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Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 110
Author(s):  
An-Che Cheng ◽  
Te-Yu Lin ◽  
Ning-Chi Wang

Antiretroviral therapy (ART) can restore protective immune responses against opportunistic infections (OIs) and reduce mortality in patients with human immunodeficiency virus (HIV) infections. Some patients treated with ART may develop immune reconstitution inflammatory syndrome (IRIS). Mycobacterium avium complex (MAC)-related IRIS most commonly presents as lymphadenitis, soft-tissue abscesses, and deteriorating lung infiltrates. However, neurological presentations of IRIS induced by MAC have been rarely described. We report the case of a 31-year-old man with an HIV infection. He developed productive cough and chronic inflammatory demyelinating polyneuropathy (CIDP) three months after the initiation of ART. He experienced an excellent virological and immunological response. Sputum culture grew MAC. The patient was diagnosed with MAC-related IRIS presenting as CIDP, based on his history and laboratory, radiologic, and electrophysiological findings. Results: Neurological symptoms improved after plasmapheresis and intravenous immunoglobulin (IVIG) treatment. To our knowledge, this is the first reported case of CIDP due to MAC-related IRIS. Clinicians should consider MAC-related IRIS in the differential diagnosis of CIDP in patients with HIV infections following the initiation of ART.


2022 ◽  
Author(s):  
Yang Zhou ◽  
Liu Pan ◽  
You-jun Yang ◽  
Shi-yu Li ◽  
Wei Yin ◽  
...  

Abstract Objective: The DAMPs such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. The aim of this study was to analyze the role of HMGB1,S100A12 and IL-17A in the detection of inflammation in KD patients with IVIG-resistant, and to investigate the value of different adjunctive therapy.Method: This study enrolled 126 patients diagnosed with KD, as well as age-matched 16 febrile control subjects. The demographic or clinical data, laboratory parameter and blood sample were collected. Various laboratory parameters as predictive factors for IVIG-resistant were calculated. And the serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in all patients. For patients with acute KD in IVIG-resistant, we studied the levels of laboratory variables when using of IVIG retreatment, methylprednisolone, infliximab for children patients. Result: The variance of laboratory parameters between the febrile control group and KD group were analyzed. Regarding laboratory parameters, KD individuals were found to have lower levels of L%, PA, CD4+, CD8+ and higher levels of WBC, N%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of blood S100A12, HMGB1, serum IL-17A levels And N%, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with acute KD in IVIG-resistant, after initial IVIG-treatment, the adjunctive therapy of IVIG, methyl prednisolone or infliximab were used, the inflammatory symptoms and laboratory inflammatory markers were improved when treated with those drugs. Conclusion: IVIG-resistant was associated with higher levels of HMGB1, S100A12, IL-17A, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT before IVIG, especially when combined, were useful predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relief clinical symptoms than IVIG retreatment.


2021 ◽  
pp. 1-13
Author(s):  
Hironobu Nakayama ◽  
Hiroyasu Inada ◽  
Tatsuya Inukai ◽  
Kenta Kondo ◽  
Kazuyuki Hirai ◽  
...  

<b><i>Introduction and Objective:</i></b> Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis. <b><i>Methods:</i></b> An animal model of KD-like vasculitis was created by injecting mice with <i>Candida albicans</i> water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues. <b><i>Results:</i></b> rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels. <b><i>Conclusion:</i></b> These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.


2021 ◽  
Author(s):  
Laura McCulloch ◽  
Alison J. Harris ◽  
Alexandra Malbon ◽  
Michael J. D. Daniels ◽  
Mehwish Younas ◽  
...  

