Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum

Summary Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients. No serious side effects were recorded in any of the treated patients.Abbreviations AIDS acquired immunodeficiency syndrome - ALL/3 acute lymphoblastic leukaemia (FAB classification type 3) - AML/1 acute myeloblastic leukaemia (FAB classification type 1) - CDC center of disease control - CML/CP chronic myelocytic leukaemia (chronic phase) - CMV cytomegalovirus - CVID common variable immunodeficiency - DHPG 1,3-dihydroxy-2-propoxymethyl-guanine (gancyclovir) - ELISA enzyme-linked immunosorbent assay - GvHD graft versus host reaction - HIV human immunodeficiency virus - IgA immunoglobulin A - IgG immunoglobulin G - IgM immunoglobulin M - INH isoniazid - LIG Lactobin - MAI mycobacterium avium intracellulare - RAEB-T refractory anaemia with excess of blasts-transformation - SD standard deviation     

The detection of antithyroglobulin activity in human serum monoclonal immunoglobulins (monoclonal gammopathies)

The sera of 159 patients with monoclonal gammopathies were examined for the presence of anti-thyroglobulin (Tg) activity. An enzyme-linked immunosorbent assay was employed. Thirty-one (19.5%) sera were found to bind Tg. The activity against Tg was further confirmed by using purified immunoglobulins and employing competition assays. The anti-Tg antibodies were found in the sera of patients with IgG, IgM and IgA gammopathies. Anti-Tg antibodies were more frequent among patients with IgG gammopathy. Autoantibodies to Tg are found in patients with Hashimoto's thyroiditis, Graves' disease and occasionally in patients with thyroid carcinoma. Natural autoantibodies directed against human Tg have been detected, as well, in healthy subjects. None of the patients in the present study whose serum was found to contain high titers of anti-Tg human monoclonal antibodies had any clinical or biochemical evidence of thyroid disease. Our results of a high incidence of anti-Tg activity in the sera of patients with monoclonal gammopathies support previous reports of autoantibody properties characteristic of these immunoglobulins.     

Lymphocyte subpopulation reference ranges for monitoring human immunodeficiency virus-infected Chinese adults.

Two hundred eight healthy human immunodeficiency virus (HIV) type 1- and HIV type 2-seronegative Chinese adults (78 males and 130 females; mean age, 32 years; age range, 18 to 71 years) were analyzed for lymphocyte subsets by a standardized and quality-controlled flow cytometric immunophenotyping technique. While the leukocyte differential values were comparable to those found in studies of Caucasians, the means, medians, and 95% reference ranges of lymphocyte subsets were very different. The 95% reference ranges in absolute counts per microliter of whole blood (percentage of lymphocytes) for CD3+, CD3+ CD4+, CD3+ CD8+, CD3- CD19+ (B), and CD3- with CD16+ and/or CD56+ (NK) cells were 672 to 2,368 (54.8 to 83.0%), 292 to 1,366 (23.1 to 51.0%), 240 to 1,028 (17.9 to 47.5%), 82 to 560 (5.1 to 20.8%), and 130 to 938 (7.1 to 38.0%), respectively. CD3+ CD4+ cells showed significant sex difference (for males, mean of 702 [34.8%] and standard deviation of 258 [7.5%]; for females, mean of 728 [37.3%] and standard deviation of 254 [7.4%]) as well as an increase with age of 42 (1.6%) per decade. Investigations of the NK cell population did not show similar findings. Classification of HIV disease, treatment, and prophylactic regimens based on studies which relied heavily on estimations of lymphocyte subsets alone should be used with special caution for Chinese patients. Provided that adequate quality control measures are taken to ensure comparability of data, we recommend that these ranges be used on a day-to-day basis in laboratories that have not yet established their own reference ranges.     

Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)-infected patients

Infection by the human immunodeficiency virus is associated with polyclonal B cell activation and increased levels of serum IgA. In order to characterize the molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in sera from 60 HIV-1-infected patients and 40 healthy controls. In addition, secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory component (SC), and the distribution of monomeric and polymeric IgA were determined. The data confirm the elevation of total serum IgA levels in HIV-1-infected patients, and both IgA1 and IgA2 concentrations are elevated. Furthermore, the data show a substantial increase in serum levels of both monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in CDC group II patients versus controls and more frequently elevated in CDC group IV patients. The highest S-IgA levels were found among patients with the lowest blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in HIV-1-infected patients and positively correlated with serum S-IgA levels. Conversely, serum levels of free SC were not altered. An increase in serum S-IgA was not related to human hepatitis B virus infection and/or to hepatic dysfunction or to diarrhea or overt intestinal infection. The data indicate that secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites, increase in the serum of HIV-1-infected patients.     

BK virus infection in human immunodeficiency virus-infected patients

The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV-infected patients; however, no role for BKV has been demonstrated in this population.     

