Publications by authors named "Zuotao Zhao"

22 Publications

  • Page 1 of 1

Effects of pregnancy on chronic urticaria: Results of the PREG-CU UCARE study.

Allergy 2021 May 22. Epub 2021 May 22.

Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Urticaria Center of Reference and Excellence (UCARE), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown.

Aim: To analyze the course and features of CU during and after pregnancy.

Patients And Methods: PREG-CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47-item questionnaire completed by CU patients, who became pregnant within the last 3 years.

Results: A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively.

Conclusions: These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.
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http://dx.doi.org/10.1111/all.14950DOI Listing
May 2021

Practical algorithm to inform clinical decision-making in the topical treatment of atopic dermatitis.

J Dermatol 2021 May 7. Epub 2021 May 7.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Diseases, Beijing, China.

Atopic dermatitis is a chronic relapsing, inflammatory skin disorder associated with skin barrier dysfunction, the prevalence of which has increased dramatically in developing countries. In this article, we propose a treatment algorithm for patients with mild-to-moderate and severe atopic dermatitis flares in daily clinical practice. An international panel of 15 dermatology and allergy experts from eight countries was formed to develop a practical algorithm for the treatment of patients with atopic dermatitis, with a particular focus on topical therapies. In cases of mild-to-moderate atopic dermatitis involving sensitive skin areas, the topical calcineurin inhibitor pimecrolimus should be applied twice daily at the first signs of atopic dermatitis. For other body locations, patients should apply a topical calcineurin inhibitor, either pimecrolimus or tacrolimus, twice daily at the first signs of atopic dermatitis, such as pruritus, or twice weekly in previously affected skin areas. Emollients should be used regularly. Patients experiencing acute atopic dermatitis flares in sensitive skin areas should apply a topical corticosteroid twice daily or alternate once-daily topical corticosteroid/topical calcineurin inhibitor until symptoms improve. Following improvement, topical corticosteroid therapy should be discontinued and patients switched to a topical calcineurin inhibitor. Maintenance therapy should include the use of pimecrolimus once daily for sensitive areas and tacrolimus for other body locations. This treatment algorithm can help guide clinical decision-making in the treatment of atopic dermatitis.
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http://dx.doi.org/10.1111/1346-8138.15921DOI Listing
May 2021

The Diagnosis and Management of Allergic Reactions Caused by Chinese Materia Medica.

Clin Rev Allergy Immunol 2021 Feb 19. Epub 2021 Feb 19.

Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, VA, USA.

Traditional Chinese medicines (TCM) have been used in China for thousands of years. Although TCM has been generally perceived to be safe, adverse reactions to Chinese materia medica (CMM) have been reported. Most of the adverse reactions are allergic in nature, but other mechanisms may play a role. This review focuses on the mechanism and clinical presentation of these allergic reactions. Allergic reactions can occur as a result of the active and inactive ingredients of CMM. Impurities and chemicals generated during the production process can also lead to allergic or adverse reactions. Environmental factors such as temperature, humidity, and light can cause changes in the allergenicity of drugs. Human error in formulating CMM drugs also contributes to adverse drug reactions. The management of allergic reactions to CMM includes taking a good history, avoidance of medications in the same class as those which caused prior reactions, the proper training of staff, adherence to manufacturer guidelines and expiration dates, evaluation of benefit and risk balance, and the formulation of a risk management strategy for the use of CMM. A small test dose of a considered drug before using, improvements in drug purification technology, and proper storage and clinical administration help reduce allergic reactions due to CMM.
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http://dx.doi.org/10.1007/s12016-020-08812-7DOI Listing
February 2021

Omalizumab treatment and outcomes in Chinese patients with chronic spontaneous urticaria, chronic inducible urticaria, or both.

World Allergy Organ J 2021 Jan 5;14(1):100501. Epub 2021 Jan 5.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China.

Background: Chronic urticaria (CU) is a common skin disorder, which can be further divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is effective and safe for difficult-to-treat CSU based on clinical trials. However, there are limited data comparing the therapeutic effect of omalizumab for patients with CSU, CIndU, and CSU plus CIndU. Meanwhile, there is still no reliable predictor for treatment response or relapse. Our study was conducted to collect real-world clinical data on omalizumab treatment in patients with CSU, CIndU, and both.