Post-stroke infection is a common complication of stroke that is associated with increased mortality and morbidity. We previously found that experimental stroke induces an ablation of multiple sub-populations of B cells and reduced levels of IgM antibody that coincide with the development of spontaneous bacterial pneumonia. Reduced circulating IgM concentrations were also observed in acute stroke patients. The loss of IgM antibody after stroke could be an important determinant of infection susceptibility and highlights this pathway as an important target for intervention. We treated mice with a low (replacement), dose of IgM-enriched intravenous immunoglobulin (IgM-IVIg) prior to and 24 h after experimental stroke induced by middle cerebral artery occlusion (MCAO) or sham surgery, then recovered mice for 2 d or 5 d. The effect of treatment on lung bacterial burden, lung pathology, brain infarct volume, antibody levels and both lung and systemic cellular and cytokine immune profiles was determined. Treatment with IgM-IVIg enhanced bacterial clearance from the lung after MCAO and improved pathology but did not impact infarct volume. IgM-IVIg treatment induced immunomodulatory effects systemically including rescue of splenic plasma B cell numbers and endogenous mouse IgM and IgA circulating immunoglobulin concentrations that were reduced by MCAO, and treatment also reduced concentrations of pro-inflammatory cytokines in the lung. The effects of MCAO and IgM-IVIg treatment on the immune system were tissue specific as no impact on B cells or mouse immunoglobulins were found within the lung. However, the presence of human immunoglobulins from the IgM-IVIg treatment led to increased total lung immunoglobulin concentration. IgM-IVIg treatment did not increase the number of lung mononuclear phagocytes or directly modulate macrophage phagocytic capacity but enhanced their capability to phagocytose Staphylococcus aureus bioparticles in vitro by increasing opsonisation. Low dose IgM-IVIg contributes to increased clearance of spontaneous lung bacteria after MCAO likely via increasing availability of antibody in the lung to enhance phagocytic activity. Immunomodulatory effects of IgM-IVIg treatment, including reduced pro-inflammatory cytokine production, may also contribute to reduced levels of damage in the lung after MCAO. IgM-IVIg shows promise as an antibacterial and immunomodulatory agent to use in the treatment of post-stroke infection.


2021 ◽  
Vol 9 ◽  
Author(s):  
Benno Kohlmaier ◽  
Heidemarie Holzmann ◽  
Karin Stiasny ◽  
Manuel Leitner ◽  
Christoph Zurl ◽  
...  

Background: Administration of measles virus (MV)-specific IgG as post-exposure prophylaxis (PEP) is known to effectively prevent measles. Since the introduction of active immunization against measles, the levels of MV-specific IgG antibodies in the population have dropped. Therefore, the concentration of MV-specific antibodies in immunoglobulin products derived from human plasma donors has declined as the proportion of vaccinated donors has increased. Literature on the effectiveness of PEP with current available immunoglobulins is limited. Here we examine the effectiveness of 400 mg/kg intravenous immunoglobulin (IVIG) (IgVena®, Kendrion) as PEP in infants during a measles outbreak in Austria, 2019.Methods: After exposure to a highly contagious measles patient, identified infants were evaluated for eligibility for IVIG PEP. Infants were tested for measles maternal antibodies, if the result was expected to be available within 72 h after exposure. IVIG was administered to eligible infants with negative maternal IgG antibody levels (n = 11), infants with protective levels but result beyond 72 h (n = 2) and infants not tested for maternal IgG antibodies (n = 52). Telephone enquiries were made asking for measles infection. Effectiveness was calculated using exact logistic regression. Samples of four out of seven used IVIG batches were tested for MV-neutralizing antibody capacity.Results: In 63 (96.9%) of 65 infants PEP with IVIG was administered. The parents of two infants declined IVIG PEP. None of the infants with IVIG PEP got measles or symptoms suggestive for measles, but both infants who did not receive PEP were infected. Effectiveness of IVIG PEP was calculated to be 99.3% (CI 95%: 88.7–100%). No serious adverse event of IVIG treatment was observed. The investigation on MV-neutralizing antibody capacity showed a geometric mean titer ranging from 10.0 to 12.7 IU/ml, resulting in a 1.57–2.26-fold higher concentration than postulated as minimum level for immunity.Conclusions: Our findings suggest that the used IVIG preparation provided an at least non-inferior protection rate compared to IVIG preparations derived from donors before the global introduction of standard active immunization against measles.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Mauro Boiago ◽  
Carlo Maria Dellino ◽  
Martina Perazzolo Marra ◽  
Luciano Babuin ◽  
Giulia Famoso ◽  
...  

