Assessment of interleukin-1 beta mRNA expression in the norm and pathology]

We investigated cytoplasmic RNA from the peripheral blood cells of pollinosis patients. Increased levels of IL-I mRNA were registered in neutrophils of patients suffering from pollinosis for a long time. Neutrophils from patients at the time of exacerbation of pollinosis responded to stimuli less than the cells from healthy donors. During remission the activated neutrophils from pollinosis patients and those from healthy donors had same levels of IL-I mRNA.     

Effect of anti-herpes specific transfer factor

Using a blood cell separator, lymphocytes were collected from otherwise healthy convalescents suffering from herpetic infections. A specific anti-herpes dialysate (AH-DLE) was prepared from the lymphocytes, using standard procedures. Patients with recurrent herpetic infections were treated with a single dose of the dialysate, at the initial signs of herpetic infection (group A), with two doses (group B) or with three doses (group C). A total number of 37 patients (29 women, 8 men, age range 15–73 years) were treated. No improvement was observed in 7 patients (18.9%), whilst 7 patients did not manifest any exacerbation of their herpetic infection in the course of the one-year follow-up. The remaining 62.2% of the patients showed a marked improvement: decrease of the frequency and/or duration or relapses. Before AH-DLE administration, the mean number of herpes relapses in this group of patients was 12 p.a.. After therapy, the number of relapses decreased to 3.5 p.a.. No statistically significant difference was observed between groups A and B. The least favourable results were registered in group C. However, this group included 6 female patients extremely resistant to the previously therapeutic attempts, including inosiplex, non-specific DLE or acyclovir. Thus, even in this group, the therapy was successful in 50% of the patients.     

Assessment of the functional activity of lymphokine-activated killer cells in healthy donors and in patients with interleukin-2-dependent immunodeficiency

The methodological aspects of Lak-cells functional activity test were determined. NK-resistance of P-815 culture cells and NK-sensitive K-562 cells were used as target cells. The highest cytotoxicity level was registered at the 5-th day of culturing MNC with rIL-2 at the final concentration (100 U/ml). The method developed was used for testing healthy donors group and group of patients with IL-2 dependent immunodeficiency (ophthalmic herpes). Data obtained show the significant decrease of LAK-cells functional activity of patients in comparison with healthy donors. Thus, the developed method is recommended for complex estimation of immune status of patients with IL-2-dependent immuno deficiency.     

Immunological indices of patients with ragweed pollinosis

A comparative study of local and humoral immunity in patients with increased sensitivity to ragweed pollen and in healthy persons has been carried out. In untreated patients a six-fold increase of the levels of total IgE and specific anti-ragweed IgE-antibodies in the blood sera and secretions has been registered, which corresponds to the 3rd and 4th grade reaction in the enzyme immunoassay; simultaneously, a decrease in the characteristics of immune responsiveness has been observed. As the levels of total IgE and specific IgE-antibodies are of particular diagnostic value in immediate-type allergic diseases, the authors have examined the patients with ragweed pollenosis at the periods of the absence of clinical manifestations and in the exacerbation of the disease during blossoming with pollen formation. During exacerbation the level of immunoglobulins of all classes, specific IgE-antibodies in the blood sera and secretions of patients, as well as some characteristics of immune responsiveness, are higher than in remission, which is indicative of the increased antigenic stimulation of the body and of the developing immune response.     

ELISA间接法检测呼吸道合胞病毒和副流感病毒血清IgM和IgA抗体

建立了检测呼吸道合胞病毒(RSV)和副流感病毒(PFV)血清特异性IgM和IgA抗体的间接ELISA方法。在方法统一的基础上比较了检测IgG、IgM和IgA抗体的结果,证明检测血清IgM和IgA可以作为RSV和PFV感染的早期诊断指标。检测了120份临床急性下呼吸道感染患儿的血清,RSV-IgM检出率为33.3％,RSV-IgA为36.7％;PFV-IgM为27.5％,PFV-IgA为31.6％。提出了对RSV和PFV感染以检测特异性IgA替代IgM或两者互补的设想。     