Specificity of the antibody response to the pneumococcal polysaccharide and conjugate vaccines in human immunodeficiency virus-infected adults

Nonspecific antibodies, which are thought to be nonprotective, have been shown to contribute a substantial proportion of the measured concentration in the standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for pneumococcal polysaccharide capsular antibodies. The presence of such antibodies in human immunodeficiency virus (HIV)-infected persons has not been evaluated. The amount of nonspecific antibodies is proportional to the reduction in IgG antibody concentration that occurs with serum absorption with the heterologous polysaccharide 22F. We measured the amount of nonspecific antibodies before and after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4 counts of >/== 200 cells/mm3. Blood was drawn before and 2 months after vaccination. For prevaccination sera, we found a substantial amount of nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured IgG concentration), but not for serotype 14. There tended to be proportionately less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but not for PPV. Subjects with a low HIV viral load (相似文献   

Cross-sectional study of nasopharyngeal carriage of Streptococcus pneumoniae in human immunodeficiency virus-infected adults in the conjugate vaccine era

Human immunodeficiency virus (HIV)-infected patients have an increased rate of pneumococcal infections. Within the HIV-infected population, patients with low CD4⁺ cell counts have a higher rate of pneumococcal infection. The purpose of our study was to determine pneumococcal carriage and to examine the serotypes carried by HIV-infected patients after the introduction of the conjugate vaccine. Nasopharyngeal swabs were obtained from patients during routine clinic visits. Samples were cultured on blood agar plates with gentamicin and screened for alpha-hemolysis, optochin sensitivity, and bile solubility. Capsular serotypes were determined by multiplex PCR, multibead assay, or latex agglutination. Antibiotic susceptibility was determined by the Etest method. Multilocus sequence typing was also performed. Of the 175 patients enrolled, 120 patients had absolute CD4⁺ cell counts above 200/mm³ and 55 had counts below 200/mm³. A total of six (3.4%) patients carried pneumococci. All but one of these patients had received the 23-valent pneumococcal vaccine within the previous 5 years. Five of the isolates were serotypes that are not included in the 7-valent conjugate vaccine. Immunization with the pneumococcal polysaccharide vaccine does not prevent colonization in HIV-infected patients; however, the observation of carriage of serotypes not included in the conjugate vaccine may be due to herd immunity and serotype replacement effects in the general population.     

Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects

Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.     

Accessory cell function in asymptomatic human immunodeficiency virus-infected patients

Peripheral blood mononuclear cells from human immunodeficiency virus seropositive (HIV+) individuals who did not exhibit symptoms of acquired immunodeficiency syndrome (AIDS) (Walter Reed Stage 1 patients) were tested for accessory cell function for presentation of recall antigens to autologous T lymphocytes and for presentation of HLA alloantigens to T lymphocytes from healthy, HIV- donors. Neither experimental model indicated a defect in accessory cell function at this early stage after HIV infection, although our study does not exclude the possibility of accessory cell dysfunction at a later stage of AIDS development.     

Fulminant human herpesvirus six encephalitis in a human immunodeficiency virus-infected infant

Self-limited involvement of the central nervous system (CNS) is a relatively common complication of primary infection with human herpesvirus six (HHV-6) in normal children. We describe an HIV-infected infant who developed fulminant encephalitis as a complication of HHV-6 infection. Immunohistochemical staining of CNS tissue demonstrated productive infection of all CNS cell-types. Analysis of the infected brain tissue by the polymerase chain reaction (PCR) confirmed the presence of a dense HHV-6 infection in the tissue, and demonstrated that the virus present in the CNS tissue was predominantly the A variant of HHV-6. This is the first demonstration of invasive tissue disease caused by HHV-6 in an HIV-infected infant. © 1995 Wiley-Liss, Inc.     

Affinity immunoblotting detection of serum monoclonal immunoglobulins reactive with glycosphingolipids

The characterization of serum monoclonal IgM reactive with glycosphingolipid present in the nervous system is of major importance in patients with certain neuropathies. A rapid, sensitive and specific one-step method which permits such a characterization is described. Serum immunoglobulins separated by high resolution agarose electrophoresis are transferred to affinity filters (nitrocellulose sheets coated with glycolipids), and revealed with enzyme-tagged monospecific anti-immunoglobulin antibodies.     

Production and characterization of high-affinity human monoclonal antibodies to human immunodeficiency virus type 1 envelope glycoproteins in a mouse model expressing human immunoglobulins

Human (Hu) monoclonal antibodies (MAbs) against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) are useful tools in the structural and functional analysis of Env, are under development both as potential prophylaxis and as therapy for established HIV-1 infection, and have crucial roles in guiding the design of preventative vaccines. Despite representing more than 50% of infections globally, no MAbs have been generated in any species against C clade HIV-1 Env. To generate HuMAbs to a novel Chinese C clade Env vaccine candidate (primary isolate strain HIV-1(97CN54)), we used BAB5 mice that express a human immunoglobulin (Ig) M antibody repertoire in place of endogenous murine immunoglobulins. When immunized with HIV-1(97CN54) Env, these mice developed antigen-specific IgM antibodies. Hybridoma fusions using splenocytes from these mice enabled the isolation of two Env-specific IgM HuMAbs: N3C5 and N03B11. N3C5 bound to HIV-1 Env from clades A and C, whereas N03B11 bound two geographically distant clade C isolates but not Env from other clades. These HuMAbs bind conformational epitopes within the immunodominant region of the gp41 ectodomain. N3C5 weakly neutralized the autologous isolate in the absence of complement and weakly enhanced infection in the presence of complement. N03B11 has no effect on infectivity in either the presence or the absence of complement. These novel HuMAbs are useful reagents for the study of HIV-1 Env relevant to the global pandemic, and mice producing human immunoglobulin present a tool for the production of such antibodies.     

