Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease

Quinn, Carson M; Poplin, Victoria; Kasibante, John; Yuquimpo, Kyle; Gakuru, Jane; Cresswell, Fiona V; Bahr, Nathan C

doi:10.3390/life10110262

Cited by 39 publications

(52 citation statements)

References 176 publications

(306 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…"s Notably, the overwhelming complexity of TB-IRIS immunopathogenesis impedes the attainment of accurate predictive and diagnostic methods, thus hindering appropriate patient care and disease management. Currently, a TB-IRIS diagnosis is mainly based on clinical presentation and the initial response of the underlying TB infection to ATT, with a paradoxical deterioration after ART initiation determine from both clinical assessment and imaging methods (such as chest X ray and computed tomography) (23). Therefore, major efforts have been devoted to the identification of prediction and diagnostic biomarkers to enhance TB-IRIS management strategies.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

et al. 2021

View full text Add to dashboard Cite

Most persons living with HIV (PLWH) experience a significant restoration of their immunity associated with successful inhibition of viral replication after antiretroviral therapy (ART) initiation. Nevertheless, with the robust quantitative and qualitative restoration of CD4+ T-lymphocytes, a fraction of patients co-infected with tuberculosis develop immune reconstitution inflammatory syndrome (TB-IRIS), a dysregulated inflammatory response that can be associated with significant tissue damage. Several studies underscored the role of adaptive immune cells in IRIS pathogenesis, but to what degree T lymphocyte activation contributes to TB-IRIS development remains largely elusive. Here, we sought to dissect the phenotypic landscape of T lymphocyte activation in PLWH coinfected with TB inititating ART, focusing on characterization of the profiles linked to development of TB-IRIS. We confirmed previous observations demonstrating that TB-IRIS individuals display pronounced CD4+ lymphopenia prior to ART initiation. Additionally, we found an ART-induced increase in T lymphocyte activation, proliferation and cytotoxicity among TB-IRIS patients. Importantly, we demonstrate that TB-IRIS subjects display higher frequencies of cytotoxic CD8+ T lymphocytes which is not affected by ART. Moreover, These patients exhibit higher levels of activated (HLA-DR+) and profilerative (Ki-67+) CD4+ T cells after ART commencenment than their Non-IRIS counterparts. Our network analysis reveal significant negative correlations between Total CD4+ T cells counts and the frequencies of Cytotoxic CD8+ T cells in our study population which could suggest the existance of compensatory mechanisms for Mtb-infected cells elimination in the face of severe CD4+ T cell lymphopenia. We also investigated the correlation between T lymphocyte activation profiles and the abundance of several inflammatory molecules in plasma. We applied unsupervised machine learning techniques to predict and diagnose TB-IRIS before and during ART. Our analyses suggest that CD4+ T cell activation markers are good TB-IRIS predictors, whereas the combination of CD4+ and CD8+ T cells markers are better at diagnosing TB-IRIS patients during IRIS events Overall, our findings contribute to a more refined understanding of immunological mechanisms in TB-IRIS pathogenesis that may assist in new diagnostic tools and more targeted patient management.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

et al. 2021

View full text Add to dashboard Cite

show abstract

“…While corticosteroids remain the only trial-supported medication for the prevention and management of TB-IRIS, biologic medicines that directly target the immunological pathology are gaining traction. TB-IRIS, particularly in its unmasking form, is still poorly understood, and further research is needed to verify biomarkers for diagnosis, as found by [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Diagnosis of Abdominal Tuberculosis in the Adult—Literature Review

Ionescu

Nicolescu

Madge³

et al. 2021

Diagnostics

View full text Add to dashboard Cite

Tuberculosis (TB) is a public health issue that affects mostly, but not exclusively, developing countries. Abdominal TB is difficult to detect at first, with the incidence ranging from 10% to 30% of individuals with lung TB. Symptoms are non-specific, examinations can be misleading, and biomarkers commonly linked with other diseases can also make appropriate diagnosis difficult. As a background for this literature review, the method used was to look into the main characteristics and features of abdominal tuberculosis that could help with differentiation on the PubMed, Science Direct, and Academic Oxford Journals databases. The results were grouped into three categories: A. general features (the five forms of abdominal tuberculosis: wet and dry peritonitis, lymphadenopathy, lesions at the level of the cavitary organs, lesions at the level of the solid organs), B. different intra-abdominal organs and patterns of involvement (oesophageal, gastro-duodenal, jejunal, ileal, colorectal, hepatosplenic, and pancreatic TB with calcified lymphadenopathy, also with description of extraperitoneal forms), and C. special challenges of the differential diagnosis in abdominal TB (such as diagnostic overlap, the disease in transplant candidates and transplant recipients, and zoonotic TB). The study concluded that, particularly in endemic countries, any disease manifesting with peritonitis, lymphadenopathy, or lesions at the level of the intestines or solid organs should have workups and protocols applied that can confirm/dismiss the suspicion of abdominal tuberculosis.

show abstract

“…Glucocorticoids are also one of the mainstays of TB-IRIS management; use of other agents like anakinra and anti-TNFα have been also reported in steroid-resistant cases [ 19 , 20 ]. Of note, the patient presented IRIS even if ART was started seven weeks after anti-TB drugs.…”

Section: Discussionmentioning

confidence: 99%

Concurrence of cat-scratch disease and paradoxical tuberculosis-IRIS lymphadenopathy: a case report

Eleftheriotis

Skopelitis

2022

BMC Infect Dis

View full text Add to dashboard Cite

Background Mycobacterial infections can cause significant morbidity when cellular immunity is compromised. Patients with AIDS can be affected directly from infection or through mycobacterial IRIS, especially if they are previously untreated for HIV. Herein a case of tuberculous lymphadenitis is reported, which primarily responded to antimicrobials but complicated by IRIS and cat-scratch disease at a later course. Case presentation A 23-year-old man, intravenous drug user with untreated HIV and HCV infection presented with fever and painful cervical lymphadenopathy. Mycobacterium tuberculosis was isolated from PCR and culture of ultrasound-guided lymph node aspirate and a four-drug anti-TB regimen was subsequently administered, leading to complete resolution of clinical and laboratory abnormalities. Given the patient’s CD4 count (67 cells per mm3), antiretroviral treatment started seven weeks after TB treatment initiation. Within the first month of ART fever recurred along with cervical lymph node inflammation. Paradoxical IRIS was considered as the most probable diagnosis but workup expanded, revealing acute Bartonella infection. A posteriori, the patient remembered being scratched by a stray cat two weeks before his new symptoms started. Doxycycline and corticosteroid monotherapy failed to resolve symptoms, whereas a combination of doxycycline for 3 months and methylprednisolone with long-term tapering led to negative follow-up Bartonella antibodies and complete clinical and biochemical response, without recurrence. Conclusions Co-infection with TB and Bartonella presenting with lymphadenitis is unusual. Cat-scratch disease can be a rare clinical presentation of Bartonella infection in patients with AIDS, but coexistence of bartonellosis and paradoxical IRIS has never been reported before. However, physicians treating people living with HIV should be aware of this potential concurrence. Early testing for Bartonella infection could be offered in patients with TB and HIV co-infection in case of acute deterioration or partial response to treatment, especially if they have a history of cat exposure, since clinical picture can be indistinguishable.

show abstract

Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease

Cited by 39 publications

References 176 publications

Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

Differential Diagnosis of Abdominal Tuberculosis in the Adult—Literature Review

Concurrence of cat-scratch disease and paradoxical tuberculosis-IRIS lymphadenopathy: a case report

Contact Info

Product

Resources

About