Methods: This was an observational, retrospective chart review of patients with CU initiating omalizumab treatment between February 2018 and May 2020 (maximum 28 months follow-up).

Results: A total of 138 patients were included, 87 with CSU alone, 33 with different forms of CIndU, and 18 with both. A total of 87.0% (n = 120/138) of the CU patients responded to omalizumab therapy, among which 65.2% (n = 90/138) of the patients showed complete response and 21.7% (n = 30/138) of the patients showed partial response. The therapeutic effect and speed of onset of effect for omalizumab were comparable among patients with CSU, CIndU, or both. Autologous serum skin test (ASST)-positive patients were more likely to show a slow response to omalizumab therapy (  = 0.043). Non-responders had lower baseline total IgE levels (35.0 vs 121.5 kU/L,  < 0.001). The proportion of patients with low total IgE levels in non-responders was significantly higher than that of responders (61.1% vs. 14.5%,  < 0.001). Also, more non-responder patients had elevated thyroid autoantibodies than responders (50.0% vs. 23.0%,  = 0.041). The median ratio of serum IgG-anti-TPO to serum total IgE in non-responders was significantly higher compared with responders (1.22 vs. 0.09,  < 0.001). Non-responders also had shorter treatment periods (4.5 vs 6.0 months,  = 0.035) compared with responders. Two of 3 patients (67.4%, n = 29/43) experienced relapse after ceasing omalizumab therapy. These patients had longer disease durations (52.0 vs. 15.0 months,  = 0.007) and higher baseline total IgE levels (179.9 vs. 72.5 kU/L,  = 0.020) than patients who did not relapse. We reinitiated omalizumab treatment for 10 relapsed patients, all of them reported a rapid response after the first injection within the first 4 weeks of retreatment.

Conclusion: Omalizumab is highly effective in patients with difficult-to-treat CSU, CIndU, or both. Responders tend to have unique immunological features and longer treatment periods. Patients with higher baseline total IgE levels and longer disease durations are more likely to experience rapid relapse after discontinuation of omalizumab.
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http://dx.doi.org/10.1016/j.waojou.2020.100501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804987PMC
January 2021

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Skin Mast Cells Contribute to Infection.

Front Immunol 2020 19;11:469. Epub 2020 Mar 19.

Department of Dermatology, First Hospital, Peking University, Beijing, China.

(), a dimorphic fungus, causes sporotrichosis. Mast cells (MCs) have been described to be involved in skin fungal infections. The role of MCs in cutaneous sporotrichosis remains largely unknown. To characterize the role and relevance of MCs in cutaneous sporotrichosis. We analyzed cutaneous sporotrichosis in wild-type (WT) mice and two different MC-deficient strains. , MCs were assessed for -induced cytokine production and degranulation after incubation with . We also explored the role of MCs in human cutaneous sporotrichosis. WT mice developed markedly larger skin lesions than MC-deficient mice (> 1.5 fold) after infection with , with significantly increased fungal burden. induced the release of tumor necrosis factor alpha (TNF), interleukin (IL)-6, IL-10, and IL-1β by MCs, but not degranulation. induced larger skin lesions and higher release of IL-6 and TNF by MCs as compared to the less virulent . In patients with sporotrichosis, TNF and IL-6 were increased in skin lesions, and markedly elevated levels in the serum were linked to disease activity. These findings suggest that cutaneous MCs contribute to skin sporotrichosis by releasing cytokines such as TNF and IL-6.
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http://dx.doi.org/10.3389/fimmu.2020.00469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096480PMC
March 2021

The complex role of mast cells in fungal infections.

Exp Dermatol 2019 07 22;28(7):749-755. Epub 2019 Mar 22.

