Autoantibodies to IL-17A may be Correlated with the Severity of Mucocutaneous Candidiasis in APECED Patients

The relative roles of various autoantibodies against IL-17-type cytokines in susceptibility to chronic mucocutaneous candidiasis (CMC) in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) remain poorly defined. The purpose of this longitudinal study was to analyze the relationship between the occurrence of mucocutaneous candidiasis and levels of anti-IL-17A, anti-IL-17F and anti-IL-22 autoantibodies. We studied six APECED patients from four families with various disease manifestations. Clinical data were collected during regular follow-up. Anti-endocrine organ antibody levels and clinical chemistry and immunology parameters were determined in routine laboratory assays on freshly isolated serum. Levels of autoantibodies against IL-17A, IL-17F, IL-22, IFN-α, IFN-ω and TNF-α, and cytokine release by Candida-exposed blood cells were determined by ELISA. Mutations were analyzed by sequencing genomic DNA. Four patients carried the germline c.769C?>?T homozygous nonsense mutation, which results in R257X truncation of the AIRE protein, and two patients from the same family were compound heterozygous for the c.769C?>?T/c.1344delC mutation. We found persistently high levels of antibodies against IL-17A in the serum samples of one patient presenting CMC since infancy and low or undetectable anti-IL-17A antibody levels in the sera of five patients with no candidiasis or without severe candidiasis. By contrast, levels of autoantibodies against IL-17F and IL-22 were higher in all patients than in healthy controls. Release of IL-17-type cytokines by Candida-exposed blood mononuclear cells was low or negligible in all patients tested. We suggest that anti-IL-17A antibodies may play an important role in the predisposition to candidiasis of APECED patients. However, the lack of severe CMC in APECED patients with high levels of IL-17F and anti-IL-22 autoantibodies clearly calls into question the role of these antibodies as the principal cause of cutaneous and mucosal candidiasis in at least some APECED patients. These data also suggest that the impaired release of IL-17-type cytokines by blood cells may be an element of the immunopathology of CMC in APECED patients.     

Risk Factors for Esophageal Candidiasis in a Large Cohort of HIV-Infected Patients Treated with Nucleoside Analogues

 To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using 1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral therapy in HIV-infected patients) and who had no previous history of EC. During a median follow-up period of 19 months, 87 (6%) patients developed EC. The results of the cohort study showed an increased risk of EC associated with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P<0.0001) and prior zidovudine therapy (P=0.02) at entry to the study. The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell count (P<0.0002), recent antibacterial chemotherapy (P=0.01) and oral candidiasis (P<0.05). Cotrimoxazole prophylaxis also increased the risk of EC (P=0.04) in the case-control study.     

伴或不伴慢性胃炎的抑郁症患者抗抑郁疗效分析

目的 探讨伴或不伴慢性胃炎的抑郁症病人在抗抑郁疗效上的区别。方法 住院抑郁症病人治疗前经胃镜检查，分为研究组(伴有慢性胃炎)和对照组(未见胃粘膜改变)，在抗抑郁治疗前后分别作SCL-90和HAMD评定，结果统计分析。结果 两组病人在抗抑郁治疗前后有关抑郁程度的评定如HAMD、SCL-90中的抑郁因子分的组间比较差异均无显著性，但在治疗后的SCL-90的躯体化和焦虑因子上，研究组和对照组的差异有显著性。结论 伴慢性胃炎的抑郁症病人经抗抑郁治疗后与不伴慢性胃炎者的抑郁程度的改变较一致，但前者比后者较易遗留躯体化和焦虑等问题。     

Spotlight on Eptifibatide in Patients with Acute Coronary Syndromes and/or Undergoing Percutaneous Coronary Intervention

Eptifibatide (Integrilin) is a highly specific, reversible, intravenously administered glycoprotein IIb/IIIa receptor antagonist that acts at the final common step of the platelet aggregation pathway. Data from large clinical trials indicate that intravenous eptifibatide as adjunctive therapy to standard care is effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI). In the ESPRIT (Enhanced Suppression of the Platelet glycoprotein IIb/IIIa Receptor with Integrilin Therapy) trial in patients undergoing PCI with stenting, eptifibatide, compared with placebo, achieved significant reductions in death and ischemic complications and was better than a strategy of reserving treatment for the bailout situation. In the large PURSUIT (Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial in patients with NSTE ACS, eptifibatide was associated with a significant reduction in the incidence of death or myocardial infarction (MI) compared with placebo. Eptifibatide is well tolerated in these trials. Ongoing trials are currently investigating the efficacy and tolerability of regimens that include this agent in other indications, including ST-segment elevation MI.     

No Indication for a Defect in Toll-Like Receptor Signaling in Patients with Hyper-IgE Syndrome

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-γ, IL-2, and TNF-α producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-α, IL-6, IL-10, IFN-α, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.     

