of Immune Complexes and Activation of the Complement System in Patients with Pulmonary Tuberculosis

Cited by 6 publications

References 8 publications

Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis

Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis

Tuberculosis mimicking the onset of systemic lupus erythematosus flare: Case based review

Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model

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