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Objective: Sabirnetug (ACU193) is a humanized monoclonal antibody selective for soluble amyloid beta oligomers (AβOs), synaptotoxins that are early and persistent triggers of Alzheimer's disease (AD). Sabirnetug pharmacodynamics were examined in the INTERCEPT-AD phase 1 study in mild cognitive impairment and mild dementia due to AD (NCT04931459) using biofluid biomarkers associated with Aβ and tau pathology, synaptic dysfunction, neuroinflammation, and neurodegeneration., Methods: INTERCEPT-AD was a randomized, first-in-human study of sabirnetug versus placebo administered as a single (SAD; 2, 10, 25, 60 mg/kg) or multiple (MAD; three doses of 10 or 60 mg/kg every 4 weeks [Q4W] or 25 mg/kg Q2W) ascending doses. Biomarkers were measured pre-/post-dose in CSF and EDTA-plasma. Correlations of biomarker changes versus dose, exposure duration, and target engagement were determined., Results: In MAD cohorts, CSF pTau181 decreased significantly (60 mg/kg Q4W, p = 0.049). VAMP2 decreased significantly at all doses (p ≤ 0.041); neurogranin decreased significantly at 60 mg/kg Q4W (p = 0.037). Aβ 1-42 /Aβ 1-40 trended upward with sabirnetug dose. Aβ 1-42 /Aβ 1-40 and neurogranin changes correlated with sabirnetug-AβO target engagement (p ≤ 0.01). Decreases in tTau, VAMP2, and neurogranin correlated with exposure duration (p ≤ 0.007). Plasma pTau181, pTau217, GFAP, and NfL trended lower., Discussion: Following three sabirnetug doses, changes in CSF and plasma biomarkers were observed. The CSF biomarker response increased with increasing dose and exposure duration, consistent with previous reports that sabirnetug reaches the central compartment and engages its AβO target. The ongoing phase 2 ALTITUDE-AD study (NCT06335173) will test whether sabirnetug's pharmacodynamic effects can be substantiated with a larger sample size and longer treatment duration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erika N. Cline, Karen Sundell, Elizabeth Johnson, Maddelyn Hyland, Hao Zhang, Gopalan Sethuraman, Todd Feaster, Eric Siemers, and Jasna Jerecic are employees of, and minor stockholders in, Acumen Pharmaceuticals, Inc. Hugo Vanderstichele, June Kaplow, and Robert A. Dean are paid consultants of Acumen Pharmaceuticals, Inc Eugeen Vanmechelen and Erik Stoops are employees of ADx NeuroSciences, which provided services under contract to Acumen Pharmaceuticals, Inc. Charlotte E. Teunissen received grants of research funding from the European Commission, the European Partnership on Metrology, The Duch Research Council, The Alzheimer's Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Topsector Life Sciences & Health, Acumen Pharmaceuticals, ADX Neurosciences, AC Immune, Alamar, Aribio, Axon-Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapy, EIP Pharma, Eisai, Eli Lilly and Company, Fijirebio, Instant Nano Biosciences, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, and Vivoryon. She received consulting and or speaking fees from Aribio, Biogen, Beckman-Coulter, Cognition Therapy, Eli Lilly and Company, Merck, Novo Nordisk, Olink, Roche, and Veravas. Daniel Antwi-Berko and Marleen J.A. Koel-Simmelink declare no conflict of interests., (Copyright © 2025. Published by Elsevier Masson SAS.)

