Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism.
We report the case of a 50-year-old ...woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis.
The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis.
Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.
El ensayo de liberación de interferón gamma (IGRA) se utiliza para detectar tuberculosis latente antes de los tratamientos biológicos en el contexto de sospecha de reumatismo inflamatorio.
Presentamos el caso de una mujer de 50 años con IGRA negativo antes de la introducción de adalimumab por presunta espondiloartritis axial.
El empeoramiento de los síntomas bajo tratamiento llevó a nuevas investigaciones y posteriormente se estableció el diagnóstico de tuberculosis (TB) diseminada con localizaciones pulmonar y óseas múltiples como espondilitis y sacroilitis. La historia de la paciente reveló una exposición pasada a la TB. Esta observación ilustra las limitaciones del IGRA en tal situación debido a su rendimiento variable para el diagnóstico de la TB activa.
El diagnóstico erróneo es frecuente en la TB ósea debido a signos inespecíficos. Llamamos la atención sobre la importancia de una evaluación de riesgo global antes de la introducción de un tratamiento biológico para la sospecha de reumatismo inflamatorio crónico, y recordamos los factores de riesgo para falsos negativos del IGRA. Puede ser necesario un curso de tratamiento prolongado después de la exposición al tratamiento anti-TNF-alfa.
•Both cellular and humoral immune responses to SARS-CoV-2 vaccination wane over time.•The rate of vaccine response decline is comparable between immunosuppressed patients and healthy populations.•S1P ...receptor modulators and mycophenolate are associated with lower cellular and humoral immune response.•Anti-CD20 therapy is associated with lower humoral immune response only.•35% of patients with poor humoral response after primary vaccination had a significantly increased humoral response after receiving the booster.
: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.
: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.
: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.
: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
•We used an IGRA to analyze a T-cell response in COVID-19 patients and healthy unexposed controls.•We show that 80% of the convalescent COVID-19 patients had reactive T cells to SARS-CoV-2 ...antigens.•Surprisingly, 44% of the unexposed controls also had a strong T-cell response to these antigens.•We suggest a pre-existing immunity because of T-cells, primed against SARS-CoV-2-like antigens before the start of the pandemic.
Studies of T-cell immune responses against SARS-CoV-2 are important in understanding the immune status of individuals or populations. Here, we use a simple, cheap, and rapid whole blood stimulation assay - an Interferon-Gamma Release Assay (IGRA) - to study T-cell immunity to SARS-CoV-2 in convalescent COVID-19 patients and in unexposed healthy contacts from Quito, Ecuador.
Interferon-gamma (INF-γ) production was measured in the heparinized blood of convalescent and unexposed subjects after stimulation for 24 h with the SARS-CoV-2 Spike S1 protein, the Receptor Binding Domain (RBD) protein or the Nucleocapsid (NP) protein, respectively. The presence of IgG-RBD protein antibodies in both study groups was determined with an “in-house” ELISA.
As measured with INF-γ production, 80% of the convalescent COVID-19 patients, all IgG-RBD seropositive, had a strong T-cell response. However, unexpectedly, 44% of unexposed healthy controls, all IgG-RBD seronegative, had a strong virus-specific T-cell response with the COVID-19 IGRA, probably because of prior exposure to common cold-causing coronaviruses or other viral or microbial antigens.
The high percentage of unexposed healthy subjects with a pre-existing immunity suggests that a part of the Ecuadorian population is likely to have SARS-CoV-2 reactive T-cells. Given that the IGRA technique is simple and can be easily scaled up for investigations where high numbers of patients are needed, this COVID-19 IGRA may serve to determine if the T-cell only response represents protective immunity to SARS-CoV-2 infection in a population-based study.
