Structure-activity relationship studies of pyrogallol as a calcineurin/NFAT signaling suppressor.

Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC50 value of 82.6 µM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol.

Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules' physical properties and neurite morphology.

The physical properties of cytoskeletal microtubules have a multifaceted effect on the expression of their cellular functions. A superfamily of microtubule-associated proteins, MAP2, MAP4, and tau, promote the polymerization of microtubules, stabilize the formed microtubules, and affect the physical properties of microtubules. Here, we show differences in the effects of these three MAPs on the physical properties of microtubules. When microtubule-binding domain fragments of MAP2, tau, and three MAP4 isoforms were added to microtubules in vitro and observed by fluorescence microscopy, tau-bound microtubules showed a straighter morphology than the microtubules bound by MAP2 and the three MAP4 isoforms. Flexural rigidity was evaluated by the shape of the teardrop pattern formed when microtubules were placed in a hydrodynamic flow, revealing that tau-bound microtubules were the least flexible. When full-length MAPs fused with EGFP were expressed in human neuroblastoma (SH-SY5Y) cells, the microtubules in apical regions of protrusions expressing tau were straighter than in cells expressing MAP2 and MAP4. On the other hand, the protrusions of tau-expressing cells had the fewest branches. These results suggest that the properties of microtubules, which are regulated by MAPs, contribute to the morphogenesis of neurites.

High-dose IgG suppresses local inflammation and facilitates functional recovery after olfactory system injury.

OBJECTIVE: Head trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti-inflammatory treatment using steroids or anti-cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high-dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. METHODS: Olfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. High-dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X-gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test. RESULTS: High-dose IgG-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG-injected mice. INTERPRETATION: These findings suggest that high-dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

A clinical survey on patients with taste disorders in Japan: A comparative study.

OBJECTIVE: To investigate changes in the clinical state of taste disorders between 1990, 2003, and 2019 using the same methodology as that in previous studies. MATERIALS AND METHODS: In June 2019, we mailed a questionnaire to 1100 otolaryngologists belonging to the Japan Society of Stomato-pharyngology and investigated three question categories: "Institution", "Number of patients for 3 months", and "Treatment". In addition, we analyzed some results by the class of institution. RESULTS: The rate of patients who complained of taste disorders in the 2019 survey (220/100,000 persons/year) was twice that of the 1990 survey (110/100,000 persons/year), and slightly higher than that of the 2003 survey (192/100,000 persons/year). The rate of female patients was higher than that of male patients in all age groups. The number of patients was correlated with age up to 70 years of age in both genders. The rates of performing taste tests to assess taste function in the 2019 survey were significantly decreased compared with a 2003 survey (electrogustometry: p<0.001, filter paper disk method: p<0.05 in university). The rate of examination of the serum zinc in the 2019 survey was increased compared with the 1990 survey (p<0.001). Zinc oral therapy was used for the treatment of taste disorders in 239/299 (79.9%) patients/institutes for 3 months. In addition, 213 institutions (69.6%) answered that zinc oral therapy was efficacious for taste disorders. CONCLUSION: The patients who complained of taste disorder have increased. The zinc administration is an appropriate clinical treatment for taste disorders in Japan. To enhance treatment for taste disorders, simpler methods for assessing taste function need to be developed, and the pathological mechanisms of taste disorders other than zinc deficiency need to be clarified.

Successful treatment with nivolumab in a patient with lung adenocarcinoma complicated by pulmonary aspergilloma.

Immune checkpoint inhibitors (ICIs) are the key drugs used in patients with non-small cell lung cancer (NSCLC). However, anti-PD-1 therapy might worsen chronic infection by reactivating the immune response to infectious diseases. Here, we describe a case of successful treatment with nivolumab in a patient with NSCLC complicated by pulmonary aspergilloma, which was safely treated by surgical resection before administration of nivolumab. In conclusion, to safely treat patients with locally limited chronic pulmonary aspergillosis (CPA), surgical resection should be considered before ICI therapy.

Microtubule elongation along actin filaments induced by microtubule-associated protein 4 contributes to the formation of cellular protrusions.