Elimination of false-positive serum reactivity in latex agglutination test for cryptococcal antigen in human immunodeficiency virus-infected population.

We recently tested serum from a human immunodeficiency virus-infected patient for the presence of cryptococcal antigen using the Meridian latex agglutination (LA) test (Cryptococcal Antigen Latex Agglutination System). Two pronase-treated serum specimens from the patient had LA titers of 80 and 160, but the patient had no evidence of cryptococcal disease. The serum was negative for rheumatoid factor, a well-documented cause of false-positive LA reactions. Seven blood culture supernatants from the patient were also LA positive, but were culture negative for cryptococcus. When the sera and blood culture supernatants were treated with 0.01 M 2-beta-mercaptoethanol (2-ME), the agglutinating activity was ablated. Similar results were seen when the sera were tested by two other commercial LA assays. Serum and cerebrospinal fluid specimens from patients with confirmed cryptococcal disease were treated with 2-ME, and the results were compared with those obtained after pronase (sera) or heat (cerebrospinal fluid) inactivation. The titers were identical (n = 56) or within 1 dilution (n = 3). One hundred serum specimens from human immunodeficiency virus-seropositive patients with no known history of cryptococcal disease were examined to determine the frequency of false-positive reactivity in this patient population. Of this group, three were positive following pronase treatment. One remained positive after 2-ME treatment; the remaining two were negative. These data indicate that 2-ME can be used to eliminate nonspecific reactivity in the LA test without affecting true-positive results.     

Decreased serum lipocalin-2 levels in human immunodeficiency virus-infected patients: increase during highly active anti-retroviral therapy

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.     

Characterization of penicillin intermediate serotypes of Streptococcus pneumoniae carried by human immunodeficiency virus-infected adults and healthy children in Uganda

There are little data on the genetic relatedness between antibiotic-resistant pneumococcal isolates colonizing the Ugandan population. Penicillin-intermediate pneumococci of serogroups or serotypes rarely or not previously reported as being penicillin nonsusceptible were selected out of 166 isolates representing 26 capsular serogroups or serotypes isolated from Ugandan children in 1995 and human immunodeficiency virus (HIV) infected Ugandan adults in 2004-2005. Pairs of penicillin-intermediate pneumococci of the same serogroup or serotype present in both patient populations were characterized further by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Seven such pairs of isolates were found and included serogroups 7, 11, 15B/C, and 16 as well as serotypes 13, 21, and 35B. PFGE of these seven pairs showed no clonality between serogroups or serotypes, and clonality only within serogroup 11 and serotype 13. MLST of the 14 individual isolates revealed 13 different sequence types (STs), 11 of which had not previously been recorded. Comparisons with all known STs revealed that most of these strains were related only to strains of the same serotype in other countries, with these related strains frequently also being penicillin intermediate. These findings suggest that penicillin nonsusceptibility in Uganda is likely due to the introduction of antibiotic-resistant pneumococcal clones into Uganda rather than development of resistance within the country.     

Lower cognitive reserve in the aging human immunodeficiency virus-infected brain

More HIV-infected individuals are living longer; however, how their brain function is affected by aging is not well understood. One hundred twenty-two men (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed neuropsychological tests and had acceptable functional magnetic resonance imaging scans at 3 Tesla during tasks with increasing attentional load. With older age, SN and HIV+NC subjects showed increased activation in the left posterior (reserve, “bottom-up”) attention network for low attentional-load tasks, and further increased activation in the left posterior and anterior (“top-down”) attention network on intermediate (HIV+NC only) and high attentional-load tasks. HAND subjects had only age-dependent decreases in activation. Age-dependent changes in brain activation differed between the 3 groups, primarily in the left frontal regions (despite similar brain atrophy). HIV and aging act synergistically or interactively to exacerbate brain activation abnormalities in different brain regions, suggestive of a neuroadaptive mechanism in the attention network to compensate for declined neural efficiency. While the SN and HIV+NC subjects compensated for their declining attention with age by using reserve and “top-down” attentional networks, older HAND subjects were unable to compensate which resulted in cognitive decline.     

Disseminated Mycobacterium lentiflavum infection in a human immunodeficiency virus-infected patient

We report the first case of Mycobacterium lentiflavum disseminated infection in a human immunodeficiency virus-infected patient. Conventional identification procedures failed to identify the mycobacterial strain, but sequencing of the 16S rRNA gene led to the species identification. Furthermore, we describe here the analysis of the 16S-23S rRNA internal transcribed spacer sequence of M. lentiflavum.