Diagnostic value of dengue virus-specific IgA and IgM serum antibody detection

The diagnostic value of dengue virus (DV)-specific immunoglobulin A (IgA) serum antibody detection, by an indirect immunofluorescence assay (IFA) was evaluated. For this study, the kinetics of DV-specific IgA serum antibodies was analysed in two experimentally immunised macaques, paired samples from 35 patients suspected of a primary or secondary DV infection, paired sera from patients with high levels of IgA specific antibodies against influenza virus (n = 15), sera from patients with other viral infections (n = 40) and healthy blood donors (n = 10), which served as controls. The presence of DV-specific IgA serum antibodies in humans and in monkeys was compared with that of DV-specific IgM demonstrated in a capture enzyme-linked immunosorbent assay (ELISA). The development of DV-specific IgA and IgM antibodies in macaques proved to be similar to that observed in humans with a DV infection. In sera obtained from suspected primary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 1/6 (17%) and 6/6 (100%), whereas IgM was detected in 4/6 (67%) and 5/6 (83%), respectively. In sera from suspected secondary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 18/29 (62%) and 28/29 (97%), whereas IgM was detected in 20/29 (69%) and 28/29 (97%), respectively. The control group consisted of five paired serum samples from yellow fever vaccinated individuals and a patient with acute tick-borne encephalitis, 15 paired serum samples from patients with high levels of IgA antibodies specific for influenza virus and 40 serum samples from patients with specific IgM antibodies against other viruses. Ten serum samples from healthy blood donors were included. Among the control serum samples, in one patient, both DV-specific IgA and IgM antibodies were present, and in three sera DV-specific IgM antibodies could be demonstrated. These data suggest that detection of DV-specific IgA serum antibodies by IFA may have additional value for the diagnosis of DV infection.     

Humoral response to selected antigens of Yersinia enterocolitica and Yersinia pseudotuberculosis in the course of yersiniosis in humans. I. Occurrence of antibodies to Yersinia lipopolisacharydes and Yop proteins by ELISA

The antibodies against the somatic antigens of Y. enterocolitica O3, O8, O9, O5,27,Y. pseudotuberculosis I, and released proteins Yop were detected using the ELISA in 1634 serum samples and 84 synovial fluids collected from 1290 persons suspected for yersiniosis, as well as 200 serum samples from healthy individuals (blood donors). The presence of antibody in diagnostically significant titres for somatic antigens of Yersinia were detected by ELISA in 20.5% and 50.6%, antibodies for released proteins Yop in 11.5% and 28.4% respectively of blood donors and patients suspected for yersiniosis. The antibody against the O3 antigen of Y. enterocolitica was the most frequently detected antibody while the most infrequent was the antibody for the antigen from the 08 serologic group. The results of the study showed that the humoral response picture to Yersinia antigens in the course of yersiniosis in humans is dependent on the age and sex of the patient, duration of the infection, and clinical manifestations. Most frequently the elevated antibody levels were detected among patients with erythema nodosum and patients with gastrointestinal symptoms. The frequency of occurrence of antibodies for most antigens of Yersinia, together with age increased reaching its peak, on the average, among individuals aged 21 - 40 years. Analysis of individual cases showed that by the end of the first week of infection, elevated levels of antibodies for somatic antigens of Yersinia are evident. On the other hand, antibodies for released proteins Yop as a matter of rule appear in the second week from the onset of clinical symptoms. Within this early phase of infection immunoglobulins of the A and M classes dominate reaching their highest level in the second to third week of the infection. In majority of the individuals studied antibodies of the IgG class reached their highest level much later in relation to those of the IgA and IgM classes. Significant differences were found in IgA antibody detection among individuals with clinical manifestations of stomachaches and arthritis. Nevertheless, among individuals with clinical symptoms of stomachaches, these immunoglobulins as a matter of principle disappear with a period of 2-3 months from the onset of clinical symptoms. In individuals with arthritis however the aforementioned immunoglobulins maintained at considerable levels even after a year. In joint-fluid samples obtained from patients with arthritis antibodies for Yersinia antigens were detected in similar levels just as obtained simultaneously serum from those individuals.     

