Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils.

BACKGROUND: Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma. OBJECTIVE: To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood. METHODS: IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma. Expression was further confirmed by immunohistochemistry. Functional signaling through the IL-5Rα was evaluated by measurement of IL-5-inducible modulation of neutrophil surface CD62L and IL-5Rα expression. RESULTS: IL-5Rα was consistently present but at a variable magnitude on blood and lung neutrophils. Expression on lung neutrophils was significantly higher than that on blood cells (p"?>P < .001) where their expression was higher in the presence of airway pathogens, especially with respiratory viruses. Increased receptor expression occurred in response to the translocation of preformed receptors from intracellular stores. Receptors were functional as revealed by IL-5-mediated down-regulation of CD62L and the feed-forward up-regulation of reception expression. CONCLUSION: In addition to the expression on eosinophils and basophils, the IL-5Rα is consistently and abundantly expressed on the surface of blood and especially air space neutrophils. These observations support the concept that some of the efficacy of IL-5/IL-5R-targeting biologics observed in asthma may reflect their ability to target neutrophilic air space inflammation.

Proteus empyema as a rare complication from an infected renal cyst, a case report.

BACKGROUND: The most commonly isolated organisms in a parapneumonic effusion include S. pneumoniae, H. influenzae, and S. aureus. If unusual organisms are isolated from the pleural space, further investigation is warranted to locate the primary source. We present a patient with an infected chronic renal cyst found to have an empyema secondary to Proteus mirabilis to highlight the importance of further diagnostic workup when encountering unusual organisms in the pleural space. CASE PRESENTATION: A 40-year-old African-American female, with a past medical history of asthma and sickle cell trait, presented with 5 weeks of upper respiratory tract symptoms and chest pain. A computed tomography angiogram (CTA) of the chest was negative for a pulmonary embolism but revealed a loculated left sided pleural effusion with associated left-lower lobe consolidation. She was started on empiric antibiotics, and a chest tube was inserted with drainage of frank pus. Fluid gram stain was positive for gram negative rods. Intrapleural fibrinolytics were administered for 72 h given the presence of loculations. With no improvement following fibrinolytics, she was taken to the operating room for large bore chest tube placement and left visceral pleura decortication. Pleural fluid cultures speciated to Proteus mirabilis, so further cross-sectional imaging of her abdomen/pelvis was pursued to evaluate for a primary source. A complex cystic lesion in the upper pole of the left kidney that communicated with the ipsilateral diaphragm was identified. Subsequent drainage and culture of the renal cyst was positive for Proteus mirabilis. Given clinical improvement following these interventions she was discharged with an extended course of antibiotics with plans for repeat imaging following completion of treatment. CONCLUSIONS: While cases of Proteus mirabilis empyema have previously been reported as a consequence of conditions such as pyelonephritis, we present, to our knowledge, the first case of a Proteus mirabilis empyema as a consequence of an infected renal cyst communicating with the pleural space. This study highlights that further evaluation with cross-sectional imaging is warranted when unusual organisms are found in the pleural space. Anatomic abnormalities that become apparent on imaging may help elucidate the source of infection.

End-Tidal Carbon Dioxide as a Prognostic Feature in Pulmonary Arterial Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) is characterized in part by increased dead space ventilation, which can be estimated noninvasively at the bedside by measurement of end-tidal CO2 (ETco2). OBJECTIVES: Prior work has demonstrated that ETco2 is lower in patients with PAH than in control patients, but whether ETco2 has prognostic value is unknown. We hypothesized that lower measurements of ETco2 in patients with PAH correlate with worse long-term outcomes. METHODS: Patients with PAH seen in our referral clinic were prospectively recruited for ETco2 measurement between September 2009 and February 2010. Vital status as of July 2015 was documented using medical records and the Social Security Death Index. RESULTS: Eighty-two patients were followed for a median of 60 months. Twenty-six patients died, and two were lost to follow-up. Patients who died were more likely to be older (58.5 ± 14.9 vs. 47.6 ± 12.2 yr; P < 0.05) and to have shorter 6-minute walk distance (296 ± 127 vs. 401 ± 92 m; P < 0.05). Mean ETco2 in survivors was 30.5 ± 4.8 mm Hg, whereas mean ETco2 in patients who died was 27.1 ± 4.2 mm Hg (P = 0.004). After stratification by median baseline ETco2 of 29 mm Hg, survival in each group was analyzed. Patients with lower ETco2 had shorter survival (P = 0.006). Cox regression analysis with ETco2 as a continuous variable revealed the hazard ratio to be 0.88 (95% confidence interval, 0.80-0.97; P = 0.006). In 52 patients with more than one measurement a median of 17 months apart, ETco2 was unchanged. CONCLUSIONS: Our single-center data suggest that lower ETco2 is associated with shorter survival and that ETco2 is stable over time in patients with PAH.

