Complement component C1q as serum biomarker to detect active tuberculosis

Lubbers, Rosalie; Sutherland, Jayne S.; Goletti, Delia; Verreck, Frank A. W.; Geluk, Annemieke; Ottenhoff, Tom H. M.; Joosten, Simone A.; Trouw, Leendert A.

doi:10.1016/j.molimm.2018.06.149

Cited by 10 publications

(17 citation statements)

References 31 publications

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“…9 Further on analysing publicly available blood gene expression microarray data of TB patients in comparison with latent TB or other lung diseases complement gene C1QC transcripts were observed more than 2 fold higher in TB patients in 78% (7/9) of the studies. 16 C1QC encodes for Cchain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the classical complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains.…”

Section: Discussionmentioning

confidence: 99%

“…10 One of the major limitations of the present study was its limited sample size. Further, previously published data reported a rapid decrease in C1qm RNA expression levels following Anti-tubercular treatment (ATT).Cliff et al 8 reported a decrease in blood C1qC genes after 1 week treatment; Cai et al 10 reported a significant decrease in the expression of the C1qC genes at 3 months of ATT and decrease in C1qC protein in peripheral blood at 6 months; whereas Lubbers et al 16 reported a gradual decrease in protein level until 6 months. Thus, evaluating serum C1qC levels during ATT might have provided much better insight of the biomarker potential of C1qC in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Serum Complement Component 1Q Subcomponent C (C1qC) as a Marker for Tuberculosis

Kumar¹,

Chawla²,

Madigubba³

et al. 2019

jemds

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A B S T R A C T BACKGROUNDDespite several efforts, tuberculosis (TB) continues to be a global concern. For proper management of TB, more sensitive and specific biomarkers for early and accurate diagnosis of TB are still required. Blood based host markers are more appealing as an alternate to sputum-based diagnostics. Thus, in the present study, we evaluated the potential of Serum Complement Component 1 Q Subcomponent C (C1qC) as a marker for tuberculosis. METHODSSerum samples from 84 subjects which included 39 smear positive pulmonary TB patients and 45 controls (Latent TB n=15, Healthy n= 15 and patients with respiratory diseases other than TB n= 15) were collected and Enzyme Linked Immunosorbent Assay was performed to estimate the serum C1qC levels. RESULTSThe mean (±SD) serum C1qC levels in TB, Healthy, Latent TB and patients with respiratory diseases other than TB was found to be 21.80 (±4.39), 13.64 (±1.32), 15.18(±1.29) and 17.31(±1.87) pg/ml respectively. The AUC of serum C1qC to discriminate TB patients from controls was found to be 0.924 (95% CI, 0.869-0.978). At an optimal cut-off value of 16.99 pg/ml, the sensitivity and specificity of serum C1qC to discriminate TB from controls was found to be 84.62% (95% CI, 69.47%-94.14%) and 84.44% (95% CI, 70.54%-93.51%) respectively with a likelihood ratio of 5.44. CONCLUSIONSThe levels of serum C1qC in TB patients was found to be significantly higher than controls. C1qC seems to be a promising marker for the diagnosis and therapeutic monitoring of TB, though further elaborate studies in larger cohorts are required to establish the role for C1qC in the diagnosis and therapeutic monitoring of TB.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Serum Complement Component 1Q Subcomponent C (C1qC) as a Marker for Tuberculosis

Kumar¹,

Chawla²,

Madigubba³

et al. 2019

jemds

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“…We and others have previously described serum C1q as a biomarker of active TB disease 18,19 . In patients with active TB we observed significantly higher levels of serum C1q compared to individuals with latent Mtb infection or individuals with non-mycobacterial pneumonia.…”

Section: Tuberculosis (Tb) Causes 16 Million Deaths Annually Early mentioning

confidence: 99%

Systemic and pulmonary C1q as biomarker of progressive disease in experimental non-human primate tuberculosis

