The increase of plasma galectin-9 in a patient with insulin allergy: a case report

Allergic reaction to insulin is known to be associated with eosinophilia and hyper IgE. Recent report showed that eosinophilia is related with the increased synthesis of galectin-9 (GAL-9) and osteopontin (OPN). Here, we examined plasma levels of GAL-9 and OPN first time in a case of 65-year old patient with insulin allergy. Insulin aspart & insulin aspart 30 mix were given to the patient and an elevation of the eosinophil count (8440/μl, 17.6 fold) and a moderate increase of IgE (501 U/ml, reference range: 10-350 U/ml), eotaxin-3 (168 pg/ml, 2 fold), histamine (0.95 ng/ml, 5.3 fold) were found 33 days later. The plasma levels of GAL-9 and OPN were 22.5 and 1.7 fold higher than the cut-off point, respectively. After one month cessation of insulin therapy, elevations of the eosinophil count (3,480/μl; 7.3 fold), and OPN (1.4 fold) still occurred but the GAL-9 levels became normal. Therefore, we noted the increases of GAL-9 and OPN in plasma for the first time in a patient with insulin allergy and propose that GAL-9 reflects the conditions of allergy more accurately

Frequent Detection of Anti-Tubercular-Glycolipid-IgG and -IgA Antibodies in Healthcare Workers with Latent Tuberculosis Infection in the Philippines

Anti-tubercular-glycolipid-IgG (TBGL-IgG) and -IgA (TBGL-IgA) antibodies, and the QuantiFERON-TB Gold test (QFT) were compared in healthcare workers (HCWs, n = 31) and asymptomatic human immunodeficiency virus-carriers (HIV-AC, n = 56) in Manila. In HCWs, 48%, 51%, and 19% were positive in QFT, TBGL-IgG, and -IgA, respectively. The TBGL-IgG positivity was significantly higher (P = 0.02) in QFT-positive than QFT-negative HCWs. Both TBGL-IgG- and -IgA-positive cases were only found in QFT-positive HCWs (27%). The plasma IFN-γ levels positively correlated with TBGL-IgA titers (r = 0.74, P = 0.005), but not TBGL-IgG titers in this group, indicating that mucosal immunity is involved in LTBI in immunocompetent individuals. The QFT positivity in HIV-AC was 31% in those with CD4+ cell counts >350/μL and 12.5% in low CD4 group (<350/μL). 59 % and 29% were positive for TBGL-IgG and -IgA, respectively, in HIV-AC, but no association was found between QFT and TBGL assays. TBGL-IgG-positive rates in QFT-positive and QFT-negative HIV-AC were 61% and 58%, and those of TBGL-IgA were 23% and 30%, respectively. The titers of TBGL-IgA were associated with serum IgA (P = 0.02) in HIV-AC. Elevations of TBGL-IgG and -IgA were related to latent tuberculosis infection in HCWs, but careful interpretation is necessary in HIV-AC

Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection

Background: Dengue virus (DENV) infection remains a major public health burden worldwide. Soluble mediators may play a critical role in the pathogenesis of acute DENV infection. Galectin-9 (Gal-9) is a soluble β-galactoside-binding lectin, with multiple immunoregulatory and inflammatory properties. Objective: To investigate plasma Gal-9 levels as a biomarker for DENV infection. Study design: We enrolled 65 DENV infected patients during the 2010 epidemic in the Philippines and measured their plasma Gal-9 and cytokine/chemokine levels, DENV genotypes, and copy number during the critical and recovery phases of illness. Results: During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to healthy or those with non-dengue febrile illness. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464. pg/ml; dengue fever patients (DF): 1407. pg/ml; non-dengue febrile illness: 616. pg/ml; healthy: 196. pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in DF and DHF patients. Gal-9 levels tracked viral load, and were associated with multiple cytokines and chemokines (IL-1α, IL-8, IP-10, and VEGF), including monocyte frequencies and hematologic variables of coagulation. Further discriminant analyses showed that eotaxin, Gal-9, IFN-α2, and MCP-1 could detect 92% of DHF and 79.3% of DF, specifically (P < 0.01). Conclusion: Gal-9 appears to track DENV inflammatory responses, and therefore, it could serve as an important novel biomarker of acute DENV infection and disease severity