Background: Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed a comprehensive method comparison study, followed by evaluation of the diagnostic performance of eight recent plasma p-tau immunoassays targeting different tau phosphorylation sites, different tau fragments, and that are measured by two distinct platforms., Methods: We enrolled a cohort of 40 patients with AD at the stage of dementia (AD-dem) characterized by positive CSF A + T + profile, and a control group of 40 cognitively healthy participants (Control), to conduct a comprehensive method comparison for three plasma p-tau181 and five plasma p-tau217 assays run on the Simoa ® HD-X™ or Lumipulse ® G600II/G1200 platforms. Design of the compared assays differed in regard to: (1) tau phosphorylation site targeted by the capture antibody (T181 or T217), and (2) epitope of the pan-tau detector antibody (N-terminal or mid-region). For each of the assays we determined precision and analytical sensitivity parameters and used Passing-Bablok regression and Bland-Altman plots for pairwise comparison of p-tau181 or p-tau217 assays. Subsequently, we evaluated the diagnostic accuracy of all the assays for discrimination between AD-dem and Control groups., Results: We found a strong, positive correlation between all the measurements. Fixed and/or proportional bias was observed for each of compared p-tau181 assay pairs or p-tau217 assay pairs. While both plasma p-tau181 and p-tau217 levels were significantly increased in AD-dem vs. Control groups as measured by all assays, higher median concentration AD-dem/Control fold change and AUC values were observed for p-tau217 (assays range: fold change 3.72-6.74, AUC 0.916-0.956) compared with p-tau181 (assays range 1.81-2.94, AUC 0.829-0.909), independently of the platform used. No significant differences were observed between diagnostic performance of p-tau181 assays or p-tau217 assays targeting tau N-terminus or mid-region., Conclusions: Although all plasma p-tau measurements enabled discrimination between clinical groups, p-tau217 assays showed the highest robustness, independently of the pan-tau detector antibody targeting N-terminal or mid-region, and independently of the platform used. Considering the observed method disagreement in measured absolute concentrations, we stress the need for development of certified reference material, harmonizing measurements across different platforms., Competing Interests: Declarations. Ethics approval and consent to participate: All participants gave written informed consent to use medical data and biomaterial for research purposes. Ethical approval of the Amsterdam UMC VUmc medical ethical committee was in place, and the study was performed in accordance with the Helsinki Declaration of 1975. Consent for publication: Not applicable. Competing interests: JV, CL, MVL, and ES are employees of ADx NeuroSciences, part of the Fujirebio group. NB and MV are employees of Fujirebio Europe. AJ is an employee of ALZpath, Inc and has stock options. CET is employed by Amsterdam UMC and she has grants or contracts for Research of the European Commission (Marie Curie International Training Network, grant agreement No. 860197 (MIRIADE), Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434) EPND ( IMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance), Alzheimer Drug Discovery Foundation, Alzheimer Association, Health Holland, the Dutch Research Council (ZonMW), including TAP-dementia, a ZonMw funded project (#10510032120003) in the context of the Dutch National Dementia Strategy, Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands. CET is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). CET is also a contract researcher for ADx Neurosciences, AC-Immune, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Siemens, Toyama, Vivoryon, and the European Commission. CET has received payment or honoraria from Roche, Novo Nordisk, and Grifols, where all payments were made to her institution. CET also serves on editorial boards of Medidact Neurologie/Springer; and in Neurology: Neuroimmunology & Neuroinflammation. She is editor of Alzheimer Research and Therapy. Research programs of Wiesje van der Flier (WF) have been funded by ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. WF holds the Pasman chair. WF is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). WF is recipient of TAP-dementia (www.tap-dementia.nl), receiving funding from ZonMw (#10510032120003). TAP-dementia receives co-financing from Avid Radiopharmaceuticals, Roche, and Amprion. All funding is paid to her institution.WF has been an invited speaker at Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), NovoNordisk, Springer Healthcare, European Brain Council. All funding is paid to her institution.WF is consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. All funding is paid to her institution. WF participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. WF is member of the steering committee of EVOKE/EVOKE+ (NovoNordisk). All funding is paid to her institution.WF is member of the steering committee of PAVE, and Think Brain Health. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is associate editor at Brain. Inge M.W.Verberk received a speaker honorarium from Quanterix, which was paid directly to her institution. All the other authors have nothing to disclose., (© 2024. The Author(s).)

Background: Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development., Methods: We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01-01-2017 and 01-01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type., Results: We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers., Conclusions: As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets., (© 2024. The Author(s).)

