scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Immune Reconstitution Inflammatory Syndrome with Recurrent Paradoxical Cerebellar HIV-Associated Progressive Multifocal Leukoencephalopathy

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 813
Author(s):  
Paola Frattaroli ◽  
Teresa A. Chueng ◽  
Obinna Abaribe ◽  
Folusakin Ayoade
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
People Living With Hiv ◽  
Rare Presentation ◽  
Diagnosis And Management ◽  
Art Initiation ◽  
Cerebellar Lesions ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML), presenting as immune reconstitution inflammatory syndrome (IRIS), is a known complication of antiretroviral therapy (ART) in people living with HIV (PLWH). Typically preceded by ART initiation, IRIS may appear simultaneously/unmasked (PML-s-IRIS) or as a delayed/worsening/paradoxical (PML-d-IRIS) presentation of known PML disease. Primary cerebellar tropism continues to be a rare presentation, and paradoxical cerebellar involvement of PML-IRIS syndrome can be a challenge for both diagnosis and management. Steroids have been suggested as a possible therapy in severe cases but the duration of steroid therapy remain elusive. Our case is that of a 34-year-old man with newly diagnosed HIV simultaneously found to have cerebellar PML. His PML lesions however worsened after initiation of ART (PML-d-IRIS) with evidence of increased intracranial pressure. Despite initial favorable response to a short duration of steroids, he had multiple recurrence of his PML lesions after steroids were discontinued. The presence of predominant cerebellar lesions and the question of how long steroids should be provided to prevent or minimize PML recurrence is the highlight of our case. This report emphasizes the need for more controlled studies to assist clinicians in the optimal diagnosis and management of PML-IRIS in PLWH.

scholarly journals Treatment with Tumor Necrosis Factor-α Inhibitors, History of Allergy, and Hypercalcemia Are Risk Factors of Immune Reconstitution Inflammatory Syndrome in HIV-Negative Pulmonary Tuberculosis Patients

2019 ◽  
Vol 9 (1) ◽  
pp. 96
Author(s):  
Yoshimasa Hachisu ◽  
Yasuhiko Koga ◽  
Shu Kasama ◽  
Kyoichi Kaira ◽  
Masakiyo Yatomi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Immune Reconstitution ◽  
Tumor Necrosis ◽  
Hiv Patients ◽  
Tnf Α ◽  
History Of ◽  
Inflammatory Syndrome ◽  
Necrosis Factor ◽  
Inhibitor Treatment

Immune reconstitution inflammatory syndrome (IRIS) is an immune reaction that occurs along with the recovery of the patient’s immunity. Tuberculosis-related IRIS (TB-IRIS) upon tumor necrosis factor (TNF)-α inhibitor treatment has been reported in non-human immunodeficiency virus (HIV) patients. However, the importance of biological treatment, as a risk factor of IRIS, has not yet been established. In this study, we examined TB-IRIS in non-HIV patients to explore the role of TNF-α inhibitor treatment. Out of 188 patients with pulmonary TB, seven patients had IRIS. We examined univariate logistic and multivariate analysis to elucidate risk factors of TB-IRIS. Univariate analysis indicated that usage of immunosuppressive drugs, TNF-α inhibitors, and history of food or drug allergy were significantly related with TB-IRIS. On initial treatment, the values of serological markers such as serum albumin and serum calcium were significantly related with TB-IRIS. There was a higher mortality rate in patients with TB-IRIS. Furthermore, multivariate analysis revealed that usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia were related to TB-IRIS. Usage of TNF-α inhibitors, history of allergy, and serum hypercalcemia may be independent predictors of TB-IRIS in non-HIV patients. Since higher mortality has been reported for TB-IRIS, we should pay attention to TB patients with these risk factors.

scholarly journals Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Aurelie Gouel-Cheron ◽  
Martha Nason ◽  
Adam Rupert ◽  
Virginia Sheikh ◽  
Greg Robby ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Antiretroviral Therapy ◽  
Chronic Inflammation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Art Initiation ◽  
History Of ◽  
Cardiovascular Biomarker ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event. ClinicalTrials.gov Identifier . NCT00286767.

scholarly journals Clinical and immunologic predictors of Mycobacterium avium complex immune reconstitution inflammatory syndrome in a contemporary cohort of patients with HIV

2020 ◽  
Author(s):  
Kimberly F Breglio ◽  
Caian L Vinhaes ◽  
María B Arriaga ◽  
Martha Nason ◽  
Gregg Roby ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
T Cell Activation ◽  
Mycobacterium Avium ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Mycobacterium Avium Complex ◽  
Subsequent Development ◽  
Art Initiation ◽  
Increased Risk ◽  
Inflammatory Syndrome

Abstract Background Patients with HIV (PWH) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS. Methods PWH with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naïve patients with CD4 <100 cells/µL. Results Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower BMI, lower hemoglobin levels, a higher alkaline phosphatase and increased CD38 frequency and MFI on CD8 + T-cells, at the time of ART initiation compared to non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of alkaline phosphatase and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of alkaline phosphatase at baseline were associated with increased risk of MAC-IRIS development. Conclusions High alkaline phosphatase levels and increased CD8 + T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS.

scholarly journals Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3818-3827 ◽  
Author(s):  
Lis R. V. Antonelli ◽  
Yolanda Mahnke ◽  
Jessica N. Hodge ◽  
Brian O. Porter ◽  
Daniel L. Barber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Interferon Γ ◽  
Effector Memory ◽  
Hiv Patients ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1+, HLA-DR+, and Ki67+ CD4+ T cells than patients without IRIS. Moreover, PD-1+ CD4+ T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767.

scholarly journals 1401. Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S785-S785
Author(s):  
Ahad Azeem ◽  
Faran Ahmad ◽  
Manasa Velagapudi
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Modulation ◽  
Immune Reconstitution ◽  
Clinical Symptoms ◽  
Latent Tuberculosis ◽  
High Dose ◽  
Mri Brain ◽  
Tnf Α ◽  
Inflammatory Syndrome ◽  
The Brain

Abstract Background Tumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy. Methods We report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor). Results A 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement. MRI Brain MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region. Conclusion Exacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents. Disclosures All Authors: No reported disclosures

Sign in / Sign up

Export Citation Format

Share Document