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SERUM NEOPTERIN AND β2-MICROGLOBULIN IN ANTI-HIV POSITIVE BLOOD DONORS
1216 SERUM NEOPTERIN AND &bgr;2-MICROGLOBULIN IN ANTI-HIV POSITIVE BLOOD DONORS
SIR,-Patients with confirmed AIDS or AIDS-related complex have been found to have raised &bgr;2-microglobulin (&bgr;2-M) and neopterin levels.’ The screening of blood donors for HIV antibodies gave us an opportunity to study the early clinical and biological abnormalities in HIV infection. 97 anti-HIV
positive sera (enzyme immunoassay, confirmed by blot) were detected among 125 000 blood donors in Paris. Detailed examination, done within a month of antibody detection, revealed that 67 % were effectively clinically symptomless; 26 % had a lymphadenopathy syndrome and 7% had lesser forms of AIDS. 15 of the 65 symptomless donors had no abnormal laboratory findings such as anaemia and thrombocytopenia. Erythrocyte sedimentation rates were normal, IgG levels were above 16 g/1, and T4 and T8 counts were normal (T4 and T8 ratios above 1). western
and neopterin were measured by radioimmunoassay (Pharmacia and Behring Laboratories, respectively). Levels in anti-HIV positive donors were compared with those in 46 seronegative donors of similar age distribution. Both neopterin and (3Z M were significantly increased in anti-HIV positive donors, irrespective of clinical status and other laboratory findings (table). Even the 15 donors with neither symptoms nor laboratory test abnormalities had significantly increased levels of (32 M and neopterin. There was a correlation between &bgr;2 -M and neopterin (r =0 67); perhaps these increases reflect accelerated turnover of T cells.
P2-M
NEOPTERIN AND
B2-MICROGLOBULIN LEVELS IN ANTI-HIV
NEGATIVE AND POSITIVE BLOOD DONORS
LAD lymphadenopathy syndrome. Results as mean (SD). All means in anti-HIV-positive donors and subgroups significantly greater than means for serognegative donors (p < 0 001; Mann-Whitney rank test). =
Neopterin and &bgr;2-M seem to be early markers of infection by HIV, even in the absence of clinical and biological manifestations of HIV infection. These markers, though non-specific for HIV infection,5,6rise with the appearance of anti-HIV antibodies and before the
lymphocyte counts fall.
Centre National de Transfusion 75015 Pans, France
1. Francioli
Sanguine,
P. LAMBIN H. DESJOBERT M. DEBBIA J. M. FINE J. Y. MULLER
P, Clement F, Vaudois CHU. Beta2 microglobulin and immune-deficiency a homosexual man. N Engl J Med 1982; 307: 1402-03 2 Bhalla RB, Safai B, Pahwa S, Schwartz MK. Beta2 microglobulin as a prognostic marker for development of AIDS. Clin Chem 1985, 31: 1411-12. 3 Wachter H, Fuchs D, Hausen A, et al. Elevated unnary neopterin levels in patients with acquired immunodeficiency syndrome (AIDS) Z Physiol Chem 1983; 364: 1345-46. 4. Abita JP, Cost H, Milstein S, Kaufman S, Saimot G. Urinary neopterin and biopterin levels in patients with AIDS and AIDS related complex. Lancet 1985; ii: 51-52. 5. Cooper EH, Forbes MA, Hambling MH. Serum beta2 microglobulin and C reactive protein concentration in viral infections. J Clin Pathol 1984; 37: 1140-43. 6. Kem P, Rokos H, Dietrich M. Raised serum neopterin levels and imbalances of T lymphocytes subjects in viral diseases, acquired immune deficiency and related lymphadenopathy syndrome. Biomed Pharmacother 1984; 38: 407-11
WHO WILL GET AIDS? to
SIR,—Your Oct 25 editorial asks for factors that might contribute increased susceptibility to HIV infection and HIV-related
disease. In-vitro data show that activation of T cells is the basic event regulating HIV propagation and cell death. Thus measurement of T cell activation in AIDS patients and in risk groups should contribute to our understanding of the pathogenesis and epidemiology of AIDS. A sensitive and specific tool for detecting activation of the T cell/macrophage system is the measurement of neopterin in urine and serum.’ Neopterin is a sensitive indicator too: activated T cells produce interferon-y and macrophages secrete neopterin when exposed to endogenous or exogenous
interferon-y.