Background: In onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission, a high prevalence of epilepsy has been reported. This study aimed to determine the prevalence and clinical characteristics of epilepsy in the Bono Region of Ghana following 27 years of implementation of ivermectin mass drug administration (MDA)., Methods: Between October 2020 and August 2021, cross-sectional surveys were conducted in nine communities in the Tain District and Wenchi Municipality of the Bono Region of Ghana. In the first stage, a random door-to-door approach was used to screen the population for epilepsy using a pre-tested questionnaire. Persons suspected of having epilepsy were invited for a second-stage neurological examination for case verification. Community O. volvulus microfilarial infection status and Ov16 seropositivity were also determined. Ninety-five confidence intervals (95% CI) for prevalence values were calculated using the Wilson Score Interval., Results: Of the 971 participants, 500 (51.5%) were females, and the median age (interquartile range) was 26 (15‒43) years. Fourteen participants (1.4%, 95% CI: 1.0‒2.0) were diagnosed as having epilepsy with generalized seizures being the most frequent seizure type (85.7%, 12/14). The overall microfilarial prevalence of O. volvulus was 10.3% (November 2020) and 9.9% (August 2021); the Ov16 seroprevalence was 22.2% (June 2021). Only 63.2% took ivermectin in the last round of MDA distribution in March 2021., Conclusions: The 1.4% prevalence of epilepsy in the Bono region is similar to the median epilepsy prevalence in sub-Saharan Africa. However, the persistent microfilarial prevalence and low ivermectin study coverage call for the Ghana Onchocerciasis Elimination Programme to step up its efforts to ensure that the gains achieved are consolidated and improved to achieve the elimination of onchocerciasis by 2030., (© 2023. National Institute of Parasitic Diseases.)

Background: T cell receptors play important roles in the development and progression of rheumatoid arthritis (RA). Their involvement has been reported in inflammatory autoimmune diseases. However, their role in predicting RA is still under exploration. This study evaluated the expression of CD183 (CXCR3) receptors on T-cells and other relevant biomarkers for detecting RA and determine their relationship with disease activity., Methods: This unmatched case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from the orthopedic units of Komfo Anokye Teaching Hospital (KATH), Kumasi and Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. Sociodemographic data was obtained, and blood samples were also collected and processed for flow cytometric analysis. Statistical analyses were done using SPSS version 26.0 and R programming language. p < .05 was considered statistically significant., Results: This study found a significant difference in age group (p < .0001), marital status (p = .0210), occupation (p = .0140), educational level (p = .0210) and religion (p = .0100) between RA patients and healthy controls. Moreover, hemoglobin level (p = .0010), waist circumference (p < .0001) and hip circumference (p = .0040) were significantly different between RA patients and controls. RA patients had significantly lower levels of CD4 + CD183 + compared with the control group (p < .001), and was positively correlated with DAS score (r = .0397, p = .789). In Receiver Operator Characteristics analysis, CD4 + CD183 + could significantly detect RA with a high area under the curve (AUC = 0.687, p = .018). At a cut-off of 0.082, CD4 + CD183 + was the best receptor biomarker for detecting RA with a sensitivity of 90.0%, specificity of 25.9%, a positive predictive value of 69.2%, and a negative predictive value of 58.3%., Conclusion: CD4 + CD183 + best predict RA and is positively correlated with disease activity. CD4 + CD183 + could serve as diagnostics and disease-monitoring biomarker for RA; however, it demonstrates low specificity. Future studies should be directed on CD4 + CD183 + and other biomarkers to augment their diagnostics performances and routine management in RA., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Doxycycline is used for treatment of Mansonella perstans infection. Immune modulatory effects of both M. perstans and doxycycline have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans-infected individuals before and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity., Methods: Immune characterization of doxycycline-treated M. perstans-infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, 6 months, and "long term" (18-24 months) after treatment start. Treatment efficacy, based on peripheral blood microfilaria (mf) burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined., Results: Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen-induced T-cell activation and polarization towards T-helper type (TH) 1 phenotype at baseline declined after doxycycline treatment, whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant M. tuberculosis infection was seen. Notably, only TH17 and TH1* changes after 6 months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction, whereas long-term changes were not associated with treatment efficacy., Conclusions: We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant M. tuberculosis infection., Competing Interests: Potential conflicts of interests. