Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.     

Glucocorticosteroid treatment for cerebrospinal fluid eosinophilia in a patient with ventriculoperitonial shunt.

BACKGROUND: Cerebrospinal fluid (CSF) eosinophilia commonly occurs in patients with ventriculoperitoneal (VP) shunts and is associated with shunt complications such as obstruction or infection. Glucocorticosteroids (GCS) are effective in reducing eosinophilia and eosinophils in skin, nasal mucosa, and airway epithelium. Effects of GCS on CSF eosinophils has not been reported. OBJECTIVE: To demonstrate glucocorticosteroid effects on the CSF eosinophil levels and to propose that GCS may be used as a therapeutic agent for CSF eosinophilia. RESULT: A case report of a patient with congenital hydrocephalus and a VP shunt developed CSF eosinophilia associated with latex allergy and shunt malfunction. Daily treatment with 2 mg/kg of methylprednisolone was associated with reduced peripheral eosinophilia and slightly reduced CSF eosinophil counts. Pulse methylprednisolone, 15 mg/kg, was associated with complete reduction of CSF eosinophils and prolonged VP shunt survival. CONCLUSION: Systemic glucocorticosteroids effectively reduce CSF eosinophils. Glucocorticosteroids may be beneficial for treatment of CSF eosinophilia associated with VP shunt malfunction.     

The immunologic workup of the child suspected of immunodeficiency.

OBJECTIVE: This review is intended to provide an outline for the evaluation of patients suspected of having immunodeficiency, a problem that is frequently encountered in clinical practice. DATA SOURCES: Information was obtained through a MEDLINE literature search as well as from standard textbooks in immunology. Also included is information that reflects the authors' clinical experience in the field. RESULTS: In general clinical practice, many physicians feel inadequate to evaluate patients with suspected immune deficiencies. They also think that the process of evaluation is time-consuming, which results in misdiagnosis of a substantial percentage of such disorders. Hence, the prevalence of immunodeficiency disorders is much higher than generally thought. At present, there are >80 unique primary immunodeficiency conditions and >50 syndromes that are associated with various immunologic defects. The prevalence of secondary immunodeficiency has also been increasing because of the tragic epidemic of HIV infection, more usage of immunosuppressive medications and bone marrow stem cell transplantation, and the severe degree of malnutrition in underdeveloped countries. It is necessary for clinicians, particularly the specialists in allergy and immunology, to be able to evaluate the status of the immune system. CONCLUSIONS: Very valuable information can be gathered from the medical history and physical examination that may exclude or increase the suspicion of immunologic defect. Laboratory tests can then be appropriately selected to define the specific defect. Once the diagnosis has been settled, proper medical management can be instituted with subsequent improvement in morbidity and mortality of such disorders.     

Different mechanisms are utilized by HIV-1 Nef and staphylococcal enterotoxin A to control and regulate interleukin-10 production

Interleukin-10 (IL-10) plays an important immunopathogenic role in immunologic diseases, especially in HIV infection and atopic dermatitis. The control and regulatory mechanisms of IL-10 production have not been described in these diseases. Recently, we demonstrated that HIV-1 Nef induces IL-10 production in monocytes and that staphylococcal enterotoxin A (SEA) induces IL-10 production in T-lymphocytes. Here we show that Nef-induced IL-10 production and mRNA expression are strongly blocked by rapamycin, but are not blocked by cyclosporin (CsA) or FK506. Conversely, we show that CsA and FK506 completely inhibit SEA-induced IL-10 protein production and mRNA expression. The results of this study demonstrate that IL-10 production by Nef and SEA is controlled and regulated by different mechanisms.     

Validation of current joint American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology guidelines for antibody response to the 23-valent pneumococcal vaccine using a population of HIV-infected children

BACKGROUND: Measuring antibody responses to 23-valent pneumococcal polysaccharide vaccines (PPV) is crucial to evaluation of humoral immune function. However, data are limited comparing responses in immunodeficient subjects. OBJECTIVE: A case-controlled study comparing changes in PPV antibody titer in immunocompetent and immunodeficient children was performed to validate current guidelines. METHODS: A cohort of 95 immunocompetent children and 22 HIV-infected children, ages 2 to 15 years, was vaccinated with PPV, and before and after vaccination, IgG titers against capsular polysaccharides for 12 pneumococcal serotypes were measured. Results were used to calculate the receiver operator characteristic curve, sensitivity, and specificity of various interpretation criteria for their accuracy in detecting suboptimal responders. RESULTS: Immunodeficient subjects had lower CD4%, antidiphtheria, antitetanus titers, and mean post-PPV titers (2.5 +/- 1.7 vs 4.5 +/- 2.1 mug/mL; P < .001) compared with immunocompetent subjects. The interpretation, using individual post-PPV titer of > or =4-fold increase over prevaccination as a positive response, yielded the highest accuracy as measured by area under the curve value (receiver operator characteristic curve = .755). For this criterion, the numbers of serotypes with positive responses of < or =5 of 12 serotypes measured yielded 72.7% sensitivity and 56.8% specificity in detecting antibody-deficient subjects. CONCLUSION: Current guidelines using > or =4-fold increase in post-PPV titers has sufficient sensitivity and specificity to identify antibody deficiency. The minimal positive responses should be at least 50% of serotypes tested. CLINICAL IMPLICATIONS: Measurement of PPV antibody response based on the current guidelines accurately identify children with humoral immunodeficiency.     

LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells

Background  

Co-infections of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. Tb) are steadily increasing and represent a major health crisis in many developing countries. Both pathogens individually stimulate tumor necrosis factor-alpha (TNF) release from infected cells and TNF, in turn, enhances the replication of each. A recent report on a Phase I clinical trial suggested that etanercept (soluble TNF receptor) might be beneficial in treating HIV/M. Tb co-infected patients. We sought to determine if a small molecule inhibitor of TNF synthesis and activity could block replication of either organism and thus be a potential adjunct to existing drugs targeting these agents.     

Improving care of HIV-infected patients in the outpatient setting with patient data flow sheets.

Medical management of pediatric/adolescent HIV has become increasingly complex, requiring a multidisciplinary approach to care. Close clinical monitoring is needed to minimize opportunistic infections, initiate appropriate antiretroviral therapy, and ensure optimal health care to the patient. Monitoring should include evaluation of efficacy and side effects of therapy, early detection and treatment of HIV-associated complications, and maintenance of current immunizations. Tracking clinical data in chronically ill patients is a difficult task without an effective monitoring system. A patient data flow sheet was created to assist in planning care and monitoring disease progression by consolidating clinical information into an organized, one-page summary for each patient. One year after the patient data flow sheets were instituted, there was a significant improvement in the consistency of obtaining and monitoring routine HIV labs as well as serologies, and other recommended tests. The flow sheets have increased effectiveness of patient care and have been used to assist with quality assurance monitoring and quality improvement in the clinic setting.