Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis

Senoputra, Muhammad Andrian; Shiratori, Beata; Hasibuan, Fakhrial Mirwan; Koesoemadinata, Raspati C; Apriani, Lika; Ashino, Yugo; Ono, Kenji; Oda, Tetsuya; Matsumoto, Makoto; Suzuki, Yasuhiko; Alisjahbana, Bachti; Hattori, Toshio

doi:10.1016/j.diagmicrobio.2015.07.021

Cited by 13 publications

(13 citation statements)

References 34 publications

(43 reference statements)

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“…Any prior comparable study on anti-MtM IgG antibodies is not available, whereas available studies on the anti-Acr IgG antibodies have reported equivocal findings. According to some, their levels are low in ATB and high in LTBI [24,28,30] and, according to some others, these levels are high in ATB and low in LTBI [21,25,29,41]. While demographic differences in study populations could have led to such diverse results, differences in antibody assay protocols (discussed below) may also have contributed to it.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to active TB disease, persons with LTBI have shown a stronger T cell response to Acr [21][22][23] which was not influenced by BCG vaccination [23]. High levels of anti-Acr antibodies have been reported in TB patients and their contacts [21,24,25], HCWs exposed to Mtb [26] and cerebrospinal fluid of patients with tuberculous meningitis [27]. Conversely, some studies have found lower antibody levels in active than in inactive or latent TB [28].…”

Section: Introductionmentioning

confidence: 99%

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Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

et al. 2020

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Changes in expression of membrane antigens may accompany the transition of Mycobacterium tuberculosis (Mtb) from 'dormant' to 'active' states. We have determined whether antibody and T cell responses to Mtb membrane (MtM)-associated antigens, especially the latency-induced protein alpha crystallin (Acr), can discriminate between latent tuberculosis infection (LTBI) and active TB (ATB) disease. Study subjects comprised a previously described cohort of healthcare workers (HCWs, n = 43) and smear-positive ATB patients (n = 10). HCWs were further categorized as occupational contacts (OC, n = 30), household contacts of TB (HC, n = 8) and cured TB (CTB, n = 5). Levels (ΔOD) of serum antibody isotypes (IgG, IgA and IgM) were determined by ELISA and blood T cell proliferative responses were determined by flow cytometry using Ki67 protein as marker for DNA synthesis. Antibodies to MtM and Acr were predominantly IgG and their levels in HCWs and ATB did not differ significantly. However, HCWs showed a significantly higher level of anti-MtM IgM and a significantly lower level of anti-Acr IgA antibodies than the ATB patients. Also, a larger proportion of HCWs showed a high (>1) ΔOD Acr /ΔOD MtM ratio for IgG. HCWs also showed a higher, though not significantly different from ATB, avidity of anti-MtM (IgG) antibodies. A higher proportion of HCWs (35% of OC, 62.5% of HC and 20% of CTB), compared with ATB (10%) showed a positive T cell response to Acr along with significant difference (P <0.05) between HC and ATB. A significant correlation (r = 0.60, P <0.0001) was noted between T cell responses of HCWs towards Acr and MtM (reported earlier by us) and both responses tended to decline with rising exposure to the infection. Even so, positive responses to Acr (38.5%) were significantly lower than to MtM (92%). Neither antibody nor T cell responses to either antigen appeared affected by BCG vaccination or reactivity to tuberculin. Results of the study suggest that the levels of IgM antibodies to MtM, IgA antibodies to Acr and

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

et al. 2020

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“…The LTBI group comprised subjects with documented exposure to persons with confirmed TB and positive responses to a tuberculin skin test or INF‐γ release assay (QuantiFERON‐TB Gold In‐Tube test, Cellestis, Chadstone, Vic, Australia) in the absence of clinical or radiographic evidence of TB. The subjects’ medical histories, physical and laboratory examination results were obtained as described previously . HCs had no TB‐related symptoms and their tuberculin skin tests, INF‐γ release assays and radiography findings were negative.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of matricellular proteins in systemic and local immune response to Mycobacterium tuberculosis infection

Hasibuan

Shiratori

Senoputra

et al. 2015

Microbiology and Immunology

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Matricellular proteins such as osteopontin (OPN), galectin-9 (Gal-9), and tenascin-C (TN-C) are expressed not only under normal physiological conditions, but also during infection, inflammation and tumorigenesis. Plasma concentrations of matricellular proteins were studied to determine their diagnostic value as potential markers of tuberculosis (TB) activity. It was found that concentrations of OPN and TN-C were higher in patients with active TB than in healthy controls and individuals with latent infection. Moreover, LTBI patients had higher concentrations of OPN than did healthy controls. Gal-9 concentrations did not differ significantly between groups. Concentrations of matricellular proteins were higher in pleural fluid than in the plasma of patients with TB. Expression of matricellular proteins was also investigated in TB granulomas and other granulomatous diseases. Positive OPN and Gal-9 staining was observed in TB and sarcoidosis granulomas, but not in Crohn disease granulomas. The fibrotic ring around granulomas stained positive for TN-C in TB and sarcoidosis, but not in Crohn disease. Of the three matricellular proteins studied, OPN and TN-C may serve as reliable plasma markers for monitoring TB activity, whereas Gal-9 seems to be expressed more at the site of infection than in the systemic circulation.

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“…This interest in humoral immunity in Mtb is evidenced by a mounting number of studies that have identified specific antibody targets, and structural or functional differences that are observed during different TB disease states (26)(27)(28)(29)(30). For example, while Mtb-specific IgG titers alone have been insufficient in distinguishing between latent and active TB, refinement of these correlates using additional isotypes, subclasses, and other Fc modifications are underway (see Figure 1) (31)(32)(33)(34)(35). Moreover, incorporating data including multiple instead of single Mtb antigens as well as Fab affinity and avidity to Mtb targets may improve sensitivity and specificity (36)(37)(38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis

Abstract: Background

Cited by 13 publications

References 34 publications

Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

Evaluation of matricellular proteins in systemic and local immune response to Mycobacterium tuberculosis infection

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

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