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Vaccines May 2024Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about...
BACKGROUND
Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about suboptimal immunogenicity, especially in humoral immunity (HMI), and limited exploration of cell-mediated immune (CMI) responses. The primary objective of this study was to assess the immunogenicity of ChAdOx1 nCoV-19 vaccination in SOT recipients. The secondary endpoint was to evaluate factors that affect immunogenicity and adverse events (AEs) following immunization in SOT recipients.
METHODS
All adult SOT recipients who received the two-dose ChAdOx1 nCoV-19 vaccine at a 12-week interval underwent measurements of HMI by evaluating anti-receptor-binding domain (RBD) IgG levels and CMI by investigating SARS-CoV-2-specific T cell and B cell responses before and after complete vaccination, around 2-4 weeks post-vaccination, and compared to controls. AEs were monitored in all participants.
RESULTS
The study included 63 SOT recipients: 44 kidney recipients, 16 liver recipients, and 3 heart transplant recipients, along with 11 immunocompetent controls. Among SOT recipients, 36% were female, and the median (IQR) age was 52 (42-61). The median (IQR) time since transplant was 55 (28-123) months. After the second dose, the median (IQR) anti-RBD antibody levels were significantly lower in SOT recipients compared to those in the control group (8.3 [0.4-46.0] vs. 272.2 [178.1-551.6] BAU/mL, < 0.01). This resulted in a seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) of 51% among SOT recipients and 100% among controls ( = 0.008). Receiving the vaccine beyond one year post-transplant significantly affected seroconversion (OR 9.04, 95% CI 1.04-78.56, = 0.046), and low-dose mycophenolic acid marginally affected seroconversion (OR 2.67, 95% CI 0.89-7.96, = 0.079). RBD-specific B cell responses were also significantly lower compared to those in the control group (0 [0-4] vs. 10 [6-22] SFUs/10 PBMCs, = 0.001). Similarly, S1- and SNMO-specific T cell responses were significantly lower compared to those in the control group (48 [16-128] vs. 216 [132-356] SFUs/10 PBMCs, = 0.004 and 20 [4-48] vs. 92 [72-320] SFUs/10 PBMCs, = 0.004). AEs were generally mild and spontaneously resolved.
CONCLUSIONS
SOT recipients who received the full two-dose ChAdOx1 nCoV-19 vaccine demonstrated significantly diminished HMI and CMI responses compared to immunocompetent individuals. Consideration should be given to administering additional vaccine doses or optimizing immunosuppressant regimens during vaccination (Thai Clinical Trial Registry: TCTR20210523002).
PubMed: 38793792
DOI: 10.3390/vaccines12050541 -
Biomedicines Apr 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia....
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.
PubMed: 38790929
DOI: 10.3390/biomedicines12050967 -
Journal of Autoimmunity May 2024Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc...
OBJECTIVES
Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc.
METHODS
This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed.
RESULTS
A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years.
CONCLUSION
SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.
PubMed: 38788540
DOI: 10.1016/j.jaut.2024.103246 -
Marine Drugs Apr 2024Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in...
Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.
Topics: Animals; Antiviral Agents; Influenza A virus; Mycophenolic Acid; Mice; Virus Replication; Humans; Orthomyxoviridae Infections; Mice, Inbred BALB C; Dogs; Female; Madin Darby Canine Kidney Cells; A549 Cells; Aquatic Organisms; Influenza, Human
PubMed: 38786581
DOI: 10.3390/md22050190 -
JPMA. the Journal of the Pakistan... May 2024To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. (Observational Study)
Observational Study Comparative Study
OBJECTIVES
To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis.
METHODS
The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26.
RESULTS
Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05).
CONCLUSIONS
Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.
Topics: Humans; Lupus Nephritis; Mycophenolic Acid; Cyclophosphamide; Female; Adult; Pakistan; Male; Immunosuppressive Agents; Tertiary Care Centers; Young Adult; Treatment Outcome; Cohort Studies; Tacrolimus; Induction Chemotherapy; Remission Induction
PubMed: 38783432
DOI: 10.47391/JPMA.8694 -
Modern Rheumatology Case Reports May 2024Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or...
Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or alongside other systemic symptoms. Here, we describe the case of a 45-year-old male with a history of recurrent sinusitis refractory to antibiotics, who presented to the emergency department with sinus congestion and dysphagia. Clinical examination revealed left lower motor neuron facial palsy and enlarged submandibular salivary glands. Despite obtaining negative results from various antibody panels, the patient exhibited elevated Angiotensin Converting Enzyme levels of 83 nmol/kg/min. Additionally, computed tomography chest scans revealed bilateral hilar and mediastinal lymph node enlargement, findings consistent with sarcoidosis. Otorhinolaryngology evaluation for dysphagia confirmed left vocal cord palsy. Following a negative infectious disease workup, submandibular salivary gland biopsy confirmed sarcoidosis. Treatment with mycophenolate mofetil and oral steroids led to gradual improvement in salivary gland swelling, dysphagia, and facial palsy. However, worsening left shoulder pain prompted further investigation, revealing winging of the left scapula on repeat examination. Magnetic resonance imaging (MRI) of the cervical spine revealed a six mm hyperintensity in the left dorsal cord at the C5 level, suggesting possible neurosarcoidosis vs. demyelinating disease. Subsequently, the patient was prescribed anti-tumor necrosis factor alpha inhibitor infliximab. Subsequent MRI of the cervical spine, conducted six months after initiating Infliximab therapy, indicated resolution of the lesions. This positive outcome was supported by the patient's report of symptom improvement, notably reduced shoulder pain and improvement in left scapular winging. This case underscores the unusual co-occurrence of Bell's palsy and vocal cord palsy in the same patient, along with the potential contribution of neurosarcoidosis to the winged scapula. Additionally, it sheds light on the positive response of neurosarcoidosis to Infliximab therapy.
PubMed: 38780235
DOI: 10.1093/mrcr/rxae030 -
Journal of Veterinary Internal Medicine May 2024Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions....
Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell-containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.
PubMed: 38779941
DOI: 10.1111/jvim.17079 -
Cureus Apr 2024Hypersensitivity pneumonitis (HP) is a pulmonary disease characterized by inflammation and fibrosis of the lung parenchyma following chronic exposure to immunogenic...
Hypersensitivity pneumonitis (HP) is a pulmonary disease characterized by inflammation and fibrosis of the lung parenchyma following chronic exposure to immunogenic antigens. The pathophysiology of HP involves type 3 and type 4 hypersensitivity reactions leading to acute and chronic manifestations, respectively. Clinically, it manifests as exertional dyspnea and wheezing. Pulmonary function tests display a pattern of restrictive lung disease, and high-resolution CT scans display a pattern of ground glass opacities, centrilobular nodules, and mosaic attenuation. Antigen avoidance remains the only method for primary prevention. Alternative therapy may be needed due to either the inability to avoid antigens or the lack of antigen identification. Prednisone 0.5 mg/kg per day is the first-line treatment for acute non-fibrotic forms of HP. In chronic or fibrotic HP, the immunomodulator mycophenolate mofetil (MMF) was shown to be an effective treatment in improving the diffusing capacity of the lungs for carbon monoxide and forced vital capacity, but not overall survival. The following study aims to bring to attention the need for additional prospective multicenter clinical trials to clarify the role of MMF as an immunomodulator in fibrosing HP.
PubMed: 38779275
DOI: 10.7759/cureus.58723 -
Journal of Neurology, Neurosurgery, and... May 2024The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established....
BACKGROUND
The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD.
METHODS
This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes.
RESULTS
The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab.
CONCLUSION
In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.
PubMed: 38777578
DOI: 10.1136/jnnp-2024-333644 -
The Analyst Jun 2024Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is...
Sea urchin nanostructured nickel cobaltite modified carbon cloth integrated wearable patches for the on-site detection of the immunosuppressant drug mycophenolate mofetil.
Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCoO) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCoO. The enhanced activity of NiCoO was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCoO was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCoO was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 μM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.
Topics: Animals; Nickel; Mycophenolic Acid; Immunosuppressive Agents; Carbon; Wearable Electronic Devices; Limit of Detection; Sea Urchins; Nanostructures; Electrochemical Techniques; Propylamines; Humans; Cobalt; Electrodes; Silanes
PubMed: 38775016
DOI: 10.1039/d4an00592a