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

In addition to their critical role in allergic disorders, mast cells (MCs) are well recognized for their protective effector functions during bacteria and parasite infections. This review describes recent advancements of our understanding of the complex role of MCs in fungal infections. Specifically, we outline key features of the contribution of MCs to infections with six fungal pathogens, namely Sporothrix, Paracoccidioides, Aspergillus, Malassezia, Candida and Dermatophytes. Evidence from studies of these pathogens suggests that MCs can function as positive regulators that detect and contain fungi at the site of infection. However, it appears that the inflammation induced by MCs following fungal infections may not always and only be beneficial to the host. MC responses during fungal infections may primarily benefit the pathogen by facilitating its spreading and contributing to a greater severity of fungal infections. This review also highlights key drivers of MCs activation and effector mechanisms that have been identified for the multidimensional function of MCs in fungal diseases and in allergic diseases combined with fungal infection.
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http://dx.doi.org/10.1111/exd.13907DOI Listing
July 2019

Ordinary vibratory angioedema is not generally associated with ADGRE2 mutation.

J Allergy Clin Immunol 2019 03 14;143(3):1246-1248.e4. Epub 2018 Nov 14.

Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin, Berlin, Germany.

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http://dx.doi.org/10.1016/j.jaci.2018.10.049DOI Listing
March 2019

Using IFN-γ antibodies to identify the pathogens of fungal rhinosinusitis: A novel immunohistochemical approach.

Mol Med Rep 2018 Mar 27;17(3):3627-3632. Epub 2017 Dec 27.

Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.

Fungal rhinosinusitis (FRS) is commonly caused by various Aspergillus species (spp) and Mucorales fungi, and the treatment and prognosis of cases differ depending on the causative fungus. The present study describes a novel immunohistochemical method that has high sensitivity and specificity for distinguishing between these two types of fungi in patients with FRS. Three groups were included in the study. Group A included formalin‑fixed paraffin‑embedded blocks of 51 nasal tissue specimens of patients with FRS (27 Aspergillus spp and 24 Mucorales) that were continuously obtained from the Department of Pathology of Tongren Hospital in Beijing as the experimental group and 34 cultures (26 Aspergillus spp and 8 Mucorales) of FRS that were randomly selected from the bacterial laboratory of Tongren Hospital in Beijing to verify the staining results of the paraffin‑embedded blocks. Formalin‑fixed paraffin‑embedded blocks of 10 esophageal cancer specimens were included in Group B as the positive control group. All specimens in Groups A and B were stained with interferon‑γ (IFN‑γ) antibody. Group C consisted of the same specimens as described in Group A, however, when performing the immunohistochemical assay, IFN‑γ antibody was replaced by PBS and this served as the negative control group. The differences in IFN‑γ immunohistochemical staining between Aspergillus spp and Mucorales were analyzed. Staining of IFN‑γ in paraffin‑embedded samples was positive in 92.6% (25/27) of specimens in which Aspergillus spp were the causative pathogen, which was significantly higher compared with specimens in which Mucorales was causative (P<0.001), with only 4.2% (1/24) of specimens staining positive for IFN‑γ. Immunohistochemical staining of cell cultures was 100% positive for Aspergillus spp, whereas all Mucorales were negative. Thus, the results of the current study indicated that IFN‑γ antibody immunohistochemical staining may be used as a novel diagnostic tool to distinguish between Aspergillus spp and Mucorales when identifying the causative agent in FRS, providing a useful supplementary test to the current immunohistochemical methods in the clinical diagnosis of FRS.
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http://dx.doi.org/10.3892/mmr.2017.8359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802167PMC
March 2018

Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation.

Cell Biol Toxicol 2017 08 2;33(4):389-405. Epub 2017 Feb 2.

Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, L-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.
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http://dx.doi.org/10.1007/s10565-016-9379-0DOI Listing
August 2017

High diversity of airborne fungi in the hospital environment as revealed by meta-sequencing-based microbiome analysis.

Sci Rep 2017 01 3;7:39606. Epub 2017 Jan 3.

Department of Hospital Infection Control and Management, Beijing Hospital, Beijing, The People's Republic of China.

Invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. In particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. To identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and DNA sequencing analysis with the Illumina MiSeq and HiSeq 2000 sequencing systems. Few bacteria were grown after cultivation in blood agar. However, using microbiome sequencing, the relative abundance of fungi, Archaea species, bacteria and viruses was determined. The distribution characteristics of fungi were investigated using heat map analysis of four departments, including the Respiratory Intensive Care Unit, Intensive Care Unit, Emergency Room and Outpatient Department. The prevalence of Aspergillus among fungi was the highest at the species level, approximately 17% to 61%, and the prevalence of Aspergillus fumigatus among Aspergillus species was from 34% to 50% in the four departments. Draft genomes of microorganisms isolated from the hospital environment were obtained by sequence analysis, indicating that investigation into the diversity of airborne fungi may provide reliable results for hospital infection control and surveillance.
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http://dx.doi.org/10.1038/srep39606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206710PMC
January 2017

Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus.