Abstract A 61-year-old man suffering from myasthenia gravis with predominant bulbar involvement since 10 months before admission, was diagnosed with thymoma in April 2021. He had no relevant comorbidities except for history of polymorphic ventricular ectopic beats. In this regard, in 2019 he had undergone transthoracic echocardiogram and coronary computed tomography angiography, which resulted both normal. After 1 month, due to poor response to standard medical therapy with prednisone and pyridostigmine and in preparation for thymectomy, an intravenous immunoglobulins (IVIG) treatment was prescribed leading to mild clinical improvement (Myasthenia Gravis Foundation of America Clinical Classification IIIA—MGFA). Two weeks later, the patient underwent robotic-assisted thoracoscopic thymectomy without complications. Pathological findings were consistent with type B1 Thymoma classified as Masaoka Stage IIB (TNM Stage pT1a). After discharge the patient complained a rapid worsening of neurological symptoms (MGFA IIIB) leading to an urgent hospitalization for Myasthenia Gravis exacerbation in the middle of June. On admission Intravenous Immunoglobulins (IVIG) treatment was immediately started. After administration of the second IVIG dose, he had a myasthenic crisis complicated by refractory heart failure with significant increase of cardiac troponin up to 5.768 ng/L, requiring invasive ventilation, inotropic support and urgent transfer to the Cardiac Intensive Care Unit (CICU). The 2D echo showed severe left ventricular systolic dysfunction (LVEF 20%) with diffuse hypokinesis. The patient underwent cardiac catheterization and coronary angiography that confirmed severe reduction of the LVEF (LVEF 23%) with embolic occlusion of the distal posterior descending coronary artery (PDA) without other significant coronary artery stenosis. An endomyocardial biopsy was performed, which revealed cardiomyocytes of normal dimensions with sporadic cytoplasmic vacuolization and excluded signs of inflammation, fibrosis, necrosis and viral myocarditis. The day after the patient completed IVIG treatment. During the following days, despite persistence of severe left ventricular systolic dysfunction, he was successfully weaned form inotropic and ventilatory support. At neurological evaluation he reported persistence of severe bulbar involvement with upper and lower limbs weakness. Five days later, the patient had a sudden cardiac arrest for pulseless electrical activity. Advanced cardiac life support requiring inotropes and invasive ventilation was performed for 28 min before returning to spontaneous circulation. The echocardiogram excluded pulmonary embolism and mechanical complications but showed severe left ventricular systolic dysfunction. A new coronary angiography showed clear coronary arteries including PDA. Because of severe haemodynamic compromise, an Impella CP device was implanted and set at maximum support level (P8 flow, &gt;3 L/min). A neurological exam revealed no severe neurological sequelae. As a result of the long CPR the patient had a massive left haemothorax, initially treated with multiple blood transfusions and pleural drainage. Two days later, due to persistence of haemodynamic instability and active pleural bleeding with incessant severe anaemia the case underwent a Heart Team discussion where it was decided to escalate Impella CP device to Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) and then perform a video-assisted thoracoscopic evacuation of the haemothorax. Both procedures were carried out without complications. The patient had an immediate haemodynamic improvement which led to rapid weaning from inotropic support. Haemoglobin was stable. The 2D echo showed significant improvement of the LVEF (40%). After 3 days, given the persistence of haemodynamic stability, ECMO device was removed and invasive ventilation stopped shortly afterwards. Eleven days later, another 2D echo demonstrated complete recovery of left ventricular systolic function (LVEF 59%). Notwithstanding, the patient reported a progressive worsening of neurological symptoms with generalized myasthenia and severe bulbar involvement (MGFA IVB) along with episodes of respiratory muscle fatigue requiring non-invasive ventilation. For this reason, the patient was transferred to Subintensive Respiratory Unit and the case underwent a new multidisciplinary discussion involving neurologists, cardiologists and haematologists. Specialists agreed upon potential causal role of IVIG treatment in transient left ventricular dysfunction and considered re-administration absolutely contraindicated. Thus, they prescribed five plasmapheresis treatments and up-titration of corticosteroid therapy (methylprednisolone up to 60 mg od). An immediate and outstanding improvement of neurological symptoms was obtained (MGFA IIIA) and the patient was discharged from hospital 1 week later.