Actin-microtubule crosstalk is implicated in the formation of cellular protrusions, but the mechanism remains unclear. In this study, we examined the regulation of cell protrusion involving a ubiquitously expressed microtubule-associated protein (MAP) 4, and its superfamily proteins, neuronal MAP2 and tau. Fluorescence microscopy revealed that these MAPs bound to F-actin and microtubules simultaneously, and formed F-actin/microtubule hybrid bundles. The hybrid bundle-forming activity was in the order of MAP2 > MAP4 ≫ tau. Interestingly, the microtubule assembly-promoting activity of MAP4 and MAP2, but not of tau, was upregulated by their interaction with F-actin. When MAP4 was overexpressed in NG108-15 cells, the number of cell processes and maximum process length of each cell increased significantly by 28% and 30%, respectively. Super-resolution microscopy revealed that 95% of microtubules in cell processes colocalized with F-actin, and MAP4 was always found in their vicinity. These results suggest that microtubule elongation along F-actin induced by MAP4 contributes to the formation of cellular protrusions. Since MAP4, MAP2 and tau had different crosstalk activity between F-actin and microtubules, it is likely that the functional differentiation of these MAPs is a driving force for neural evolution, causing significant changes in cell morphology.

Relationships among bronchodilator reversibility, the fraction of exhaled nitric oxide, and the parameters of the forced oscillation technique in adult asthma treated with inhaled corticosteroids and long-acting ß2 agonists combination.

In bronchial asthma, both airway inflammation and reversible airway narrowing require assessment and treatment. These two pathologies are treated primarily with inhaled corticosteroids (ICS) and long-acting ß2 agonists (LABA), respectively. Therefore, ICS-LABA combinations are widely used to treat asthma. Airway inflammation and reversible airway narrowing are assessed primarily with fraction of exhaled nitric oxide (FENO) and bronchodilator reversibility (BDR). The forced oscillation technique (FOT) has recently attracted attention as a method for assessing obstructive respiratory disturbance. However, little is known about the relationships among these assessments. Therefore, we investigated the relationships among BDR, FENO, and FOT during ICS-LABA combination therapy. The subjects comprised 87 patients (25 men and 62 women) with asthma undergoing ICS/LABA combination therapy from July to September 2017. We applied the FENO test, FOT, and BDR testing without the patients stopping their therapy. The rates of change in FEV1 (ΔFEV1%) was correlated with FENO (r = 0.278). Among the FOT parameters, X5 (r = -0.263), Fres (r = 0.292), and AX (r = 0.245) were significantly correlated with ΔFEV1%. FENO, Fres and %FEV1 at baseline in these stable asthmatics were significantly assosiated with ΔFEV1% independently of the effects of age, atopy and body mass index (BMI). These results suggest that FENO and the results of respiratory function testing and FOT reflect different aspects of asthma and should be combined and comprehensively evaluated.

Continued administration of pembrolizumab for adenocarcinoma of the lung after the onset of fulminant type 1 diabetes mellitus as an immune-related adverse effect: A case report.

A 61-year-old woman with stage IVA lung adenocarcinoma exhibited high PD-L1 expression. Pembrolizumab was administered as second-line therapy. She developed destructive thyroiditis and her thyroid function started to decline during the administration of three to five courses. She was subsequently diagnosed with fulminant type 1 diabetes mellitus and ketoacidosis during the eighth course and insulin treatment was initiated. Pembrolizumab remained effective and was continued for 21 courses, even after the onset of diabetes mellitus. Immune-checkpoint inhibitor treatment can be continued with hormone replacement even after the development of type 1 diabetes mellitus as an immune-related adverse event.

[A CASE OF BRONCHIAL ASTHMA ASSOCIATED WITH BRONCHIOLAR EOSINOPHILIA AND TREATED WITH MEPOLIZUMAB].

A 68 year-old woman with dyspnea and cough had been treated with inhaled corticosteroids for X-15 years, but her symptoms worsened in X year. High-resolution chest CT revealed small centrilobular nodules in the right upper lobe in March X year. The patient was diagnosed with asthma and diffuse panbronchiolitis and treated with inhaled corticosteroids, a long-acting beta agonist, and clarithromycin, but her condition did not improve and her peripheral blood eosinophil count increased. In August X year, we performed a transbronchial biopsy of the right upper lung. Histopathological examination revealed eosinophilia in the bronchial secretions and mild nonspecific inflammatory changes. The diagnosis was bronchial asthma associated with bronchiolitis. The patient was treated successfully with mepolizumab.

Three Cases of Idiopathic Diffuse Pulmonary Ossification.