Our data on neopterin measurements in HIV-infected members of groups at risk for AIDS and in patients with prodromes or AIDS suggest that activation of cell-mediated immunity is a major factor in susceptibility to progressive HIV infection.2,3 Persistently activated T cells were found even in some seronegative individuals at risk of AIDS. Activated T cells were demonstrated in homosexuals practising receptive anal intercourse.4 Among drug abusers, only those adminstering drugs parenterally have activated T cells.’ Such activation was also observed in recipients of multiple blood transfusions.2 Thus
conditions associated with high susceptibility to infection are coupled with the presence of activated T cells .2Even when only a very small amount of HIV is inoculated, these conditions might predispose to measurable seroconversion since replication will start immediately after reverse transcription and insertion of the viral code into T cell DNA.
progressive HIV
Your editorial asks "Why are there such striking differences between Africa and the rest of the world in the mode of spread of HIV?" In an East African malaria study we found that a large proportion of apparently healthy Tanzanians had, surprisingly, activated T cells. On physical examination, most had evidence of infections by parasites or fungi.6 High activation of the cellmediated immune system was demonstrated for infection by Plasmodium falciparum or vi’vax6 and Mycobacterium tuberculosis,7 infections also occurring among inhabitants of Africa of either sex. The ensuing state of activation may increase susceptibility to HIV infection and progression to symptoms, irrespective of sex. The pattern of HIV seroconversion will then reflect that of other sexually transmitted diseases. Activation of the immune system as a co-factor in AIDS explains the epidemiological features of the infection and the close correlation between HIV infection and malarias or tuberculosis.9
This concept may help us to understand why newborn babies and pregnant women seem especially susceptible to rapid disease progression. In pregnancy neopterin concentrations are raised and in infants repeated activation of cell-mediated immunity occurs during primary contacts with various pathogens. Very high neopterin levels are found in infants during infectious episodes. A major part of your editorial deals with markers of disease progression. Neopterin levels specifically reflect activation of the cellular immune system and thus identify patients at special risk long before AIDS develops. Measurement of neopterin can be recommended to define the status of HIV infected individuals. The definition of risk groups is based on the mode of HIV transmission. Our data indicate that the most important fact that defines the risk of AIDS is a persistent state of T cell activation.
m
Institute of Medical Chemistry and Biochemistry and Institute of Hygiene, University of Innsbruck, and Ludwig Boltzmann Institute for AIDS Research, A-6020 Innsbruck, Austria 1. Huber C, Batchelor
H. WACHTER D. FUCHS A. HAUSEN G. REIBNEGGER E. R. WERNER M. P. DIERICH
JR, Fuchs D, et al. Immune response-associated production of neopterin—Release from macrophages primarily under control of interferongamma. J Exp Med 1984; 160: 310-16
SIR,-Patients with confirmed AIDS or AIDS-related complex have been found to have raised &bgr;2-microglobulin (&bgr;2-M) and neopterin levels.’ The screening of blood donors for HIV antibodies gave us an opportunity to study the early clinical and biological abnormalities in HIV infection. 97 anti-HIV
positive sera (enzyme immunoassay, confirmed by blot) were detected among 125 000 blood donors in Paris. Detailed examination, done within a month of antibody detection, revealed that 67 % were effectively clinically symptomless; 26 % had a lymphadenopathy syndrome and 7% had lesser forms of AIDS. 15 of the 65 symptomless donors had no abnormal laboratory findings such as anaemia and thrombocytopenia. Erythrocyte sedimentation rates were normal, IgG levels were above 16 g/1, and T4 and T8 counts were normal (T4 and T8 ratios above 1). western
and neopterin were measured by radioimmunoassay (Pharmacia and Behring Laboratories, respectively). Levels in anti-HIV positive donors were compared with those in 46 seronegative donors of similar age distribution. Both neopterin and (3Z M were significantly increased in anti-HIV positive donors, irrespective of clinical status and other laboratory findings (table). Even the 15 donors with neither symptoms nor laboratory test abnormalities had significantly increased levels of (32 M and neopterin. There was a correlation between &bgr;2 -M and neopterin (r =0 67); perhaps these increases reflect accelerated turnover of T cells.
P2-M
NEOPTERIN AND
B2-MICROGLOBULIN LEVELS IN ANTI-HIV
NEGATIVE AND POSITIVE BLOOD DONORS
LAD lymphadenopathy syndrome. Results as mean (SD). All means in anti-HIV-positive donors and subgroups significantly greater than means for serognegative donors (p < 0 001; Mann-Whitney rank test). =
Neopterin and &bgr;2-M seem to be early markers of infection by HIV, even in the absence of clinical and biological manifestations of HIV infection. These markers, though non-specific for HIV infection,5,6rise with the appearance of anti-HIV antibodies and before the
lymphocyte counts fall.
