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Suke Xing,1,2 Hui Zhang,2 Ye Qiu,3 Mianluan Pan,1 Wen Zeng,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Comprehensive Internal Medicine, the Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Jianquan Zhang, Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, Guangdong, People’s Republic of China, Tel +8613978123845, Fax +86755-23482484, Email jqzhang2002@126.comPurpose: To summarize the clinical characteristics, treatment and outcomes of transplant recipients infected with Talaromyces marneffei (TM).Materials and Methods: A retrospective analysis was performed on 2 patients with Talaromycosis marneffei (TSM) and transplants at the First Affiliated Hospital of Guangxi Medical University, and a systematic literature review was conducted simultaneously.Results: This article reported two patients after kidney transplantation who developed fever, cough within 3– 4 months. Their haemoglobin was decreased. Their chest computed tomography (CT) showed nodules. TM was detected in their blood or bronchoalveolar lavage fluid samples by next-generation sequencing (NGS). After antifungal treatment with voriconazole (VOR), one patient worsened, the other patient died. A total of 21 patients with TSM after transplants were reported in the literature review. Fourteen underwent kidney transplantation, 4 underwent liver transplantation, 2 underwent lung transplantation, and 1 underwent bone marrow transplantation. The median time from initiating the postoperative immunosuppressive therapy to the onset of symptoms or disease changes was 18 (0.5– 140) months. Among them, 9 patients developed fever, 7 patients developed cough or expectoration and 4 patients developed dyspnoea. Haemoglobin was decreased in 10 patients. Pulmonary nodules were found in 7 patients. Among the 21 patients, 7 were diagnosed by positive culture, 6 by biopsy, 5 by culture and biopsy. Of the 21 patients, 13 patients improved by antifungal therapy, 8 patients worsened or died. Seven patients who received amphotericin B followed by itraconazole (ITR) therapy all improved. Regarding the use of immunosuppressants in 12 patients, 9 patients had to discontinue or reduce their medications (6 patients improved, 3 patients worsened or died).Conclusion: Patients with TSM after transplant often have disseminated infections, involving the respiratory, hematopoietic and so on. Fever, cough, decreased haemoglobin and pulmonary nodules often occur approximately 18 months after surgery. The combined applications of culture, biopsy, NGS are helpful for an early diagnosis. Antifungal therapy with amphotericin B followed by itraconazole is recommended, and the dosage of the immunosuppressant should be adjusted timely.Keywords: Talaromyces marneffei, Talaromycosis marneffei, transplant recipients, immunosuppressants, antifungal drug

Mengxin Tang,1,2,* Mianluan Pan,1,* Ye Qiu,1 Jie Huang,3 Wen Zeng,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Tuberculosis Ward, Nanning Fourth People’s Hospital, Nanning, Guangxi, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Zeng, Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel +8618589883694, Fax +86771-5350031, Email guigao0302@163.com Jianquan Zhang, Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China, Tel +8613978123845, Fax +86755-23482484, Email jqzhang2002@126.comBackground: Anti-IFN-γ autoantibodies (AIGAs) are closely related to the disseminated infection of multiple pathogens. Mycobacterium phlei (M. phlei) is a nonpathogenic nontuberculous mycobacteria (NTM), and M. phlei infection of the bone is extremely rare. We report a rare case of high-titer AIGAs presenting with Sweet’s syndrome (SS) accompanied by opportunistic coinfection with multiple pathogens during 12 years of follow-up. The patient in this case also developed disseminated M. phlei infection with osteolytic destruction after treatment for SS.Case Presentation: A 68-year-old Chinese woman was admitted to our hospital in August 2009 due to fever and cough with expectoration for 3 months. The patient was successively infected with Klebsiella pneumoniae, herpes zoster virus and Candida. Chest computed tomography (CT) showed recurrent consolidations in different lung fields. After 15 months of antimicrobial treatment, the patient experienced partial recovery. In September 2010, the patient was pathologically diagnosed with SS due to the presence of multiple rashes. After prednisone and thalidomide treatment, the rashes subsided, and the pulmonary lesions had completely absorbed. In May 2011, the patient was diagnosed with disseminated tuberculosis and was administered anti-tuberculosis therapy for 3 months without improvement. NTM was subsequently cultured from her sputum and chest wall pus, and she improved after 20 months of anti-NTM therapy. In March 2016, the patient developed osteolytic destruction of the C7-T2 vertebral bodies with a back abscess. NTM was eventually cultured from the dorsal abscess pus and further identified as M. phlei. High-titer AIGAs were detected in the patient’s serum. After another round of aggressive anti-NTM therapy, the patient was finally cured.Conclusion: Patients with AIGA-associated anti-cytokine autoantibody disease can present with multiple opportunistic infections and SS involving the lung. AIGA-associated immunodeficiency leads to infection with nonpathogenic M. phlei, which is refractory, can cause relapse, and even leads to osteolytic destruction.Keywords: Mycobacterium phlei, sweet’s syndrome, osteolytic destruction, anti-IFN-γ autoantibodies

Jingshan Wei,1 Ye Qiu,1 Wen Zeng,1 Mianluan Pan,1 Jianquan Zhang1,2 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, Pepole’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518033, Pepole’s Republic of ChinaCorrespondence: Jianquan ZhangDepartment of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518033, Pepole’s Republic of ChinaTel +86 139 7812 3845Fax +86 0771 535 0031Email jqzhang2002@126.comPurpose: Talaromyces marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported.Methods: We reported two SLE patients infected by T. marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis.Results: Eleven patients with SLE infected with T. marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died.Conclusion: T. marneffeiinfection should be excluded when SLE patients, especially if on long-term immunosuppressants, present withfever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes ofSLE patients withT. marneffeiinfection.Keywords: Talaromyces marneffei, systemic lupus erythematosus, immunosuppressant

Additional file 1. Detailed methods for Anti-IFN-�� autoantibody assay, Bio-Plex��� 25 cytokine assay, flow cytometry, DNA extraction, DNA libraries and sequencing, and bioinformatics analysis are provided in Additional file.

Wen Zeng,1,2 Ye Qiu,1,2 Mengxin Tang,1,2 Hui Zhang,2 Mianluan Pan,1 Shudan Tang,2 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Jianquan ZhangDepartment of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of ChinaTel +8613978123845Fax +86755-23482484Email jqzhang2002@126.comAbstract: A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces marneffei and Burkholderia cepacia infection. The patient’s lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections.Keywords: Burkholderia cepacia, Talaromyces marneffei, adult immunodeficiency, neutralizing anti-interferon-γ autoantibodies