Diffuse pulmonary ossification (DPO) is an uncommon diffuse lung disease characterized by metaplastic bone formation in the lung parenchyma and is rarely diagnosed in life. While DPO usually occurs as a secondary disease, idiopathic cases are extremely rare. We describe three cases of idiopathic DPO, two of which were definitively diagnosed by surgical lung biopsy. One case was observed in a 43-year-old man with a history of recurrent pneumothorax who developed pneumothorax after the surgical biopsy. Few reports have described cases of DPO with recurrent pneumothorax; however, pneumothorax should be considered as a potential complication when such patients are encountered.

Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis.

As expression level of allergic disease-sensitive genes are correlated with allergic symptom severity, suppression of these gene expressions could be good therapeutics. We have demonstrated that PKCδ signaling and NFAT signaling, involve in histamine H1 receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018.

Hyperprogressive disease in patients with non-small cell lung cancer treated with nivolumab: A case series.

BACKGROUND: Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy. Four patients were treated with corticosteroids to overcome their symptomatic events. Nivolumab exhibited efficacy after temporal progression, so-called "pseudoprogression", in three patients, and their symptoms and laboratory results improved. In the other patient, pleural and pericardial effusions increased after nivolumab therapy, and drainage was required, with no subsequent recurrence. The clinical courses of our case series indicate that alternative treatment, namely high-dose corticosteroids, antibiotics, and drainage, effectively treated the symptoms of rapid tumor progression. Of note, corticosteroids suppressed the temporary inflammatory reaction to nivolumab. Although hyperprogressive disease is thought to be associated with poor quality of life and survival, these treatment strategies may be useful in patients with expected responses to immunotherapy.

Dyspnea and the Varying Pathophysiologic Manifestations of Chronic Obstructive Pulmonary Disease Evaluated by Cardiopulmonary Exercise Testing With Arterial Blood Analysis.

Background: Patients with chronic obstructive pulmonary disease (COPD) show varying mechanisms of exertional dyspnea with different exercise capacities. Methods: To investigate the pathophysiologic conditions related to exertional dyspnea, 294 COPD patients were evaluated using cardiopulmonary exercise testing (CPET) with arterial blood analyses, with the patients classified into two groups according to their exercise limitation: the leg fatigue group (n = 58) and the dyspnea group (n = 215). The dyspnea group was further subdivided into four groups based on peak oxygen uptake ( V ° O 2 in mL/min/kg): group A (< 11), group B (11 to < 15), group C (15 to < 21), and group D (≥21). Results: In the dyspnea group, group A (n = 28) showed the following findings: (i) the forced expiratory volume in 1 s was not correlated with the peak V ° O 2 (p = 0.288), (ii) the arterial oxygen tension (PaO2) slope (peak minus resting PaO2/Δ V ° O 2 ) was the steepest (p < 0.0001) among all subgroups, (iii) reduced tidal volume (VT) was negatively correlated with respiratory frequency at peak exercise (p < 0.0001), and (iv) a break point in exertional VT curve was determined in 17 (61%) patients in group A. In these patients, there was a significant negative correlation between bicarbonate ion ( HCO 3 - ) levels at peak exercise and VT level when the VT-break point occurred (p = 0.032). In group D (n = 46), HCO 3 - levels were negatively correlated with plasma lactate levels (p < 0.0001). In all subgroups, the HCO 3 - level was negatively correlated with minute ventilation. The dyspnea subgroups showed no significant differences in the overall mean pH [7.363 (SD 0.039)] and Borg scale scores [7.4 (SD, 2.3)] at peak exercise. Conclusions: During exercise, ventilation is stimulated to avoid arterial blood acidosis and hypoxemia, but ventilatory stimulation is restricted in the setting of reduced respiratory system ability. These conditions provoke the exertional dyspnea in COPD. Although symptom levels were similar, the exertional pathophysiologic conditions differed according to residual exercise performance; moreover, COPD patients showed great inter-individual variability. An adequate understanding of individual pathophysiologic conditions using CPET is essential for proper management of COPD patients.

Post-progression survival after cessation of treatment with nivolumab for advanced non-small cell lung cancer: A retrospective study.