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Disease modifying therapies compromise immune response to SARS-Cov2 or its vaccine in patients with immune system diseases (ISD). Therefore, analysis of the humoral and cellular responses against ...Spike is of utmost importance to manage ISD patients. A single-center retrospective study was conducted to evaluate the impact of COVID-19 immunization in 87 ISD patients and 81 healthy controls. We performed a whole blood interferon gamma release assay using SARS-Cov2 Spike and Nucleocapsid recombinant proteins in order to evaluate T-cell memory response, and an IgG anti-Spike ELISA to evaluate humoral response. Cellular (26.4%) and humoral (44.8%) responses were negative against Spike in ISD patients following COVID-19 immunization. In univariate analysis, an anti-Spike T cell defective response was associated with the use of glucocorticoids (Odds ratio OR = 10.0; p < 10−4), serum albumin level ≤40 g/L (OR = 18.9; p < 10−4), age over 55 years old (OR = 3.9, p = 0.009) and ≤2 vaccine injections (OR = 4.9; p = 0.001). The impact of glucocorticoids persisted after adjustment for age and number of vaccine injections (OR = 8.38, p < 0.001). In contrast, the humoral response was impacted by the use of anti-CD20 mAb (OR = 24.8, p < 10−4), and an extended time since immunization (≥75 days; OR = 4.3, p = 0.002). Double defective cellular/humoral responses (6.9%) were typically encountered in glucocorticoids and/or anti-CD20 mAb treated ISD with a serum albumin level ≤40 g/L (OR = 17.5; p = 0.002). Glucocorticoid usage, B cell depleting therapies, and a low serum albumin level were the main factors associated with a non-response to COVID-19 immunization in ISD patients. These results need further confirmation in larger studies.
•Anti-Spike cellular and humoral responses are altered in immune system diseases.•Anti-Spike cellular response is affected by long-term glucocorticoid usage.•Anti-Spike humoral response is impaired by B-cell depleting and glucocorticoid therapies.•Serum albumin level, time from immunization, and >55 years old constitute additional risks for defective immune responses.
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Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive ...immune status, and disease severity in TBM patients.
We conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023.
The absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (
< 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (
< 0.05), and slightly higher than that in NSTB group (36.0%) (
> 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (-) group, and antibody (+) group were lower than that in simple TBM group, etiology (-) group, IGRA (+) group, and antibody (-) group, respectively. The CD3
T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (
< 0.05). The counts of CD3
T, CD4
T, and B cells in the etiology (+) group were significantly lower than those in the etiology (-) group (
< 0.05).
The absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.
BACKGROUND: South Texas has higher TB disease incidence than much of the United States. We evaluated a multi-site South Texas interferon-gamma release assay (IGRA)-based testing and latent TB ...infection (LTBI) treatment program targeting high-risk populations.METHODS:
Number of IGRA tests, test results, LTBI confirmation, and treatment outcomes were collected over 2.5 years. Sixteen semi-structured patient interviews and 10 site-based focus groups were conducted with providers, nurses, and administrators. Grounded theory identified themes associated with
successful outcomes.RESULTS: Of 9,050 IGRA tests, 687 (8%) were positive; 340 (49%) confirmed as LTBI; 191 initiated LTBI treatment; and 130 (68% of initiators) completed treatment. Patient barriers to treatment completion included lack of knowledge, misconceptions, and treatment
toxicities. Clinic staff concurred that toxicity was a barrier to treatment and requiring new processes with limited resources were implementation barriers.CONCLUSIONS: Over 9,000 patients were screened with a high prevalence of IGRA positivity, but confirming LTBI, initiating,
and completing treatment were challenging. Qualitative evaluation supports low literacy patient education on LTBI and toxicities and expanded support for process implementation and provider training. These findings highlight challenges at all levels of the LTBI care cascade and provide patient,
staff, and provider perspectives on implementation of these programs.
Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are ...commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals.
Participants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples.
A total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance.
The MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.
Guided biomarker-personalized immunotherapy is advancing rapidly as a means to rejuvenate immune function in injured patients who are the most immunosuppressed. A recent study introduced a fully ...automated interferon-γ release assay (IGRA) for monitoring the functionality of T lymphocytes in patients with septic shock. While a significant decrease in IFN-γ release capacity was observed, a significant correlation with CD8 lymphocyte absolute count was also reported, raising the question of whether ex-vivo IFN-γ production would be only a surrogate marker for lymphocyte count or if these two parameters conveyed distinct and complementary information. In a large cohort of more than 353 critically ill patients following various injuries (sepsis, trauma, major surgery), the primary objective of the present study was to simultaneously evaluate the association between ex vivo IFN-γ release and CD8 cell count with regard to adverse outcome. Our findings provide a clear-cut result, as they distinctly demonstrate that IGRA offers higher-quality information than CD8 count in terms of an independent association with the occurrence of an adverse outcome. These results strengthen the case for incorporating IGRA into the array of biomarkers of interest for defining endotypes in sepsis. This holds especially true given that fully automated tests are now readily available and could be used in routine clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection ...risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs).
We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring.
Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio OR, 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response.
HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.
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