Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05202548 |
| Other study ID # |
002/AMD-SP2H/LT-MULTIPDPK/LL7 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2021 |
| Est. completion date |
June 25, 2021 |
Study information
| Verified date |
January 2022 |
| Source |
Universitas Katolik Widya Mandala Surabaya |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Mycobacterium tuberculosis (M. tuberculosis) infection is still a problem that cannot be
overcome in Indonesia. In 2018 the number of tuberculosis (TB) sufferers in Indonesia reached
more than 850/100,000 population, an increase around 20% from the previous year's incidence.
One of the highest number of cases is in East Java Province, which is 38% of the total number
of new TB cases in Indonesia.
Extrapulmonary tuberculosis (EPTB) according to WHO classification criteria is an M.
tuberculosis infection that occurs in tissues and organs outside the lung parenchyma. The
incidence rate in Indonesia reaches 1-5% of the incidence of TB thus EPTB may often be
forgotten. However, the diagnosis, therapy and monitoring post treatment in EPTB remains
difficult to do.
The focus of this research is tuberculous lymphadenitis (TB), due to 50% of EPTB cases in
Indonesia was lymphadenitis TB. The risk factors for EPTB are immunocompromised conditions,
such as HIV infection or comorbid conditions such as chronic kidney disease (CKD) and
diabetes mellitus, but the mechanism of EPTB homing is still unclear. The mechanism of EPTB
homing, especially TB lymphadenitis, really needs to be known for the development of
diagnostics and therapy as well as preventing the occurrence of TB lymphadenitis.
The importance of this research is to obtain compounds from the human immune response that
can be developed as diagnostic markers and therapeutic targets for tuberculosis infection,
especially TB lymphadenitis. Activated macrophages containing M. tuberculosis are carried by
lymph flow to lymph nodes, where there is deposition of antigen-antibody complexes which then
activate CC Chemokine Receptor-2 (CCR2) on lymphocytes, which are the primary receptors for
Chemokine (CC motif) ligands ( CCL)-8 and CCL5, proteins expressed on macrophages containing
M. tuberculosis. Activation of CCR2 increases the production of IL-10(10). IL-10 has been
responsible for decreasing the secretion of TNF-, IFN-γ, and IL-1β (11). IFN-γ affects the
process of M. tuberculosis elimination and the success of TB therapy, so that IL-10 is
responsible for the failure of macrophages to eliminate M. tuberculosis. IL-10 also binds to
Signal Transducer and Activator of Transcription 3 (STAT3) and STAT3 increases the release of
Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 interferes with IFN-γ signaling for CCR2
recognition of M. tuberculosis-containing macrophages. On the other hand, the mechanism of T
lymphocytes and macrophages that activate pro-inflammatory mediators (TNF-, IFN-γ, and IL-1β)
and the association of IL-10 activation on STAT3, SOCS3 and CCR2 expression in the incidence
of EPTB, especially TB lymphadenitis without TB infection remains unknown.
Description:
Mycobacterium tuberculosis (M. tuberculosis) infection is still a problem that cannot be
overcome in Indonesia. In 2018 the number of tuberculosis (TB) sufferers in Indonesia reached
more than 850/100,000 population, an increase around 20% from the previous year's incidence.
One of the highest number of cases is in East Java Province, which is 38% of the total number
of new TB cases in Indonesia.
Extrapulmonary tuberculosis (EPTB) according to WHO classification criteria is an M.
tuberculosis infection that occurs in tissues and organs outside the lung parenchyma. The
incidence rate in Indonesia reaches 1-5% of the incidence of TB thus EPTB may often be
forgotten. However, the diagnosis, therapy and monitoring post treatment in EPTB remains
difficult to do.
The focus of this research is tuberculous lymphadenitis (TB), due to 50% of EPTB cases in
Indonesia was lymphadenitis TB. The risk factors for EPTB are immunocompromised conditions,
such as HIV infection or comorbid conditions such as chronic kidney disease (CKD) and
diabetes mellitus, but the mechanism of EPTB homing is still unclear. The mechanism of EPTB
homing, especially TB lymphadenitis, really needs to be known for the development of
diagnostics and therapy as well as preventing the occurrence of TB lymphadenitis.
The importance of this research is to obtain compounds from the human immune response that
can be developed as diagnostic markers and therapeutic targets for tuberculosis infection,
especially TB lymphadenitis. Activated macrophages containing M. tuberculosis are carried by
lymph flow to lymph nodes, where there is deposition of antigen-antibody complexes which then
activate CC Chemokine Receptor-2 (CCR2) on lymphocytes, which are the primary receptors for
Chemokine (CC motif) ligands ( CCL)-8 and CCL5, proteins expressed on macrophages containing
M. tuberculosis. Activation of CCR2 increases the production of IL-10(10). IL-10 has been
responsible for decreasing the secretion of TNF-, IFN-γ, and IL-1β (11). IFN-γ affects the
process of M. tuberculosis elimination and the success of TB therapy, so that IL-10 is
responsible for the failure of macrophages to eliminate M. tuberculosis. IL-10 also binds to
Signal Transducer and Activator of Transcription 3 (STAT3) and STAT3 increases the release of
Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 interferes with IFN-γ signaling for CCR2
recognition of M. tuberculosis-containing macrophages. On the other hand, the mechanism of T
lymphocytes and macrophages that activate pro-inflammatory mediators (TNF-, IFN-γ, and IL-1β)
and the association of IL-10 activation on STAT3, SOCS3 and CCR2 expression in the incidence
of EPTB, especially TB lymphadenitis without TB infection remains unknown.
In this study, Lymphadenitis TB paraffin blocks from patients were collected and screened for
immunological responses that TB patients have potential as targets for diagnosis and therapy.
The paraffin block samples came from the Anatomical Pathology Laboratory of St. Catholic
Hospital. Vincentius A Paulo (RKZ) Surabaya. Existing samples were taken and performed
immuno-histochemical (IHC) to define theimmune dysregulation in TB lymphadenitis.