Centre National de Transfusion 75015 Pans, France
1. Francioli
Sanguine,
P. LAMBIN H. DESJOBERT M. DEBBIA J. M. FINE J. Y. MULLER
P, Clement F, Vaudois CHU. Beta2 microglobulin and immune-deficiency a homosexual man. N Engl J Med 1982; 307: 1402-03 2 Bhalla RB, Safai B, Pahwa S, Schwartz MK. Beta2 microglobulin as a prognostic marker for development of AIDS. Clin Chem 1985, 31: 1411-12. 3 Wachter H, Fuchs D, Hausen A, et al. Elevated unnary neopterin levels in patients with acquired immunodeficiency syndrome (AIDS) Z Physiol Chem 1983; 364: 1345-46. 4. Abita JP, Cost H, Milstein S, Kaufman S, Saimot G. Urinary neopterin and biopterin levels in patients with AIDS and AIDS related complex. Lancet 1985; ii: 51-52. 5. Cooper EH, Forbes MA, Hambling MH. Serum beta2 microglobulin and C reactive protein concentration in viral infections. J Clin Pathol 1984; 37: 1140-43. 6. Kem P, Rokos H, Dietrich M. Raised serum neopterin levels and imbalances of T lymphocytes subjects in viral diseases, acquired immune deficiency and related lymphadenopathy syndrome. Biomed Pharmacother 1984; 38: 407-11
WHO WILL GET AIDS? to
SIR,—Your Oct 25 editorial asks for factors that might contribute increased susceptibility to HIV infection and HIV-related
disease. In-vitro data show that activation of T cells is the basic event regulating HIV propagation and cell death. Thus measurement of T cell activation in AIDS patients and in risk groups should contribute to our understanding of the pathogenesis and epidemiology of AIDS. A sensitive and specific tool for detecting activation of the T cell/macrophage system is the measurement of neopterin in urine and serum.’ Neopterin is a sensitive indicator too: activated T cells produce interferon-y and macrophages secrete neopterin when exposed to endogenous or exogenous
interferon-y.
Our data on neopterin measurements in HIV-infected members of groups at risk for AIDS and in patients with prodromes or AIDS suggest that activation of cell-mediated immunity is a major factor in susceptibility to progressive HIV infection.2,3 Persistently activated T cells were found even in some seronegative individuals at risk of AIDS. Activated T cells were demonstrated in homosexuals practising receptive anal intercourse.4 Among drug abusers, only those adminstering drugs parenterally have activated T cells.’ Such activation was also observed in recipients of multiple blood transfusions.2 Thus
conditions associated with high susceptibility to infection are coupled with the presence of activated T cells .2Even when only a very small amount of HIV is inoculated, these conditions might predispose to measurable seroconversion since replication will start immediately after reverse transcription and insertion of the viral code into T cell DNA.
progressive HIV
Your editorial asks "Why are there such striking differences between Africa and the rest of the world in the mode of spread of HIV?" In an East African malaria study we found that a large proportion of apparently healthy Tanzanians had, surprisingly, activated T cells. On physical examination, most had evidence of infections by parasites or fungi.6 High activation of the cellmediated immune system was demonstrated for infection by Plasmodium falciparum or vi’vax6 and Mycobacterium tuberculosis,7 infections also occurring among inhabitants of Africa of either sex. The ensuing state of activation may increase susceptibility to HIV infection and progression to symptoms, irrespective of sex. The pattern of HIV seroconversion will then reflect that of other sexually transmitted diseases. Activation of the immune system as a co-factor in AIDS explains the epidemiological features of the infection and the close correlation between HIV infection and malarias or tuberculosis.9
This concept may help us to understand why newborn babies and pregnant women seem especially susceptible to rapid disease progression. In pregnancy neopterin concentrations are raised and in infants repeated activation of cell-mediated immunity occurs during primary contacts with various pathogens. Very high neopterin levels are found in infants during infectious episodes. A major part of your editorial deals with markers of disease progression. Neopterin levels specifically reflect activation of the cellular immune system and thus identify patients at special risk long before AIDS develops. Measurement of neopterin can be recommended to define the status of HIV infected individuals. The definition of risk groups is based on the mode of HIV transmission. Our data indicate that the most important fact that defines the risk of AIDS is a persistent state of T cell activation.
m
Institute of Medical Chemistry and Biochemistry and Institute of Hygiene, University of Innsbruck, and Ludwig Boltzmann Institute for AIDS Research, A-6020 Innsbruck, Austria 1. Huber C, Batchelor
H. WACHTER D. FUCHS A. HAUSEN G. REIBNEGGER E. R. WERNER M. P. DIERICH
JR, Fuchs D, et al. Immune response-associated production of neopterin—Release from macrophages primarily under control of interferongamma. J Exp Med 1984; 160: 310-16