Multiple Mycoplasmal Infections Detected in Blood of Patients with Chronic Fatigue Syndrome and/or Fibromyalgia Syndrome

 The aim of this study was to investigate the presence of different mycoplasmal species in blood samples from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection. In this study, patients with chronic fatigue syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans, Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic polymerase chain reaction. Among these mycoplasma-positive patients, infections were detected with Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% and triple infections in 22%, but only when one of the species was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.     

IL-10、IFN-γ在外阴阴道念珠菌病患者发病中的作用

目的检测白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）在正常女性、外阴阴道念珠菌病及复发性外阴阴道念珠菌病阴道分泌物中的表达水平。探讨细胞因子IL-10和IFN-γ的表达水平与外阴阴道念珠菌病发病的关系。方法ELISA法检测初发组和复发组念珠菌性阴道炎的妇女阴道分泌物中IL-10、IFN-γ的表达水平,以健康体检妇女为对照组。结果初发和复发念珠菌性阴道炎的阴道分泌物中IL-10的表达水平均显著高于对照组,复发组较初发组的表达水平也有显著性差异（P〈0．05）;初发和复发念珠菌性阴道炎的阴道分泌物中IFN-γ的表达水平元显著性差异（P〉0．05）,但均高于健康对照组（P〈0．05）。结论Th1型和Th2型细胞因子的表达异常可能与念珠菌性阴道炎发病和复发有关。     

Microbiological Analysis of Nontyphoidal Salmonella Strains Causing Distinct Syndromes of Bacteremia or Enteritis in HIV/AIDS Patients in San Diego,California

Recurrent invasive nontyphoidal Salmonella (NTS) infection is an AIDS-defining illness that has become less common in the developed world in the era of highly active antiretroviral therapy (HAART), while it has emerged as a major public health problem in developing countries, particularly sub-Saharan Africa. We retrospectively analyzed Salmonella (NTS) infection in HIV/AIDS patients from June 2003 until December 2009 at the University of California, San Diego (UCSD), Medical Center. Bacterial isolates from all patients were tested for selected microbiological properties, including major Salmonella (NTS) virulence loci rpoS, sodCI, spvB, and sseI. Fourteen percent of all Salmonella (NTS) cases recorded at the UCSD Medical Center during this period occurred in known HIV/AIDS patients. The clinical presentations in HIV patients fell into two distinct groups, bacteremia and enteritis. There was little clinical overlap between these two syndromes. All strains were positive for the presence of the rpoS and sodCI virulence loci, and 75% of strains were positive for the presence of the spvB and sseI loci. Antibiotic susceptibility assay showed that all strains were susceptible to trimethoprim-sulfamethoxazole and ciprofloxacin. The clinical presentation did not have a clear relationship to the CD4⁺ cell count. Of the bacteremic isolates, all but one isolate, drawn from a patient with substantial enteric comorbidities, had all of the virulence genes tested, but 66% of nonbacteremic, enteritis strains also contained all the tested virulence loci. In conclusion, neither patients'' CD4⁺ cell count nor bacterial strain properties necessarily predicted the clinical presentation of HIV/AIDS patients with Salmonella (NTS) infection, and AIDS patients can have episodes of Salmonella enteritis without dissemination.     

慢性丙型肝炎患者自身抗体的检测分析

采用荧光抗体间接法（ＩＦＡ）对３９例慢性丙型肝炎患者血清进行了自身抗体检测。结果显示慢活肝（ＣＡＨ）抗核抗体（ＡＮＡ）和抗平滑肌抗体（ＳＭＡ）检出率均高于健康人（Ｐ＜０．０５，Ｐ＜０．０１）。自身抗体阳性的慢性丙型肝炎患者血清转氨酶显著高于自身抗体阴性患者。因此认为自身免疫可能是丙型肝炎病毒（ＨＣＶ）慢性感染后肝组织损伤的重要因素。     

Study of p53 in Elderly Patients with Myelodysplastic Syndromes by Immunohistochemistry and DNA Analysis

We analyzed the tumor suppressor gene product, p53, in elderly patients with myelodysplastic syndromes (MDS) and in overt leukemia patients after transformation from MDS using immunohistochemical techniques. We examined 52 MDS patients (mean age 79 years, range 68 to 96) from the time of initial diagnosis to death or development of overt leukemia. p53 protein was detected by immunohistochemistry (IHC) in 8/52 patients (15%) at initial diagnosis: 1/26 with refractory anemia (RA), 0/4 with RA with ringed sideroblasts, 3/11 with RA with an excess of blasts (RAEB), 3/8 with RAEB in transformation, and 1/3 with chronic myelomonocytic leukemia. We also analyzed gene mutations in patients with positive IHC. p53 mutations were detected in 3/8 (38%) patients. IHC-positive patients had a significantly higher incidence of leukemic transformation and the presence of a complex karyotype with monosomy 17. IHC-positive cells included blasts as well as mature myeloid cells, erythroblasts, and megakaryocytes. Scrutiny of our data in combination with previous data revealed that patients with positive IHC in multilineage cells were older than those in whom positivity was noted mostly in myeloblasts. This suggests that p53 IHC positivity with a multilineage pattern may be a characteristic of MDS in older patients.