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Immune-based diagnosis of Buruli ulcer disease (BUD) in children is difficult due to cross-reactivity between mycobacteria. We found that T-cell IFNγ/TNFα responses against Mycobacterium (M.) ulcerans and M. tuberculosis (PPDMulc, PPDMtub) were different between children with BUD (n = 27) and TB (n = 20) but only ratios (PPDMtub/PPDMulc) discriminated the study groups efficiently., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The Research on Obesity and Diabetes among African Migrants (RODAM) prospective (RODAM-Pros) cohort study was established to identify key changes in environmental exposures and epigenetic modifications driving the high burden of cardiovascular disease (CVD) risk among sub-Saharan African migrants., Participants: All the participants in the RODAM cross-sectional study that completed the baseline assessment (n=5114) were eligible for the follow-up of which 2165 participants (n=638 from rural-Ghana, n=608 from urban-Ghana, and n=919 Ghanaian migrants in Amsterdam, the Netherlands) were included in the RODAM-Pros cohort study. Additionally, we included a subsample of European-Dutch (n=2098) to enable a comparison to be made between Ghanaian migrants living in the Netherlands and the European-Dutch host population., Findings to Date: Follow-up data have been collected on demographics, socioeconomic status, medical history, psychosocial environment, lifestyle factors, nutrition, anthropometrics, blood pressure, fasting blood, urine and stool samples. Biochemical analyses included glucose metabolism, lipid profile, electrolytes and renal function, liver metabolism and inflammation. In a subsample, we assessed DNA methylation patterns using Infinium 850K DNA Methylation BeadChip. Baseline results indicated that migrants have higher prevalence of CVD risk factors than non-migrants. Epigenome-wide association studies suggest important differences in DNA methylation between migrants and non-migrants. The follow-up study will shed further light on key-specific environmental exposures and epigenetic modifications contributing to the high burden of CVD risk among sub-Saharan African migrants., Future Plans: Follow-up is planned at 5-year intervals, baseline completed in 2015 and first follow-up completed in 2021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple media platforms and various resources are available for information on the novel coronavirus disease (COVID-19). Identifying people's preferences is key to building public confidence and planning for successful national or regional health intervention strategies., Methods: Using exploratory mixed-methods including a short survey, interviews and participant observation, this cross-sectional study of 160 respondents from the Ghanaian-Dutch, Afro and Hindustani Surinamese-Dutch communities in Amsterdam, the Netherlands was conducted. Data collected between February to April 2021, included demographics characteristics, knowledge, opinions, preferred source of information, behavioral factors, and information gaps on COVID-19 prevention measures, responses and decision-making of respondents. Descriptive statistics and follow-up in-depth interviews were conducted to determine the relationship between respondents' demographics, information sources, and attitudes/behaviors toward COVID-19., Results: The findings of this study indicated that although many of the respondents from these communities had good knowledge on COVID-19, its modes of transmission and prevention measures, their willingness to take up initiatives and prioritize self responsibility toward their health are tied to their communal life. The respondents in this study demonstrated high value for social lives and relied on their connections with friends and families in shaping, obtaining, processing and utilizing COVID-19 information to build a sense of responsibility toward the uptake of COVID-19 prevention measures despite recent decline in number of cases., Conclusion: This sense of responsibility means their active participation and ownership of interventions to address the specific personal concerns and that of their community. However, different factors play influential roles toward the behavior choices of our respondents regarding the COVID-19 prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bakuri and Antwi-Berko.)

The outbreak of the deadly novel coronavirus disease (COVID-19) has disrupted life worldwide in an unprecedented manner. Over the period, scientific breakthroughs have resulted in the rollout of many vaccination programmes to protect against the disease, reduce the fear and ease public health restrictions for lives to return to some normalcy. The aim of this study was to identify the factors responsible for COVID-19 vaccine acceptance or vaccine hesitancy and to develop a framework to improve vaccine uptake in the Ghanaian-Dutch, Afro and Hindustani Surinamese-Dutch communities in Amsterdam. Using a mixed method approach, this community-based cross-sectional survey recruited 160 respondents consisting of 57 Ghanaian-Dutch, 54 Afro Surinamese-Dutch and 49 Hindustani-Dutch residents in Amsterdam. Our findings showed that the choice of a vaccine as well as the likelihood of self-reported willingness to receive a vaccine is highly dependent on vaccine efficacy and safety. Available evidence of high vaccine effectiveness and safety could encourage about 41.3% of the respondents to accept the vaccine. Additionally, 69.6% of the respondents indicated their willingness to accept the vaccine when vaccine passports are made mandatory by the government. Other major factors that could drive the likelihood of accepting the COVID-19 vaccine include travel requirement for vaccination (28.3%), the safety/probability of only minor side effects (26.1%) and recommendation by family and friends (15.2%). The study therefore provides systematic evidence of factors associated with individual preferences toward COVID-19 vaccination. It demonstrates that the needs of each community are unique and specific interventional efforts are urgently needed to address concerns likely to be associated with vaccine hesitancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antwi-Berko, Bakuri, Otabil and Kwarteng.)