Arch Dermatol Res 2016 Oct 9;308(8):553-61. Epub 2016 Jul 9.

Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China.

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4(+) T cells, CD8(+) T cells, CD56(+) T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.
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http://dx.doi.org/10.1007/s00403-016-1665-4DOI Listing
October 2016

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database--the quality controlled standard tool for routine identification of human and animal pathogenic fungi.

Med Mycol 2015 May 22;53(4):313-37. Epub 2015 Mar 22.

Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia.

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.
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http://dx.doi.org/10.1093/mmy/myv008DOI Listing
May 2015

A novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.

BMC Infect Dis 2014 Dec 20;14:3856. Epub 2014 Dec 20.

Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China.

Background: Acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. Knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. Therefore, the objectives of this study were to create a rat model of acute invasive fungal rhinosinusitis based on analyzing the impact of different fungal concentrations on establishing infection, and to observe the changes of mast cells in rats with this disease.

Methods: Sprague-Dawley rats were divided randomly into four groups, three of which were experimental and received different concentrations of Aspergillus fumigatus inoculations, and one was a control group (D). The inoculated Aspergillus fumigatus concentrations were 5 × 10(7) conidia/ml in group A, 10(7) conidia/ml in group B, and 10(6) conidia/ml in group C. Before fungal inoculation, rats were immunosuppressed using cyclophosphamide and cortisone acetate, and had Merocel sponges inserted into the right nares. Hematology and histopathology investigations were then performed.

Results: An acute invasive fungal rhinosinusitis rat model was established successfully with an incidence rate of 90% in group A, 50% in group B and 10% in group C. Aspergillus fumigatus invasion was observed in 20% of the lungs in group A, but was not seen in the remaining groups. In addition, no fungi invaded the orbital tissue, brains, livers, spleens or kidneys of any rat. Compared with the control set, the total number of mast cells in the experimental groups was not significantly increased, but mast cell degranulation, on the other hand, was only found in infected nasal cavities.

Conclusions: This investigation illustrates that various fungal concentrations have different effects on the incidence of acute invasive fungal rhinosinusitis, and it also demonstrates the feasibility of using this model to study the process of fungal rhinosinusoidal invasion. In addition, the results suggest that mast cells may play a role in the protection of sinuses against acute Aspergillus fumigatus infection and in the clearance of established hyphal masses.
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http://dx.doi.org/10.1186/s12879-014-0713-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297382PMC
December 2014

Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene.

Int J Genomics 2014 17;2014:950903. Epub 2014 Apr 17.

Department of Dermatology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou 215006, China.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.
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http://dx.doi.org/10.1155/2014/950903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016872PMC
May 2014

A Promoter Region Polymorphism in PDCD-1 Gene Is Associated with Risk of Rheumatoid Arthritis in the Han Chinese Population of Southeastern China.

Int J Genomics 2014 3;2014:247637. Epub 2014 Apr 3.

Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Objective. Programmed cell death 1 (PD-1) induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms with the risk of RA among Chinese patients and healthy controls. Methods. Using the PCR-direct sequencing analysis, 4 PDCD-1 SNPs (rs36084323, rs11568821, rs2227982, and rs2227981) were genotyped in 320 RA patients and 309 matched healthy controls. Expression of PD-1 was determined in peripheral blood lymphocytes by flow cytometry and quantitative real-time reverse transcriptase polymerase chain reaction. Results. We observed that the GG genotype of rs36084323 was associated with a increased risk for developing RA (OR 1.70, 95% 1.11-2.61, P = 0.049). Patients carrying G/G genotype displayed an increased mRNA level of PD-1 (P = 0.04) compared with A/A genotype and healthy controls. Meanwhile, patients homozygous for rs36084323 had induced basal PD-1 expression on activated CD4+ T cells. Conclusion. The PDCD-1 polymorphism rs36084323 was significantly associated with RA risk in Han Chinese population. This SNP, which effectively influenced the expression of PD-1, may be a biomarker of early diagnosis of RA and a suitable indicator of utilizing PD-1 inhibitor for treatment of RA.
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http://dx.doi.org/10.1155/2014/247637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996357PMC
May 2014

α-MSH-stimulated tolerogenic dendritic cells induce functional regulatory T cells and ameliorate ongoing skin inflammation.

