Correlation of ribonucleic acid polymerase chain reaction, acid dissociated p24 antigen, and neopterin with progression of disease. A retrospective, longitudinal study of vertically acquired human immunodeficiency virus type 1 infection in children.

OBJECTIVE: We investigated the relationship between cell-free viral load, neopterin, age-adjusted CD4+ cell concentration, and clinical events in 49 children with vertically acquired human immunodeficiency virus type 1 infection. STUDY DESIGN: Viral load was measured by quantitating viral ribonucleic acid in serum by polymerase chain reaction and measurement of immune complex dissociated p24 antigen in serum and plasma. Children were followed for an average of 2 1/2 years, with an average of 6 samples per child. Medical records were reviewed for weight, CD4+ cell count and clinical events. RESULTS: High virus copy number in serum was predictive of a decrease in weight-for-age zscore during the subsequent 6 months. High viral load, low CD4+ cell count, and high neopterin level were correlated with encephalopathy. High viral load correlated with opportunistic infections. All of these relationships held regardless of treatment status, although viral load decreased significantly after treatment was begun. CONCLUSIONS: Measurements of viral load were useful prognostic indicators for poor weight gain. Elevated serum virus levels and neopterin values and low CD4+ cell counts were all associated with encephalopathy.

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.

Cervical intraepithelial neoplasia is not associated with elevated serum neopterin levels.

Neopterin, a marker of cellular immune activation, was elevated in patients who had cervical cancer in previous studies. To examine neopterin in the presence of precursors to cervical cancer (i.e., cervical intraepithelial neoplasia) we measured serum levels in 185 colposcopy patients in Jamaica, a country with high cervical cancer incidence, and in 72 age-matched Jamaican women selected from a large population-based sample. We also measured serum levels of beta-2-microglobulin, another commonly used marker of immune activation. Neopterin and beta-2-microglobulin levels were not elevated in colposcopy patients; neither were they related to severity of cervical neoplasia. In multivariable analysis, neither adjustments for detection of cervical human papillomavirus DNA by PCR nor detection of antibodies to human T-cell lymphotropic virus type I (a retrovirus endemic to Jamaica) altered our findings. The absence of a serologically detectable increase in cellular immune activation linked to cervical intraepithelial neoplasia suggests that the immunological response to cervical intraepithelial neoplasia does not involve substantial systemic cellular immune activation.

Is neopterin - a marker of cellmediated immune response - helpful in classifying leprosy?

The urinary excretion of neopterin, an indicator of cellular immune response, was measured in patients suffering from leprosy. No difference was found between the BT+T group and BL + L group. All age groups presented with similar urinary neopterin excretion. There was no correlation apparent batween the duration of disease and urinary neopterin excretion. Whether the most recent skin smear was positive or negative, did not make any difference. Similary, prior medication did not play any role in influencing urinary neopterin excretion. Urinary neopterin excretion is of little value in classifying leprosy, but it might be of some value in long-term follow-up and in determining the activity of the disease and the efficacy of therapy.