OBJECTIVES: The effectiveness of treatment after cessation of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) has not been well investigated. The aim of the present study was to clarify the clinical benefit of post-nivolumab treatment in such patients. MATERIALS AND METHODS: A retrospective review was conducted on patients who received treatment after cessation of nivolumab due to disease progression or adverse events at the Toneyama National Hospital between January 2016 and April 2017. RESULTS: Among 64 patients treated with nivolumab, 26 patients received treatment after cessation of nivolumab due to disease progression (n = 21) or adverse events (n = 5). The median age of the patients was 68 years and 19 patients were male. Nineteen patients had performance status (PS) 1 or less at initiation of post-nivolumab treatment. Four, 20, and 2 patients were treated with platinum doublets, a single agent, and molecular targeting agents, respectively. Response rate, disease control rate, and median progression-free survival of first-line post-nivolumab treatment were 34.6% (9 patients), 73.1% (19 patients), and 2.8 months (95% confidence interval [CI]: 1.7-5.2), respectively. Adverse events (≥ grade 3) and treatment cessation were observed in 57.7% (15 patients) and 19.2% (5 patients), respectively. There were no statistically significant differences for the majority of patient characteristics between the groups with (n = 26) and without post-nivolumab treatment. However, PS at cessation of nivolumab and post-progression survival (PPS) after cessation of nivolumab (median PPS: 12.6 vs. 1.4 months, 95% CI: 3.8-14.7 vs. 0.4-2.2) were significantly different between the groups. A multivariate Cox regression analysis showed significant correlation of PS at cessation of nivolumab (hazard ratio [HR]: 0.34, 95% CI: 0.13-0.87) and post-nivolumab treatment (HR: 0.19, 95% CI: 0.08-0.43) with prolonged PPS after nivolumab. CONCLUSION: Median post-progression survival in patients with advanced NSCLC who received post-nivolumab treatment was approximately 1 year.

Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury.

BACKGROUND: Refractory olfactory dysfunction is a common finding in head trauma due to olfactory nerve injury. Anti-inflammatory treatment using steroids is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that steroids can induce side effects. The present study examines if the inhibition of proinflammatory cytokine, high mobility group box 1 (HMGB1), can facilitate olfactory functional recovery following injury. METHODS: Olfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. We measured HMGB1 gene expression in the olfactory bulb using semi-quantitative polymerase chain reaction (PCR) assays and examined HMGB1 protein localization in the olfactory bulb using immunohistochemical staining. Anti-HMGB1 antibody was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X-gal staining labeled OMP in the degenerating and regenerating olfactory nerve fibers, and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using both an olfactory avoidance behavioral test and evoked potential recording. RESULTS: HMGB1 gene and protein were significantly expressed in the olfactory bulb 12 h after NTx. Anti-HMGB1 antibody-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia and an increase in regenerating nerve fibers. Both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in the anti-HMGB1 antibody-injected mice. CONCLUSIONS: These findings suggest that inhibition of HMGB1 could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

Two cases of response to pembrolizumab in epidermal growth factor receptor mutated lung adenocarcinoma patients with programmed death-ligand 1 overexpression.

Recently, the immune checkpoint inhibitor (ICI) pembrolizumab was demonstrated to be superior to platinum doublet chemotherapy in the first-line setting in patients with tumor programmed death-ligand 1 (PD-L1) expression of at least 50%. However, because patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were not included in that study, the efficacy of pembrolizumab in lung cancers carrying EGFR mutations could not be determined. Here we describe two cases of response to pembrolizumab in EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression. These cases indicate that ICI is an effective treatment for EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression.

Successful use of linezolid for refractory Mycobacterium abcessus infection: A case report.

A 51-year-old male patient was receiving treatment for Mycobacterium abscessus infection for approximately 10 years. However, as his condition gradually progressed to type II respiratory insufficiency, he was referred to our hospital, which was near his home. Computed tomography on his first visit revealed an abscess in the right lower lobe. Because respiratory insufficiency was evident, he was admitted the same day. We began treatment with meropenem, amikacin, and clarithromycin, but his symptoms did not improve. In accordance with the 2007 American Thoracic Society/Infectious Diseases Society of America statement, we administered linezolid, which resulted in gradual improvement in his physical status and imaging findings.

Endoscopic electrocauterization of pyriform sinus fistula.

