Journal Article Commercial enzyme-linked immunosorbent assay for neopterin detection in blood donations compared with RIA and HPLC Get access P Mayersbach, P Mayersbach Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar R Augustin, R Augustin Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar H Schennach, H Schennach Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar D Schönitzer, D Schönitzer Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar E R Werner, E R Werner Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar H Wachter, H Wachter Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar G Reibnegger G Reibnegger Centr. Inst. Blood Transfusion and Immunol., Univ. Hospital, Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 40, Issue 2, 1 February 1994, Pages 265–266, https://doi.org/10.1093/clinchem/40.2.265 Published: 01 February 1994

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) further enhances the effect of IFN-gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN-gamma and TNF-alpha are involved inhibiting hematopoiesis.

Neopterin concentrations in body fluids of HIV-1 seropositives provide predictive information. In 1986, we examined serum and urine neopterin concentrations in 29 HIV-1 seropositives. Serum levels of soluble IL-2 receptor (sIL2R), soluble CD8 (sCD8), tumour necrosis factor alpha (TNF-α) and circulating immune complexes (CIC) were retrospectively analysed in 1989. All individuals had increased serum and urine neopterin, sIL2R and CIC concentrations, 2729 had increased sCD8 concentrations, whereas all had normal TNF-α levels. During a 3-year follow-up, high urine and serum neopterin concentrations were significantly associated with progression to AIDS and with the occurrence of AIDS-associated death. Both neopterin variables were of similar predictive value (p < 0.001, generalized Wilcoxon test). sIL2R concentrations were of borderline significance in predicting the onset of AIDS (p = 0.05). All other parameters lacked predictive information in our study. We conclude, that chronic immune activation is detectable in almost all HIV-1 seropositives. Chronic immune activation may be associated with HIV-1 replication and may contribute to the immunopathology of HIV-1 infection.

To the Editor.— Human immunodeficiency virus (HIV) seroconversion has occurred in three health care workers who have been exposed to blood but not via needle-stick injury.1 It is now well established that activation of T lymphocytes regulates HIV reproduction. It is likely that macrophages activated with gamma interferon contribute to HIV production also. We have concluded that activation of T lymphocytes by foreign or modified histocompatibility complex determinants represents a crucial event in HIV infection.2,3We have demonstrated a high frequency of elevated neopterin levels in all high-incidence groups for acquired immunodeficiency syndrome (AIDS), even in HIV-seronegative individuals.2Since neopterin is produced specifically from human macrophages on stimulation with gamma interferon, we concluded that early steps in the activation cascade of cellular immunity are induced in those individuals.4Moreover, this status was found to parallel progressive HIV infection, eg, patients with AIDS have the highest neopterin

Elevated neopterin levels are indicative of activation of the cellular immune system. Studies on excretion of neopterin in patients with AIDS and ARC, as well as in members of risk groups have demonstrated repeated or permanent stimulation of the immune system. This stimulation can be observed in all risk groups independent of LAV/HTLV-III infection. Additionally, in vitro replication of LAV/HTLV-III has been observed to be quantitatively greatest in activated CD4+-lymphocytes. Hence, we conclude that activation of the cellular immune system represents the central cofactor for progressive LAV/HTLV-III infection. These findings seem to contrast with most reports in the literature to date, but observations of other authors corroborate them. As consequence of these studies, therapeutic regimens using immunostimulatory strategies should be prevented in AIDS and ARC patients. Immunosuppressive treatment should be considered.