Hyperimmune globulin therapy of clinical CMV disease in renal allograft recipients.
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Biomedical subjects
Publications and source records attributed to J Suni.
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An enzyme immunoassay (EIA) for serum antibodies to human immunodeficiency virus type 1 (HIV-1), based on the synthetic pentadecapeptide SGKLICT-TAVPWNAS, a segment of the transmembrane glycoprotein (gp41) of the virus, was developed and tested for sensitivity and specificity. Sera of 152 individuals at various stages of HIV-1 infection, including two prospectively and six retrospectively studied patients exposed to HIV-1 but seronegative on initial testing in whole-virus EIA and immunoblotting, were screened with the gp41 peptide antibody EIA. The reference population consisted of 1,000 healthy HIV-1 antibody-negative blood donors. In addition, five individuals with antibodies to HIV-2 were studied. Antibodies to the synthetic peptide were detected in 100% of those with asymptomatic infection. Only one patient with LAS failed to react in the peptide EIA. Patients with HIV-2 infection did not react in this test. The peptide antibodies appeared rapidly after infection, were detectable at the time when seroconversion was observed by immunoblotting, and preceded reactivity in whole-virus EIA. Sera of seven patients with verified HIV-1 infection did not react with gp41 in immunoblotting, although antibodies were readily detectable in the gp41 peptide EIA.
Since the human immunodeficiency virus (HIV) may be transmitted accidentally to laboratory personnel analyzing patient sera, the efficiency of a non-ionic detergent, Triton X-100, in inactivation of HIV in human serum as a safety measure was studied. Semliki Forest virus, an enveloped toga virus, was used as a model virus to create optimal treatment conditions. In the presence of 50% serum, complete inactivation (i.e. no residual virus detected, greater than 7 log reduction of virus titre) was achieved by incubation with 0.2% Triton X-100 for 1 h at 37 degrees C. Under these conditions HIV was also completely inactivated (i.e. no residual infectious virus detected, greater than or equal to 5 log reduction of virus titre). Both treated and untreated serum specimens were also tested with several enzyme immunoassays used in virological laboratories to determine whether the inactivation treatment interfered with the assays. The treated specimens, further diluted as recommended for each assay, were subjected to 15 enzyme immunoassays for microbial antibodies and antigens (HIV IgG, hepatitis A IgG and IgM, hepatitis B s, c, and e antigens and antibodies, cytomegalovirus IgG, mumps virus IgG, poliovirus IgG, rubellavirus IgM, toxoplasma IgG, and chlamydia IgG). Clearly decreased sensitivity was found only with two hepatitis B tests (e antigen and antibody to the surface antigen). It is concluded that safe inactivation of HIV in serum is achieved by 0.2% Triton X-100, but the treatment may decrease the sensitivity of some tests in which low specimen dilution is used.
The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.
The ECP Working Group on AIDS has evaluated the available data on seropositivity to HIV-1 supplied by research groups in 12 Eastern and Western European countries. The period covered is 1985 and 1986. A significantly elevated incidence of seropositives was observed in both females and males in heterosexual contact with members of high risk groups. In contrast heterosexuals with no such contact had an incidence below 1%. For male homosexuals from Italy, Denmark and Switzerland the trend was no detectable increase in prevalence from 1985 to 1986. Hungary and Poland now have a few per cent seropositive male homosexuals, but no seropositives were found in a group of Polish drug abusers.
A synthetic pentadecapeptide (A15; env residues 599-613: SGKLICTTAVPWNAS), derived from a hydrophobic region in the transmembrane protein gp41 of HIV-1 and comprising a highly immunoreactive antigenic site in eliciting antibody responses during HIV-1 infection in humans, was used to purify, by affinity, the corresponding anti-peptide antibodies from HIV-1-infected patient sera. The purified antibodies to peptide A15 reacted specifically with the peptide in EIA, but not in whole virus EIA. These antibodies were immunoreactive with the corresponding peptide-albumin conjugates in immunoblotting but not with gp41 molecules. The results suggest that the peptide A15 sequence is not exposed in intact gp41, but will be exposed and is antigenic in the course of HIV-1 infection in humans.