To determine the efficacy of endoscopic electrocauterization for pyriform sinus fistula (PSF) using a flexible Bugbee cautery electrode. From 2009 to 2016, a total of eight patients with acute suppurative thyroiditis or cervical abscess secondary to PSF were retrospectively registered in our study (three males, five females; median age 6.5 years). All patients underwent endoscopic electrocauterization as treatment for PSF. Six of eight patients had no recurrence after the initial endoscopic electrocauterization of PSF. One patient with recurrence developed symptoms 9 days after cauterization and another experienced recurrence after 2 years. Mean follow-up for the eight patients was 50 months (range 5-96 months). No post-operative complication was reported. Endoscopic electrocauterization appears to be a less-invasive, safe, and effective method for the treatment of PSF.

Pulmonary rehabilitation for COPD improves exercise time rather than exercise tolerance: effects and mechanisms.

BACKGROUND: COPD patients undergoing pulmonary rehabilitation (PR) show various responses. The purpose of this study was to investigate the possible mechanisms and predictors of the response to PR in COPD patients. METHODS: Thirty-six stable COPD patients underwent PR including a 4-week high-intensity exercise training program, and they were evaluated by cardiopulmonary exercise testing. All patients (mean age 69 years, severe and very severe COPD 94%) were classified into four groups by whether the exercise time (Tex) or the peak oxygen uptake [Formula: see text] increased after PR: two factors increased (both the Tex and the peak [Formula: see text] increased); two factors decreased; time only increased (the Tex increased, but the peak [Formula: see text] economized); and [Formula: see text] only increased (the Tex decreased, but the peak [Formula: see text] increased). Within all patients, the relationships between baseline variables and the post-to-pre-change ratio of the time-slope, Tex/(peak minus resting [Formula: see text]), were investigated. RESULTS: Compared with the two factors increased group (n=11), in the time only increased group (n=18), the mean differences from pre-PR at peak exercise in 1) minute ventilation [Formula: see text] (P=0.004), [Formula: see text] (P<0.0001), and carbon dioxide output [Formula: see text] (P<0.0001) were lower, 2) [Formula: see text]/ [Formula: see text] (P=0.034) and [Formula: see text]/ [Formula: see text] (P=0.006) were higher, and 3) the dead space/tidal volume ratio (VD/VT) and the dyspnea level were similar. After PR, there was no significant difference in the ratio of the observed peak heart rate (HR) to the predicted peak HR (220 - age [years]) between the two groups. A significant negative correlation with the baseline time-slope (r=-0.496, P=0.002) and a positive correlation with the baseline body mass index (BMI) (r=0.496, P=0.002) were obtained. CONCLUSIONS: PR in COPD patients improves Tex rather than exercise tolerance, economizing oxygen requirements, resulting in reduced ventilatory requirements without cardiac loads followed by reduced exertional dyspnea. In addition, the time-slope and BMI could be used to predict PR responses beforehand.

Levels of Antibody against Glycopeptidolipid Core as a Marker for Monitoring Treatment Response in Mycobacterium avium Complex Pulmonary Disease: a Prospective Cohort Study.

The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) is sometimes complicated and time-consuming. A serodiagnostic kit that measures the serum levels of IgA antibodies against the glycopeptidolipid (GPL) core is commercially available and has good diagnostic accuracy for MAC-PD. However, the significance of measurement of GPL core IgA antibody levels in monitoring for chemotherapy response in patients with MAC-PD was not well investigated. Thirty-four treatment naive MAC-PD patients who were started on multidrug chemotherapy were enrolled. Their antibody levels were prospectively measured at regular intervals. The relationships between their antibody levels and the therapeutic outcomes were examined. The patients were classified into three groups (conversion, recurrence, and nonconversion) based on the bacteriological outcomes after chemotherapy. There were no significant differences in the antibody levels before treatment between the culture conversion (n = 19), recurrence (n = 7), and nonconversion (n = 8) groups (P = 0.9881). The levels decreased significantly after the chemotherapy (P < 0.0001). Recurrence and/or worsening of chest radiography findings were observed in cases whose antibody levels subsequently increased after cessation of the chemotherapy. No significant difference in the percent decrease in antibody levels by the chemotherapy was observed between the culture conversion and recurrence groups (P = 0.9338). The initial antibody levels are not a predictor of therapeutic outcomes, and also the percent decrease in antibody levels is not a sufficient indicator of the cessation of chemotherapy. However, serial measurements of antibody levels may allow objective monitoring of disease activity in individual MAC-PD patients.