Dijkman

Lubbers

Borggreven

et al. 2020

Sci Rep

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Tuberculosis (TB) causes 1.6 million deaths annually. Early differential diagnosis of active TB infection is essential in optimizing treatment and reducing TB mortality, but is hampered by a lack of accurate and accessible diagnostics. Previously, we reported on complement component C1q, measured in serum by ELISA, as a candidate biomarker for active tuberculosis. In this work we further examine the dynamics of C1q as a marker of progressive TB disease in non-human primates (NHP). We assessed systemic and pulmonary C1q levels after experimental infection using high or low single dose as well as repeated limiting dose Mycobacterium tuberculosis (Mtb) challenge of macaques. We show that increasing C1q levels, either peripherally or locally, correlate with progressive TB disease, assessed by PET-CT imaging or post-mortem evaluation. Upregulation of C1q did not precede detection of Mtb infection by a conventional interferon-gamma release assay, confirming its association with disease progression. Finally, pulmonary vaccination with Bacillus Calmette Guérin also increased local production of C1q, which might contribute to the generation of pulmonary protective immunity. Our data demonstrate that NHP modelling of TB can be utilized to study the role of C1q as a liquid biomarker in TB protection and disease, complementing findings in TB patients.

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“…O comportamento da proteína C1q do Sistema Complemento durante PTB e LTBI foi analisado em um estudo com amostras intercontinentais de regiões endêmicas e não endêmicas da TB, também envolvendo pacientes com hanseníase, sarcoidose e pneumonia -visto que se trata de um biomarcador inflamatório bastante generalista que requer maior validação. A partir de uma análise combinada envolvendo todos os pacientes TB, grupos controle, LTBI e os pacientes tratados com sucesso o trabalho pode constatar que há um aumento significativo da C1q na PTB (p< 0.001) (LUBBERS et al, 2018).…”

Section: Biomarcadores Para Diagnóstico Da Doençaunclassified

“…Ambas seriam proteínas com atividade no sistema complemento, levando a crer que os níveis reduzidos possam ser devido a atenuação das ativações constantes do complemento, sendo aliviado pela conclusão da fase ativa da inflamação (WANG et al, 2018). Proteínas do complemento são estudadas na literatura da tuberculose (CAI et al, 2014;LUBBERS et al, 2018;SENBAGAVALLI et al, 2011), a FCN2 em específico apresenta alguns estudos com determinados pontos conflitantes, especialmente em relação ao impacto de seus genótipos na infecção (CHALMERS et al, 2015;LUO et al, 2013;XU et al, 2015).…”

Section: Biomarcadores Para Monitoramento Da Terapia E Curaunclassified

Biomarcadores da tuberculose: uma revisão da literatura.

Souza

Hermes

2019

R. Eletr. Cient. da Uergs

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A tuberculose é uma infecção micobacteriana comumente causada pelo agente etiológico Mycobacterium tuberculosis, podendo também ser desencadeada por outras bactérias do gênero Mycobacterium. Ainda que bem documentada, mais de um século após sua descoberta, situa-se como a doença infecciosa que mais mata no mundo. Configura-se também problema socioeconômico importante, atingindo em especial as camadas mais pobres da população e comprometendo seriamente sua capacidade produtiva. Os métodos diagnósticos tradicionais para a doença consistem da baciloscopia e cultura, recentemente adotando os testes moleculares rápidos, todos com limitações significativas, como a incapacidade de discriminar entre casos de tuberculose ativa e latente, sensibilidade inconsistente e incapacidade de oferecer prognósticos. A presente revisão da literatura procurou elucidar os atuais avanços na pesquisa de biomarcadores da infecção nos últimos 5 anos com o emprego da metodologia ELISA. Foram verificadas e comparadas evidências apresentadas pelos estudos e as performances diagnósticas alcançadas em cada contexto. Constatou-se uma evidente heterogeneidade nas respostas imunológicas entre populações e indivíduos, provável fruto da diversidade genética do patógeno que possui linhagens intercontinentais e regionais, bem como diferenças particulares nas expressões de alguns biomarcadores, seja por variáveis genéticas ou mesmo outras doenças de base; a homologia dos antígenos pesquisados com outras espécies de bactérias também foi uma problemática. Fica claro que questões genéticas particulares de populações e do próprio agente infeccioso precisam ser melhor consideradas nesses estudos, a fim de alcançar um perfil sorológico suficientemente sensível e específico para triagem clínica e diagnóstico destes pacientes.

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Complement component C1q as serum biomarker to detect active tuberculosis

Cited by 10 publications

References 31 publications

Evaluation of Serum Complement Component 1Q Subcomponent C (C1qC) as a Marker for Tuberculosis

Evaluation of Serum Complement Component 1Q Subcomponent C (C1qC) as a Marker for Tuberculosis

Systemic and pulmonary C1q as biomarker of progressive disease in experimental non-human primate tuberculosis

Biomarcadores da tuberculose: uma revisão da literatura.

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