Complement component C1q as serum biomarker to detect active tuberculosis

Rosalie Lubbers, Jayne S. Sutherland, Delia Goletti, Roelof A. De Paus, Coline H.M. Van Moorsel, Marcel Veltkamp, Stefan M.T. Vestjens, Willem J.W. Bos, Linda Petrone, Franca Del Nonno, Ingeborg M. Bajema, Karin Dijkman, Frank A.W. Verreck, Gerhard Walzl, Kyra A. Gelderman, Geert H. Groeneveld, Annemieke Geluk, Tom H.M. Ottenhoff, Simone A. Joosten, Leendert A. Trouw

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

Original languageEnglish
Article number2427
JournalFrontiers in Immunology
Volume9
Issue numberOCT
DOIs
Publication statusPublished - Oct 23 2018

Fingerprint

Complement C1q
Tuberculosis
Biomarkers
Serum
Latent Tuberculosis
Leprosy
Mycobacterium
Sarcoidosis
Infection
Pneumonia
Therapeutic Irrigation
Genetic Predisposition to Disease
Mycobacterium bovis
Mycobacterium tuberculosis
Primates
Lung Diseases
Area Under Curve

Keywords

  • Blood
  • C1q
  • Complement
  • Infection
  • Innate immunity
  • Mycobacterium
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lubbers, R., Sutherland, J. S., Goletti, D., De Paus, R. A., Van Moorsel, C. H. M., Veltkamp, M., ... Trouw, L. A. (2018). Complement component C1q as serum biomarker to detect active tuberculosis. Frontiers in Immunology, 9(OCT), [2427]. https://doi.org/10.3389/fimmu.2018.02427

Complement component C1q as serum biomarker to detect active tuberculosis. / Lubbers, Rosalie; Sutherland, Jayne S.; Goletti, Delia; De Paus, Roelof A.; Van Moorsel, Coline H.M.; Veltkamp, Marcel; Vestjens, Stefan M.T.; Bos, Willem J.W.; Petrone, Linda; Del Nonno, Franca; Bajema, Ingeborg M.; Dijkman, Karin; Verreck, Frank A.W.; Walzl, Gerhard; Gelderman, Kyra A.; Groeneveld, Geert H.; Geluk, Annemieke; Ottenhoff, Tom H.M.; Joosten, Simone A.; Trouw, Leendert A.

In: Frontiers in Immunology, Vol. 9, No. OCT, 2427, 23.10.2018.

Research output: Contribution to journalArticle

Lubbers, R, Sutherland, JS, Goletti, D, De Paus, RA, Van Moorsel, CHM, Veltkamp, M, Vestjens, SMT, Bos, WJW, Petrone, L, Del Nonno, F, Bajema, IM, Dijkman, K, Verreck, FAW, Walzl, G, Gelderman, KA, Groeneveld, GH, Geluk, A, Ottenhoff, THM, Joosten, SA & Trouw, LA 2018, 'Complement component C1q as serum biomarker to detect active tuberculosis', Frontiers in Immunology, vol. 9, no. OCT, 2427. https://doi.org/10.3389/fimmu.2018.02427
Lubbers R, Sutherland JS, Goletti D, De Paus RA, Van Moorsel CHM, Veltkamp M et al. Complement component C1q as serum biomarker to detect active tuberculosis. Frontiers in Immunology. 2018 Oct 23;9(OCT). 2427. https://doi.org/10.3389/fimmu.2018.02427
Lubbers, Rosalie ; Sutherland, Jayne S. ; Goletti, Delia ; De Paus, Roelof A. ; Van Moorsel, Coline H.M. ; Veltkamp, Marcel ; Vestjens, Stefan M.T. ; Bos, Willem J.W. ; Petrone, Linda ; Del Nonno, Franca ; Bajema, Ingeborg M. ; Dijkman, Karin ; Verreck, Frank A.W. ; Walzl, Gerhard ; Gelderman, Kyra A. ; Groeneveld, Geert H. ; Geluk, Annemieke ; Ottenhoff, Tom H.M. ; Joosten, Simone A. ; Trouw, Leendert A. / Complement component C1q as serum biomarker to detect active tuberculosis. In: Frontiers in Immunology. 2018 ; Vol. 9, No. OCT.
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abstract = "Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.",
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T1 - Complement component C1q as serum biomarker to detect active tuberculosis

AU - Lubbers, Rosalie

AU - Sutherland, Jayne S.

AU - Goletti, Delia

AU - De Paus, Roelof A.

AU - Van Moorsel, Coline H.M.

AU - Veltkamp, Marcel

AU - Vestjens, Stefan M.T.

AU - Bos, Willem J.W.

AU - Petrone, Linda

AU - Del Nonno, Franca

AU - Bajema, Ingeborg M.

AU - Dijkman, Karin

AU - Verreck, Frank A.W.

AU - Walzl, Gerhard

AU - Gelderman, Kyra A.

AU - Groeneveld, Geert H.

AU - Geluk, Annemieke

AU - Ottenhoff, Tom H.M.

AU - Joosten, Simone A.

AU - Trouw, Leendert A.

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N2 - Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

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