IgA Response to <scp>ESAT</scp>‐6/<scp>CFP</scp>‐10 and <scp>R</scp>v2031 Antigens Varies in Patients With Culture‐Confirmed Pulmonary Tuberculosis, Healthy <i><scp>M</scp>ycobacterium tuberculosis–</i>Infected and Non‐Infected Individuals in a Tuberculosis Endemic Setting, <scp>E</scp>thiopia

Legesse, Mengistu; Ameni, Gobena; Medhin, Girmay; Mamo, Gezahegne; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; Bjune, Gunnar; Abebe, Fekadu

doi:10.1111/sji.12080

Cited by 31 publications

(30 citation statements)

References 46 publications

(76 reference statements)

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“…However, there is evidence which supports the fact that free ESAT-6 is available for interaction with immune cells during live Mtb infection. As B cells recognize intact protein antigens, recent studies reporting elevated titers of ESAT-6 antibodies in TB patient sera5152, support the existence of free ESAT-6 in extracellular space of tissues during TB infection. Indeed it was shown recently that dendritic cells infected with Mtb release intact Mtb proteins including ESAT-653.…”

Section: Discussionmentioning

confidence: 94%

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

Jung

Wang

et al. 2017

Sci Rep

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As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production. ESAT-6 but not Pam3CSK4 induced IL-6 by TLR2 knockout BMDM. ESAT-6 induced phosphorylation and DNA binding of STAT3 and this was blocked by STAT3 inhibitors but not by rapamycin. STAT3 inhibitors suppressed ESAT-6-induced IL-6 transcription and secretion without affecting cell viability. This was confirmed by silencing STAT3 in macrophages. Blocking neither IL-6Rα/IL-6 nor IL-10 affected ESAT-6-induced STAT3 activation and IL-6 production. Infection of BMDM and human macrophages with Mtb with esat-6 deletion induced diminished STAT3 activation and reduced IL-6 production compared to wild type and esat-6 complemented Mtb strains. Administration of ESAT-6 but not CFP10 induced STAT3 phosphorylation and IL-6 expression in the mouse lungs, consistent with expression of ESAT-6, IL-6 and phosphorylated-STAT3 in Mtb-infected mouse lungs. We conclude that ESAT-6 stimulates macrophage IL-6 production through STAT3 activation.

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Section: Discussionmentioning

confidence: 94%

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

Jung

Wang

et al. 2017

Sci Rep

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“…In the present study, IgA were in part more accurate than their IgG counterparts. In a previous study by Legesse et al ., [26] IgA responses to protein antigens (ESAT-6/CFP-10 and Rv2031) were also found to be more accurate for diagnosis of active TB than IgG responses in TB endemic settings.…”

Section: Discussionmentioning

confidence: 99%

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

et al. 2017

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Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.

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“…Ainda assim, com os resultados obtidos torna-se perceptível a importância da avaliação de outros isótipos de imunoglobulinas (Ig). Em particular a IgA, que foi classificada pelos autores como bastante precisa, conferindo com ensaios anteriores empregando o ELISA em soro de indivíduos adultos (BAUMANN et al, 2014;LEGESSE et al, 2013).…”

Section: Biomarcadores Para Diagnóstico Da Doençaunclassified

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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IgA Response to ESAT‐6/CFP‐10 and Rv2031 Antigens Varies in Patients With Culture‐Confirmed Pulmonary Tuberculosis, Healthy Mycobacterium tuberculosis–Infected and Non‐Infected Individuals in a Tuberculosis Endemic Setting, Ethiopia

Cited by 31 publications

References 46 publications

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

Biomarcadores da tuberculose: uma revisão da literatura.

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