Increased seroreactivity to human T cell lymphoma/leukemia virus-related endogenous sequence-1 Gag peptides in patients with human T cell lymphoma/leukemia virus myelopathy.

Previously, we had shown that although only 8% of patients with large granular lymphocytic leukemia (LGLL) were infected with human T cell lymphoma/leukemia virus (HTLV)-2, almost half had antibodies to HTLV Gag and Env peptides. Herein, we investigated whether this could be due to cross-reactive antibodies to two homologous peptides in the Gag protein of the endogenous retrovirus HTLV-related endogenous sequence-1 (HRES-1). In addition, we had previously shown that patients with HTLV neurodegenerative diseases had increased seroreactivity to homologous HERV-K10 endogenous retrovirus peptides. Hence, in this study we also examined whether these patients had increased seroreactivity to the aforementioned HRES-1 Gag peptides. Sera from 100 volunteer blood donors (VBD), 53 patients with LGLL, 74 subjects with HTLV-1 or 2 infection (58 nonmyelopathy and 16 myelopathy), and 83 patients with multiple sclerosis (MS) were evaluated. The HTLV-positive myelopathy (HAM) patients had a statistically increased prevalence of antibodies to both HRES-1 Gag peptides (81%) vs. the VBD (0%), LGLL patients (13%), and MS patients (1%), and the HTLV-positive nonmyelopathy subjects (21%). The data suggest that cross-reactivity to HRES-1 peptides could be involved in the pathogenesis of HAM. The difference between the VBD and LGLL patients was also statistically significant, also suggesting a possible association in a minority of patients.

Increased seroreactivity to HERV-K10 peptides in patients with HTLV myelopathy.

BACKGROUND: Previously, we had shown that persons infected with human T-cell lymphoma leukemia virus 1 or 2 (HTLV-1 or 2) had an increased prevalence of antibodies to a peptide in the Pol protein of the retrovirus HERV-K10, homologous to a peptide in HTLV gp21 envelope protein. The prevalence rate was higher in those with myelopathy vs. non-myelopathy. We have now extended our observations to a cohort restricted to North America in whom the diagnosis of HTLV myelopathy was rigorously confirmed to also test for reactivity to another HERV-K10 peptide homologous to the HTLV p24 Gag protein. METHODS: Sera from 100 volunteer blood donors (VBD), 53 patients with large granular lymphocytic leukemia (LGLL), 74 subjects with HTLV-1 or 2 infection (58 non-myelopathy and 16 myelopathy) and 83 patients with multiple sclerosis (MS) were evaluated in ELISA assays using the above peptides. RESULTS: The HTLV myelopathy patients had a statistically significant increased prevalence of antibodies to both HERV-K10 peptides (87.5%) vs. the VBD (0%), LGLL patients (0%), MS patients (4.8%), and the HTLV positive non-myelopathy subjects (5.2%). CONCLUSION: The data suggest that immuno-cross-reactivity to HERV-K10 peptides and/or transactivation of HERV-K10 expression by the HTLV Tax protein may be involved in the pathogenesis of HTLV-associated myelopathy/tropical spastic paraparesis and spastic ataxia.

Short communication: no evidence of HTLV-3 and HTLV-4 infection in New York State subjects at risk for retroviral infection.

The primate T-cell lymphoma viruses (PTLV) are divided into six distinct species. The biology and epidemiology of PTLV-1 and PTLV-2 are very well understood. However, that of PTLV-3, 4, 5, and 6 are not. Recently, in Cameroon, three and one humans were shown to be infected with HTLV-3 and HTLV-4, respectively. We undertook a study to ascertain whether any of these two retroviruses were present in the peripheral blood mononuclear cell DNA of New York State subjects deemed at risk for PTLV infection. Samples were analyzed by PTLV-3 and PTLV-4 specific PCR assays from the following human and simian subject types: African-American medical clinic patients; HTLV EIA+, WB indeterminate blood donors; intravenous drug users; patients with leukemia, lymphoma, myelopathy, polymyositis, or AIDS; and African chimpanzees. None of the 1200 subjects was positive for HTLV-3 or 4. The data indicate that, at the time of sample collection, no evidence exists for the dissemination of HTLV-3 or 4 to New York State. Continued epidemiological studies are warranted to explore the worldwide prevalence rates and dissemination patterns of HTLV-3 and 4 infections, and their possible disease associations.