Serum immunoglobulin levels in various forms of meningococcal infection and in meningococcus carriers

The levels of serum IgG, IgA and IgM were examined in 191 adults including 103 patients with various forms of meningococcal infection, 32 meningitis convalescents and 56 carriers, in order to elucidate the causes of different susceptibility to the meningococcal infection. The IgD level was determined in 54 meningitis patients as well as in convalescents and carriers. The amount of immunoglobulins was determined by radial immunodiffusion. The level of IgG at the beginning of the disease in patients with the generalized forms of meningococcal infection (meningitis, meningitis combined with meningococcaemia, meningococcaemia) was found to be considerably lower than in healthy subjects. The levels of all immunoglobulins, particularly of IgA and IgM, increased in the course of the disease. The levels of IgG, IgA and IgM in meningitis convalescents a year after recovery were found to be the same as in the controls. The levels of IgG, IgA and IgM in patients with meningococcal nasopharyngitis were significantly lower than in healthy subjects. The carriers showed a decreasd level of IgA and a considerably increased level of IgG while the levels of IgM and IgD did not differ from the control.     

Secondary diseases in HIV-infected patients

During the period of 1980-1996 the dispensary observation of 50 HIV-infected patients was carried out. The clinical forms of the infection were distributed among these patients as follows: asymptomatic forms in 18 patients, persisting generalized lymphadenopathy in 8 patients, pre-AIDS in 14 patients, AIDS in 10 patients. Secondary infections were registered at the pre-AIDS stage. Dermatoses, oropharyngeal candidiasis occurred most frequently: in 52% of the HIV-infected patients. Herpes virus infection was registered in 46% of the patients. At the stage of AIDS during the generalized herpes virus and cytomegalovirus infections were registered in 5 and 7 patients respectively. Generalized forms of combined infections (herpes virus + fungi) prevailed, which caused the death of 7 patients at the terminal stage of AIDS.     

Intensity of the production of rheumatoid factor in patients with different degree of sensitization to Borrelia garinii antigens

The content of rheumatoid factor and serum IgA, IgM and IgG in patients with different degree of sensitization to B. garinii antigens is evaluated. An increase in the titer of rheumatoid factor in patients with a high content of antibodies to Borrelia was established. In addition, an increased concentration of serum immunoglobulins in the presence of Borrelia infection was registered. The mechanisms of autoimmune reactions are discussed, proceeding from the biological properties of the causative agent of Lyme disease.     

Dynamics of the accumulation of the basic immunoglobulin classes in the intestinal contents in food toxinfections]

The work presents the data on the dynamics of accululation of the main classes of immunoglobulins (A, G and M) in coprofiltrates obtained from patients with alimentary toxicoinfections (bacteriologically confirmed salmonellosis and diseases of unknown etiology). The levels of immunoglobulins of all classes (mainly IgA and IgG) were shown to be elevated in the process of the disease. The dynamics of the increase in the level of IgA (both general and secretory) was supposed to indicate the formation of local immunity in the intestinal wall. The presence of serum IgA and the characteristic IgG dynamics seemed to be indicative of destructive processes occurring in the intestinal wall. Thus, the dynamics of accumulation of immunoglobulins in coprofiltrates obtained from patients with alimentary toxicoinfections reflects the main local pathological and immunological processes.     

Experimental trichinosis-II. Quantitative and qualitative variations of serum in CBA mouse and Wistar rat (author's transl)]

Variations of serum globuline and immunoglobulins were measured by electrophoresis on cellulose acétate and radial immunodiffusion during the course of infection in inbred CBA mice and Wistar rats.In the two animal species, electrophoresis showed a significant decrease of serum albumin attending an increase of γ globulins. This phenomenon was earlier and greater in mice than in rats. This difference might be explained by suggesting that Trichinella is better adapted to rats than to mice.Beginning in the second week of infection, all classes of immunoglobulins were increased in the mouse with IgG_2a and IgA showing the greatest increase. The different classes of immunoglobulins continued to increase during the 4th month of infection but the rate of increase diminished after the second month except for IgA which increased between the 60th and 120th day.     