The burden of infectious disease in developing countries is substantially higher than in developed nations. Reasons include poor health care infrastructure and deficiencies in public understanding of infectious disease mechanisms and disease prevention. While immunology education and research have an enviable role in understanding host-pathogen interactions, training programs in immunology remain fully integrated into the curricula of higher institutions, and by extension, to high schools of developing nations. Therefore, we discussed the need to make major investments in immunology research and research training into all natural sciences teaching curricula, particularly in developing countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kwarteng, Sylverken, Antwi-Berko, Ahuno and Asiedu.)

Background: T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. However, their role in RA within hitherto rare Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4+ T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity., Methods: This case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for flow cytometric analysis., Results: IFN- γ , TNF- α , IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4, and IL-17/IL-10 expressions were significantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs. 0.82 (0.34-1.10) vs. 1.56 (1.39-1.68), p < 0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), p < 0.0001), and IL-17A/IL-10 (0.00 (0.00-0.39) vs. 0.15 (0.09-0.26) vs. 0.88 (0.41-1.47), p < 0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 ( β = 0.681, r 2 = 0.527, p < 0.0001), IL-17A ( β = 0.770, r 2 = 0.593, p < 0.0001), and IL-17A/IL-10 ( β = 0.677, r 2 = 0.452, p < 0.0001) expressions were significantly directly associated with DAS28 scores. IL-6 (cutoff = 1.32, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and AUC = 1.000) and IL-17A (cutoff = 0.58, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and AUC = 1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores., Conclusion: Th1- and Th17-related cytokines predominate in the pathophysiology of RA, with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Samuel Asamoah Sakyi et al.)

Background: Buruli ulcer disease (BUD), caused by Mycobacterium (M.) ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. BUD causes necrotic skin lesions and is a significant problem for health care in the affected countries. As for other mycobacterial infections, T cell mediated immune responses are important for protection and recovery during treatment, but detailed studies investigating these immune responses in BUD patients are scarce. In this study, we aimed to characterise M. ulcerans-specific CD4+ T cell responses in BUD patients and to analyse specific cytokine-producing T cells in the context of disease severity and progression., Methodology/principal Findings: For this case-control study, whole blood samples of BUD patients (N = 36, 1.5-17 years of age) and healthy contacts (N = 22, 3-15 years of age) were stimulated with antigen prepared from M. ulcerans and CD4+ T cells were analysed for the expression of TNFα, IFNγ and CD40L by flow cytometry. The proportions and profile of cytokine producing CD4+ T cells was compared between the two study groups and correlated with disease progression and severity. Proportions of cytokine double-positive IFNγ+TNFα+, TNFα+CD40L+, IFNγ+CD40L+ (p = 0.014, p = 0.010, p = 0.002, respectively) and triple positive IFNγ+TNFα+CD40L+ (p = 0.010) producing CD4+ T cell subsets were increased in BUD patients. In addition, TNFα+CD40L-IFNγ- CD4+ T cells differed between patients and controls (p = 0.034). TNFα+CD40L-IFNγ- CD4+ T cells were correlated with lesion size (p = 0.010) and proportion were higher in 'slow' healers compared to 'fast healers' (p = 0.030)., Conclusions: We were able to identify M. ulcerans-specific CD4+ T cell subsets with specific cytokine profiles. In particular a CD4+ T cell subset, producing TNFα but not IFNγ and CD40L, showed association with lesion size and healing progress. Further studies are required to investigate, if the identified CD4+ T cell subset has the potential to be used as biomarker for diagnosis, severity and/or progression of disease.