Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins

Talavera-Paulin, Moises; García-Morales, Lázaro; Bp, Ruíz-Sánchez; Ád, Caamal-Ley; Hernández-Solís, Alejandro; Ramírez-Casanova, E; Cícero-Sabido, Raúl; Espitia, Clara; Helguera-Repetto, Addy Cecilia; Ja, González-Y-Merchand; Flores-Mejía, Raúl; Estrada‐Parra, Sergio; Estrada-Garcı́a, Iris; Chacón‐Salinas, Rommel; Wong‐Baeza, Isabel; Serafín‐López, Jeanet

doi:10.5588/ijtld.16.0250

Cited by 4 publications

(3 citation statements)

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“…We encountered a similar phenomenon in this study, which resulted in 'negative' (< 0) ΔOD values for anti-Acr IgM antibodies. This observation was in complete contrast to some of the earlier studies which have shown high levels (OD >1.5) of anti-Acr IgM antibodies in ATB patients as well as healthy contacts [29,32,45,50]. Apart from the demographic differences in study populations, such discrepant results may also occur due to purely technical reasons.…”

Section: Discussioncontrasting

confidence: 98%

“…Further, like us, they had also observed a significant decline in their levels after successful treatment. Some other studies highlighting the diagnostic potential of anti-Acr IgA antibodies have been conducted by Abebe at al [29], Davidow et al [30], Legesse et al [41] and Talavera-Paulin et al [45]. Collectively, these studies emphasize the need to further explore the potential of anti-MtM IgM and anti-Acr IgA antibodies for the discrimination between HCWs and ATB.…”

Section: Discussionmentioning

confidence: 97%

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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: Discussioncontrasting

confidence: 98%

Section: Discussionmentioning

confidence: 97%

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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“…High IgG antibody levels in TB patients have been reported in several studies and are believed to reflect the burden of infection [ 6 , 14 , 15 ]. High IgA levels against certain Mtb antigens have also been reported in patients [ 40 ]. The dominant IgM responses in LTBI have been reported previously by us as well as others.…”

Section: Discussionmentioning

confidence: 99%

Distinct and shared B cell responses of tuberculosis patients and their household contacts

Singh

Kumar²,

Umam³

et al. 2022

PLoS ONE

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This study was aimed at identifying the B cell responses which could distinguish between ‘latent tuberculosis infection (LTBI)’ and active TB disease. Study subjects were smear-positive TB patients (n = 54) and their disease-free household contacts (HHCs, n = 120). The sera were used for determination of antibody levels (ΔOD values) against Mycobacterium tuberculosis membrane (MtM) antigens by ELISA and for visualisation of seroreactive MtM antigens by immunoblotting. B cell subsets in whole blood samples were determined by flow cytometry. In TB sera, levels of IgG antibodies were significantly higher than IgM and IgA whereas IgM and IgA antibody levels were comparable. Conversely, HHC sera had significantly higher IgM antibody levels than IgG and IgA. The ratio of IgM to IgG antibodies in HHCs were also significantly higher than in patients. Immunoblotting revealed that some of the MtM antigens (<10, ~12 and ~25 kDa) reacted with TB as well as HHC sera whereas some other antigens (~16, ~36, ~45 and ~60 kDa) reacted with most of TB and a subset of HHC sera. Frequencies of classical memory B cells (cMBCs, CD19+CD27+) were significantly higher, and of IgG+ cMBCs were significantly lower in HHCs than in patients. Frequencies of IgA+ cMBCs in HHCs and patients were comparable but both were significantly higher than the corresponding frequencies of IgG+ cMBCs. Frequencies of IgA+ atypical MBCs (aMBCs, CD19+CD27-) in HHCs and patients were also comparable and significantly higher than the IgG+ aMBCs. The plasmablast (CD19+CD27++CD38++) frequencies in HHCs and patients were comparable. These results suggest that the IgM/IgG antibody ratio, antibody binding to selected MtM antigens and relative frequencies of MBC subsets could indicate protective or pathogenic immune responses following the primary infection with Mtb. Responses that orchestrate protection leading to a ‘quiescent’ LTBI may provide clues to an effective vaccination strategy against TB.

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Antimicrobial antibodies by phage display: Identification of antibody-based inhibitor against mycobacterium tuberculosis isocitrate lyase

Ch’ng

Schepergerdes

Choong

et al. 2022

Molecular Immunology

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Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins

Abstract: ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

Cited by 4 publications

References 0 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

Distinct and shared B cell responses of tuberculosis patients and their household contacts

Antimicrobial antibodies by phage display: Identification of antibody-based inhibitor against mycobacterium tuberculosis isocitrate lyase

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