Rapid Decline of IFN-γ Spot-Forming Cells in Pleural Lymphocytes during Treatment in a Patient with Suspected Tuberculosis Pleurisy

A differential diagnosis of tuberculosis pleurisy is often difficult. A 48-year-old Japanese man with no previous medical history visited the outpatient department for dyspnea and fever. His chest-XP and laboratory findings, especially high C-reactive protein levels, indicated pleuritis with pleural effusion. Pleural lymphocytes showed high numbers of spot forming responses in interferon gamma release assay (IGRA). Pleural effusion contained high levels of adenosine deaminase and hyaluronic acid, but no Mycobacterium tuberculosis (TB) antigen was detected by culture or polymerase chain reaction (PCR). Although the infectious agent was not detected, the clinical and laboratory findings strongly suggested that he was suffering from tuberculosis pleurisy. After treatment with anti-TB drugs, a rapid decline of spot-forming cells (SFCs) of pleural lymphocyte was observed, despite persistently high levels of other biomarkers and increased pleural lymphocytes. This case demonstrates that an IGRA of pleural lymphocytes would be useful for therapeutic diagnosis for TB pleurisy suspected for TB

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases

Seminar Lessons: Infectious Diseases Associated with and Causing Disaster

Disasters such as the magnitude-9 Great East Japan Earthquake occur periodically. We considered this experience while developing measures against a predicted earthquake in the Nankai Trough. This report includes a summary of 10 disastrous infectious diseases for which a countermeasures seminar was held. Thirty-five speakers from twenty-one organizations performed the lectures. Besides infectious diseases, conference topics also included disaster prevention and mitigation methods. In addition, the development of point-of-care tests, biomarkers for diagnosis, and severity assessments for infectious diseases were introduced, along with epidemics of infectious diseases affected by climate. Of the 28 pathogens that became a hot topic, 17 are viruses, and 14 out of these 17 (82%) are RNA viruses. Of the 10 seminars, the last 2 targeted only COVID-19. It was emphasized that COVID-19 is not just a disaster-related infection but a disaster itself. The first seminar on COVID-19 provided immunological and epidemiological knowledge and commentary on clinical practices. During the second COVID-19 seminar, vaccine development, virological characteristics, treatment of respiratory failure, biomarkers, and human genetic susceptibility for infectious diseases were discussed. Conducting continuous seminars is important for general infectious controls

Seminar Lessons: Infectious Diseases Associated with and Causing Disaster

Disasters such as the magnitude-9 Great East Japan Earthquake occur periodically. We considered this experience while developing measures against a predicted earthquake in the Nankai Trough. This report includes a summary of 10 disastrous infectious diseases for which a countermeasures seminar was held. Thirty-five speakers from twenty-one organizations performed the lectures. Besides infectious diseases, conference topics also included disaster prevention and mitigation methods. In addition, the development of point-of-care tests, biomarkers for diagnosis, and severity assessments for infectious diseases were introduced, along with epidemics of infectious diseases affected by climate. Of the 28 pathogens that became a hot topic, 17 are viruses, and 14 out of these 17 (82%) are RNA viruses. Of the 10 seminars, the last 2 targeted only COVID-19. It was emphasized that COVID-19 is not just a disaster-related infection but a disaster itself. The first seminar on COVID-19 provided immunological and epidemiological knowledge and commentary on clinical practices. During the second COVID-19 seminar, vaccine development, virological characteristics, treatment of respiratory failure, biomarkers, and human genetic susceptibility for infectious diseases were discussed. Conducting continuous seminars is important for general infectious controls