Immunoglobulin G is the main protective antibody in mouse vaginal secretions after vaginal immunization with attenuated herpes simplex virus type 2.

We investigated the protective role of antibodies in vaginal secretions of mice that were immune to vaginal challenge with herpes simplex virus type 2 (HSV-2). Unfractionated vaginal immunoglobulins from immune and nonimmune mice and affinity-purified immunoglobulin G (IgG) and secretory IgA (S-IgA) from immune secretions were adjusted to their concentrations in vivo. Wild-type HSV-2 was incubated in the immunoglobulin preparations for 15 min in vitro, followed by inoculation into vaginae of nonimmune mice. HSV-2 was neutralized by unfractionated antibody and purified IgG from immune secretions but not by unfractionated nonimmune antibody or by purified immune S-IgA. The protective effect of IgG in vivo was investigated by passively transferring purified serum IgG from immune and nonimmune donors to nonimmune recipients before vaginal challenge infection. Immune IgG significantly reduced the percentage of vaginal epithelium infected, concentrations of shed virus protein in the vaginal lumen, and illness scores, even though the viral antibody titers in serum and vaginal secretions of recipient mice at the time of challenge were only 29 and 8%, respectively, of those in actively immunized mice. Additionally, removal of vaginal secretions from immune mice 10 min before vaginal challenge with HSV-2 significantly increased the concentration of shed virus protein in the vaginal lumen after challenge. Collectively, the data indicate that IgG antibody in vaginal secretions of immune mice provides early protection against vaginal challenge infection, probably by neutralizing virus in the vaginal lumen. In contrast, S-IgA antibody contributed relatively little to immune protection of the vagina.     

Prevention of infection transmission during stem cell transplantation

Group of 152 patients (investigated before autologous transplantation) and 35 healthy donors for allogeneic transplantation was examined for the risk of infection transmission that can be associated with the infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross-contamination of stored grafts. No laboratory signs of active infection were found in 22 donors (63 %) and in 91 patients (60%). The most common was active infection by herpes viruses--50 cases in patients, 21 cases in donors; hepatitis B was found in only two cases. The rate of clinically unsuspected (but dangerous) infections in donors and patients thus remains relatively high in spite of the fact that the system of donor search and the whole transplantation procedure have improved in the last years. The system of safety assurance is extremely important and the whole palette of preventive tests according to EBMT (European Blood and Marrow Transplantation Group) and ISHAGE (International Society for Hemotherapy and Graft Engineering) is fully justified.     

Characterization of anti-Cryptosporidium IgA antibodies in sera from immunocompetent individuals and HIV-infected patients.

Human antibody response to Cryptosporidium parvum has been previously shown as involving immunoglobulin (Ig)M and IgG isotypes. The interest in anti-cryptosporidial IgA antibody response has been recently stimulated by studies on the therapeutic effects of secretory IgA antibodies to Cryptosporidium in animal models and in patients. In the present study, isotypes of serum anti-Cryptosporidium antibodies have been characterized in donors of the following categories: (a) healthy adults, (b) healthy children, (c) immunocompetent children with transient cryptosporidial diarrhea, (d) HIV-infected patients without clinical and parasitological evidence of Cryptosporidium infection and (e) AIDS patients with cryptosporidial diarrhea. Antibodies were detected using C. parvum oocysts purified by density gradient centrifugation from bovine faeces. The IgA antibodies were revealed using alpha-chain specific antibodies. Indirect immunofluorescence analysis with oocysts was used as control. Although high levels of serum antibodies of the IgA class were detected in some donors in the group of healthy adults, elevated values were consistently found in HIV-infected patients. Higher values were found in HIV patients with clinical cryptosporidiosis. The presence of a secretory component in serum IgA antibodies in these patients has been documented. Data indicate that IgA serum antibodies are produced as well as IgM and IgG antibodies upon contact with the parasite, and suggest that elevated IgA serum antibodies to Cryptosporidium are not associated with protection in HIV patients.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised,double blind,placebo controlled trial.