We analyzed the intrathecal humoral immunologic response in 42 human immunodeficiency virus (HIV)-infected patients. Eighteen patients had clinical neurologic abnormalities, while the remaining 24 patients were neurologically symptom-free. Nine of the neurologically symptomatic patients at early infection had slight neurologic dysfunction; in nine other subjects at late infection, the neurologic impairment was moderate or severe. When compared with symptom-free patients, neurologically symptomatic patients had increased intra-blood-brain barrier (BBB) HIV-specific IgG (p less than 0.001) and total IgG synthesis (p less than 0.01) with oligoclonal bands (OCBs) in the CSF and/or serum (11/18 versus 3/24). At early stages of the infection, neurologically symptomatic patients showed increased total intrathecal IgG synthesis (9/9) coincident with OCBs in the CSF and serum (7/9) and slight mononuclear pleocytosis (7/9), but less frequent HIV-specific IgG production within the CNS (6/9). In advanced infection, the number of neurologically symptomatic patients with intrathecal HIV-specific IgG synthesis (8/9) was higher, while the number of those with increased total intra-BBB IgG synthesis (5/9; p less than 0.01), OCBs (4/9), and increased CSF leukocyte count (1/9; p less than 0.001) was lower than at early infection. Our data suggest humoral intra-BBB immunoactivation at early stages of HIV infection followed by declining B cell response within the CNS at advanced infection.
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CSF protein and cellular profiles were studied in 28 HIV-infected patients. Twenty of them had neurological complaints, but only 6 patients had objective neurological deficits such as dementia, ocular motility disorders or polyneuropathy. The serum/CSF HIV antibody ratio was on average lowest in acquired immunodeficiency syndrome (AIDS) (4 patients) and highest or almost normal in lymphadenopathy syndrome (LAS) (11) and asymptomatic seropositivity (ASX) (7), while it varied between these extremes in AIDS-related complex (ARC) (6). However, low values of the ratio were also found in the HIV-infected patients free of neurological symptoms and even in one ASX patient. The CSF IgG index was elevated in all these 4 general stages of HIV infection without any significant differences between them. The CSF/serum albumin ratio was slightly increased in patients with neurological deficits, but this ratio showed no association with any other clinical factor analysed. CSF leucocytes were increased in the early stages of the disease, but later the cellular reaction subsided. HIV was isolated from post mortem brain tissue of two AIDS patients and from the CSF of one of them. The results suggest increased intrathecal virus-specific IgG synthesis, not only in patients with neurological deficits and at advanced stages of infection, but also in neurologically symptom-free subjects and at early infection. The lack of correlation between the increased virus-specific IgG synthesis within the CNS and the presence of neurological symptoms suggests that neurologically "silent" areas of brain white matter are often affected in HIV infection.
During a three-year follow-up study of 235 risk-group people living in Finland, we found a slow increase in the proportion of HIV seropositives (from 9.8% to 14.0%) and a slow but continuous advance in symptoms typical of HIV infection among them. The first immunological changes after HIV seroconversion were an increase in Ts-cells and a decline in antigen-induced T-cell functions (proliferation, IL-2 production). A further decline in antigen-induced responses was seen before early clinical symptoms and signs of HIV infection developed. During later phases of HIV infection the decrease of Th-cells and the elevation of serum Beta-2 microglobulin correlated most strongly with the progression of HIV infection. The mitogen-induced lymphocyte functions of the HIV-infected correlated to Th-cell levels, while the antigen-induced proliferation and IL-2 production showed correlation neither to Th-cells nor to Ts-cells. The poor antigen-induced T-cell responses might be caused by abnormally functioning monocytes, known to be infected by HIV. Our results suggest that in HIV infection there is a continuous but slow disease progression, although individual variation may be great. The immunological parameter best predicting the prognosis of an infected person in the early phases of infection was the antigen-induced lymphocyte functions, and later the amount of Th-cells.
The presence of HIV (human immunodeficiency virus) particles in the tear fluid, on the conjunctival surface or in the contact lenses of patients with chronic HIV infection has made it necessary to establish better for guide-lines for decontamination of instruments during ophthalmological procedures. The methods are now at the stage of evolution. The present paper describes the disinfection procedures used in the Helsinki University Eye Hospital and updates the present decontamination protocols.
A 47-year-old female with acute myeloid leukemia received HIV positive platelets during induction chemotherapy. 18 days later, coincident with the recovery of the bone marrow function, she developed an erythematous rash, mild lymphadenopathy, and nausea which disappeared within 10 days. A week later mild CSF pleocytosis consisting of mature lymphocytes and macrophages together with elevated CSF protein levels (1,080 mg/l) were observed suggesting mild aseptic meningitis, and the HIV was concomitantly isolated from CSF. The CSF abnormalities have improved and the patient is well and in remission after 3 cycles of chemotherapy. This case expands the clinical spectrum of HIV infection to include a primary syndrome during immunosuppression from an unrelated cause.
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