J Invest Dermatol 2012 Jul 15;132(7):1814-24. Epub 2012 Mar 15.

Department of Dermatology, University of Münster, Münster, Germany.

The neuropeptide α-melanocyte-stimulating hormone (α-MSH) is a well-known mediator of skin pigmentation. More recently, it has been shown that α-MSH also exerts a strong anti-inflammatory and immunosuppressive activity. To elucidate the mechanisms underlying α-MSH-induced immunosuppression, we investigated whether α-MSH affects dendritic cell/T cell communication, as especially this interaction has an important role in the regulation of immune responses. Here, we show that α-MSH, by binding to MC-1R, induced tolerogenic dendritic cells, which were capable of expanding CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in vitro, as well as in vivo. Notably, those α-MSH-induced Tregs were functional as they efficiently inhibited cutaneous contact allergy and ongoing psoriasis-like skin inflammation in mice. Furthermore, α-MSH induced tolerogenic dendritic cells capable of generating functional Tregs in human blood. Interestingly, human Tregs expanded via α-MSH-stimulated dendritic cells suppressed the proliferation and cytokine secretion of pathogenic T-helper-17 (Th17) cells from individuals with psoriasis. Taken together, these data indicate that α-MSH induced immunosuppressive Tregs in vitro and in vivo, which inhibited disease progression in a mouse model of psoriasis-like skin inflammation and suppressed the activation and proliferation of effector T cells from subjects with psoriasis.
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http://dx.doi.org/10.1038/jid.2012.59DOI Listing
July 2012

Simultaneous detection and identification of Aspergillus and mucorales species in tissues collected from patients with fungal rhinosinusitis.

J Clin Microbiol 2011 Apr 16;49(4):1501-7. Epub 2011 Feb 16.

First Hospital, Peking University, Beijing 100034, People's Republic of China.

Rapid detection and differentiation of Aspergillus and Mucorales species in fungal rhinosinusitis diagnosis are desirable, since the clinical management and prognosis associated with the two taxa are fundamentally different. We describe an assay based on a combination of broad-range PCR amplification and reverse line blot hybridization (PCR/RLB) to detect and differentiate the pathogens causing fungal rhinosinusitis, which include five Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, and A. nidulans) and seven Mucorales species (Mucor heimalis, Mucor racemosus, Mucor cercinelloidea, Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, and Absidia corymbifera). The assay was validated with 98 well-characterized clinical isolates and 41 clinical tissue specimens. PCR/RLB showed high sensitivity and specificity, with 100% correct identifications of 98 clinical isolates and no cross-hybridization between the species-specific probes. Results for five control isolates, Candida albicans, Fusarium solani, Scedosporium apiospermum, Penicillium marneffei, and Exophiala verrucosa, were negative as judged by PCR/RLB. The analytical sensitivity of PCR/RLB was found to be 1.8 × 10(-3) ng/μl by 10-fold serial dilution of Aspergillus genomic DNA. The assay identified 35 of 41 (85.4%) clinical specimens, exhibiting a higher sensitivity than fungal culture (22 of 41; 53.7%) and direct sequencing (18 of 41; 43.9%). PCR/RLB similarly showed high specificity, with correct identification 16 of 18 specimens detected by internal transcribed spacer (ITS) sequencing and 16 of 22 detected by fungal culture, but it also has the additional advantage of being able to detect mixed infection in a single clinical specimen. The PCR/RLB assay thus provides a rapid and reliable option for laboratory diagnosis of fungal rhinosinusitis.
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http://dx.doi.org/10.1128/JCM.02262-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122857PMC
April 2011

Molecular serotype identification of Streptococcus agalactiae of bovine origin by multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay.