2021 ◽  
Author(s):  
Xue Fan ◽  
Ying Li ◽  
Xin Guo ◽  
Jingjing Lan ◽  
Mingguo Xu

Abstract Background: Kawasaki Disease (KD) is an acute self-limiting systemic vasculitis syndrome which can result in arterial damage especially in coronary artery. To find possible new biomarkers for the diagnosis of KD by Data independent acquisition (DIA) quantitative proteomics.Methods: Twenty-seven patients with KD were enrolled in the present study, further, gingival crevicular fluid of before IVIG treatment with KD was collected as the experimental group. Meanwhile, 18 healthy volunteers were recruited as the control group.DIA quantitative proteomics mass spectrometry analysis was performed on the GCF samples of each group, and the protein expression profiles of the two groups of GCF were detected. Function enrichment of DEP by KEGG and GO, protein-protein interaction (PPI) analysis for all the DEPs detected, Finally, the multiple reaction monitoring mass spectrometry method was used to verify the selected DEPs.Results:197 DEPs (174 up-regulated and 23 down-regulated) were detected in the CGF between the KD group and the normal control group. Cellular process and metabolic process, binding and catalytic activity are the most altered biological process and molecular function, respectively. NOD−like receptor signaling pathway, Protein processing in endoplasmic reticulum pathway and influenza pathway are most significant pathway. EIF2AK2, B2M and GBP1 are kernel proteins in PPI network. The results of MRM-MS of 12 DEPs including IFIT3, UB2L6, HP, A1AT, HSP90AA1, HNRPC, HSP90AB1, SAA1, MX1, B2M, FKBP4 and TRAP1 were highly consistent with DIA.Conclusions: We suggested that 12 proteins in GCF could be used as new biomarkers for early diagnosis of KD. We also found that KD is closely related to gingival inflammation at the molecular level, which provides new ideas and directions for the diagnosis and treatment of KD.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1142
Author(s):  
Takafumi Kubota ◽  
Takafumi Hasegawa ◽  
Kensuke Ikeda ◽  
Masashi Aoki

Neurological complications following vaccinations are extremely rare, but cannot be eliminated. Here, we report the first case of unilateral oculomotor nerve palsy (ONP) with anti-GQ1b antibody after receiving the Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine. A 65-year-old man developed diplopia and ptosis in the right eye 17 days after vaccination, without preceding infection. Neurological examination revealed mild blepharoptosis, limitation of adduction, and vertical gaze on the right side. Increased levels of anti-GQ1b ganglioside antibody in the serum and albuminocytologic dissociation in the cerebrospinal fluid were detected. Cranial magnetic resonance imaging showed swelling and enhancement of the right oculomotor nerve. The patient was diagnosed with right ONP accompanied with anti-GQ1b antibody, and intravenous immunoglobulin (IVIG) therapy for 5 days was administered. The limitation of adduction and vertical gaze improved, and ptosis markedly resolved after IVIG treatment. Given the temporal sequence of disease progression, laboratory findings, and a favorable response to IVIG, a causal relationship cannot be ruled out between the occurrence of ONP and COVID-19 immunization. Since immunomodulatory treatments significantly hasten the recovery and minimize the residual symptoms in anti-GQ1b antibody syndrome, clinicians should be aware of this clinical condition following COVID-19 vaccination.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1062-1062
Author(s):  
Melissa Ge ◽  
Danyal Ladha ◽  
Jennifer Lymer ◽  
Stefana Pancic ◽  
Marc Carrier ◽  
...  

Abstract Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults &gt;18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results : Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT); and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to &gt;44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67; D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. Figure 1 Figure 1. Disclosures Carrier: Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria; Aspen: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria. Castellucci: BMS: Honoraria; Pfizer: Honoraria; Amag Pharmaceuticals: Honoraria; The Academy: Honoraria.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2140-2140
Author(s):  
Evangelia Vlachodimtropoulou Koumoutsea ◽  
Tsz Kin Lo ◽  
Clarissa Bambao ◽  
Greg Denomme ◽  
Gareth Seaward ◽  
...  

Abstract OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed &lt; 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on 'Statistical Package for Social Science Version 16.0' (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses &lt;20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple "top-up" transfusion, and six (35%) phototherapy. CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


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