OBJECTIVES--To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN--Randomised, double blind, placebo controlled trial. SUBJECTS--74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES--Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS--The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION--Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Intensity of the production of rheumatoid factor in patients with different degrees of sensitization to Borrelia garinii antigens

The content of rheumatoid factor and the levels of IgA, IgM, IgG in patients with different degrees of sensitization to Borrelia garinii antigens were studied. The titer of rheumatoid factor was found to increase in accordance with the growth of the levels of anti-Borrelia antibodies. A rise in the concentration of serum immunoglobulins simultaneously with the development of Borrelia infection was registered. The mechanisms of autoimmunization are discussed, taking into account the known biological properties of the causative agent of Lyme disease.     

Bacterial flora from bronchoalveolar lavage and occurrence of class IgG and IgA antibodies to Chlamydia pneumoniae in patients with chronic obstructive pulmonary disease (COPD)

Bronchoalveolar lavage taken from 46 patients (ranging in age from 21 to 71 years, mean 50.6 +/- 13.9) was examined for aerobic and anaerobic bacterial flora. Sera taken from 39 of patients as well as sera taken from 25 healthy blood donors of similar age (P = 0.99) were examined to determine IgG and IgA antibodies to C. pneumoniae. Bacterial flora was routinely cultured and determined using ATB computer system (bioMérieux,). IgG and IgA antibodies were tested by the enzyme immunoassays (Labsystems, Finland, Helsinki). Sera containing anti -C. pneumoniae IgG antibodies with titers of 45 EIU or higher and IgA with titers of 12 EIU or higher were considered positive. 143 of aerobic and 74 of anaerobic bacterial strains were cultured. Streptococci group viridans, pneumococci, enteric bacilli, Haemophilus spp., Prevotella spp., Actinomyces spp., Bifidobacterium spp. and Veilonella spp. were most often cultured. 66.6% of patients had IgG or IgA antibodies, in contrast, to the control group in which 60.0% and 44.0% of examined blood donors had IgG and IgA antibodies respectively. COPD patients were more frequently positive for specific anti-C. pneumoniae antibodies than the healthy donors (p = 0.003). The difference in a seropositivity rate of specific IgA and IgG antibodies was significant (p = 0.00002 and p = 0.003 respectively). Bronchoalveolar lavage of patients suffering from COPD can be contaminated with high number of aerobic and anaerobic bacterial species, and immunological status of the patients indicated persistent infection caused by C. pneumoniae more often than in controls.     

Intensity of the humoral immune response to herpesviruses as an indicator the body immune deficiency

The state of the local immunity system of the oral cavity was studied by the level of saliva immunoglobulins in patients with different processes on their mucous membranes: herpetic infection, respiratory allergosis and malignant tumors of the mouth cavity and the laryngopharynx. The suppression of the production of sIgA, was accompanied by the enhanced production of antibodies to the most widespread herpesviruses (herpes simplex virus, cytomegalovirus and Epstein-Barr virus). The maximum levels of serum IgG to herpesviruses were determined in patients with malignant tumors. The role of herpesviruses in the pathogenesis of immunodeficient states is discussed.     

Genital herpes simplex.

Genital herpes is a sexually transmitted disease caused by the herpes simplex virus. Following the initial infection the virus becomes latent in the sacral ganglia. Approximately 80% of patients are then subject to milder but unpredictable recurrences and may shed the virus even when they are asymptomatic. The disorder causes concern because genital herpes in the mother can result in rare but catastrophic neonatal infection and because of a possible association between genital herpes and cancer of the cervix. No effective treatment is as yet available. Weekly monitoring for virus by cervical culture from 32 weeks'' gestation is recommended for women with a history of genital herpes and for those whose sexual partner has such a history.