FEMS Microbiol Lett 2006 Oct;263(2):236-9

Centre for Infectious Diseases and Microbiology, Institute of Clinical Pathology and Medical Research, Westmead, NSW, Australi.

We used a multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay and sequencing of a variable region of the cps cluster to identify serotypes of 140 Streptococcus agalactiae (group B Streptococcus; GBS) isolates from cattle. Only 71 (51%) isolates were typeable using antisera, but molecular serotypes (MS) were assigned to 133 (95%) and 139 (99%) isolates by partial cpsE-cpsF-cpsG sequencing and mPCR/RLB, respectively. Ninety-four isolates (67%) belonged to MS III and most belonged to a molecular serosubtype (msst) III-3, which is uncommon among GBS isolates from humans. Our results demonstrate that cps clusters of bovine GBS differ significantly from those of GBS isolates from humans.
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http://dx.doi.org/10.1111/j.1574-6968.2006.00428.xDOI Listing
October 2006

Reverse line blot assay for direct identification of seven Streptococcus agalactiae major surface protein antigen genes.

Clin Vaccine Immunol 2006 Jan;13(1):145-9

Centre for Infectious Diseases and Microbiology (CIDM), Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Darcy Road, Westmead, New South Wales 2145, Australia.

We developed a multiplex PCR-based reverse line blot hybridization assay (mPCR/RLB) to detect the genes encoding members of the family of variable surface-localized proteins of Streptococcus agalactiae (group B streptococcus [GBS]), namely, Bca (Calpha), Rib, Epsilon (Epsilon/Alp1/Alp5), Alp2, Alp3, and Alp4, and the immunoglobulin A binding protein, Bac (Cbeta). We used the assay to identify these genes in a collection of well-characterized GBS isolates and reference strains. The results showed that mPCR/RLB avoids the common problems of cross-reaction and nontypability associated with protein typing using antisera. It is as sensitive as, but more practical than, separate gene-specific PCRs and would be suitable for large molecular epidemiological studies of GBS.
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http://dx.doi.org/10.1128/CVI.13.1.145-149.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356620PMC
January 2006

Comparison of a 3-set genotyping system with multilocus sequence typing for Streptococcus agalactiae (Group B Streptococcus).

J Clin Microbiol 2005 Sep;43(9):4704-7

Centre for Infectious Diseases and Microbiology (CIDM), Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, New South Wales, Australia.

Group B streptococcus (GBS; Streptococcus agalactiae) is the most common cause of neonatal and obstetric sepsis and is an increasingly important cause of septicemia in elderly individuals and immunocompromised patients. Epidemiological studies of GBS infections require comprehensive typing systems that provide information about variable characteristics, such as antigenic type, virulence, or antibiotic resistance, as well as the "backbone" structure or the genetic lineage of isolates. We have previously described a 3-set genotyping system that identifies the molecular serotype (MS) or molecular serosubtype (msst), the protein gene profile, and the presence of several mobile genetic elements (F. Kong, D. Martin, G. James, and G. L. Gilbert, J. Med. Microbiol. 52:337-344, 2003). In this study, 83 clinical GBS isolates which had been previously studied by multilocus sequence typing (MLST) (N. Jones, J. F. Bohnsack, S. Takahashi, K. A. Oliver, M. S. Chan, F. Kunst, P. Glaser, C. Rusniok, D. W. Crook, R. M. Harding, N. Bisharat, and B. G. Spratt, J. Clin. Microbiol. 41:2530-2536, 2003) were examined by using the 3-set genotyping system. Genotypes were assigned to five isolates that were nontypeable by conventional serotyping. There were 27 "3-set" genotypes, 24 multilocus sequence types (STs), and 35 unique combinations (or strains), of which the 4 most common, msst III-2 (ST-17), msst III-1 (ST-19), Ia-1 (ST-23), and V-1 (ST-1), accounted for more than 60% of isolates. The 83 isolates were grouped into seven clusters, with a good correlation between the multilocus STs and the genotypes. The combination of 3-set genotyping and MLST adds discriminatory power to strain typing of GBS, which will be useful for future studies of the epidemiology and pathogenesis of GBS disease.
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http://dx.doi.org/10.1128/JCM.43.9.4704-4707.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234084PMC
September 2005