Immunology Dysregulation in Lymphadenitis Tuberculosis : An Observational Study Using Patient' Block Paraffins 2019 Until 2021

NCT05202548 | Completed

• 1 other identifier: 002/AMD-SP2H/LT-MULTIPDPK/LL7
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphadenitis, Tuberculous; Immune Defect

Keywords

Lymphadenitis tuberculosis; C-C Chemokines receptor - 2 (CCR-2); C-C Chemokines ligand - 5 (CCL-5); Cytokines inflammatory

Outcome Measures

Primary Outcomes (1)

• IHC slides

  Histopathology slides stained by immuno-histochemical substrates

  15 November 2021

Study Arms (1)

Lymphadenitis TB

The group study was blocked paraffin from lymphadenitis tuberculosis patient that already confirmed diagnosis histopathological anatomy (PA histopathology)

Other: Immuno-histochemical staining

Interventions

Immuno-histochemical staining OTHER

blocked paraffin that suit with inclusion and exclusion criteria proceed with immuno-histochemical staining to define immune dysregulation in lymphadenitis TB

Lymphadenitis TB

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population in this study was blocked paraffin that diagnosed with lymphadenitis TB by pathologist and confirmed with MPT64 staining

You may qualify if:

• Lymphadenitis TB blocked paraffin that already confirmed by the Pathologist and MPT64 staining

You may not qualify if:

• broken blocked paraffin due to the storage process

Sponsors & Collaborators

• Universitas Katolik Widya Mandala Surabaya: lead
• Indonesia's Ministry of Research and Technology (Ristekdikti/BRIN): collaborator

Study Sites (1)

Vincentius A Paulo Surabaya Hospital

Surabaya, East Java, 60264, Indonesia

Location

Related Publications (1)

• Novita BD, Tjahjono Y, Wijaya S, Theodora I, Erwin F, Halim SW, Hendrawan B, Jaya DK, Tahalele PL. Characterization of chemokine and cytokine expression pattern in tuberculous lymphadenitis patient. Front Immunol. 2022 Nov 10;13:983269. doi: 10.3389/fimmu.2022.983269. eCollection 2022.

  PMID: 36439164 DERIVED

MeSH Terms

Conditions

Tuberculosis, Lymph Node

Condition Hierarchy (Ancestors)

Tuberculosis, Extrapulmonary; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD.,PhD

Study Record Dates

• First Submitted: January 8, 2022
• First Posted: January 21, 2022
• Study Start: May 1, 2021
• Primary Completion: June 25, 2021
• Study Completion: June 25, 2021
• Last Updated: January 21, 2022

Record last verified: 2022-01

Locations

ID (1)