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 language | English |
|---|---|
| Article number | 2427 |
| Journal | Frontiers in Immunology |
| Volume | 9 |
| Issue number | OCT |
| DOIs | |
| Publication status | Published - Oct 23 2018 |
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Keywords
- Blood
- C1q
- Complement
- Infection
- Innate immunity
- Mycobacterium
- Tuberculosis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
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.
PY - 2018/10/23
Y1 - 2018/10/23
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.
AB - 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.
KW - Blood
KW - C1q
KW - Complement
KW - Infection
KW - Innate immunity
KW - Mycobacterium
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85055789492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055789492&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.02427
DO - 10.3389/fimmu.2018.02427
M3 - Article
AN - SCOPUS:85055789492
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - OCT
M1 - 2427
ER -