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PubMed1975

The immunology of asbestosis.

Forty-one employees with varying degrees of asbestosis have been tested for any alteration in the immunological profile. Of these, twenty-two employees showed evidence of pleural thickening and nineteen parenchymal asbestotic fibrosis. Those employees showing pleural thickening gave a strong reaction to different skin tests and a few of those with a parenchymal asbestotic fibrosis showed depressed cutaneous reactivity. Lymphocytotoxic antibodies were present in the sera of 60% of those with pleural thickening and 94% of those with parenchymal asbestosis. An immunological screening schedule is suggested for those employees who show pleural thickening.

Asbestosis↗

PubMed1972

Effect of transfer factor on lymphocyte function in anergic patients.

Dialyzable transfer factor, obtained from frozen-thawed peripheral blood leukocytes from a single donor, was given to five anergic patients with chronic mucocutaneous candidiasis. Studies of immunological responses including delayed cutaneous hypersensitivity, in vitro antigen-induced thymidine incorporation, and production of macrophage migration inhibition factor (MIF) were conducted both before and after injection of transfer factor. Before transfer factor, none of the patients had delayed skin responses to any of the natural antigens studied. Their lymphocytes did not produce MIF after exposure to antigens in vitro and only one patient showed increased thymidine incorporation when his lymphocytes were cultured with candida and streptokinase-streptodornase (SK-SD). After injection of transfer factor, four patients developed delayed skin responses to antigens to which the donor was sensitive; no recipient reacted to an antigen to which the donor was nonreactive. Lymphocytes from recipients produced MIF when cultured with antigens that evoked positive delayed skin tests. Only one patient developed antigen-induced lymphocyte transformation and this response occurred only intermittently. Attempts to sensitize three of the patients with the contact allergen, chlorodinitrobenzene, both before and after transfer factor, were unsuccessful. The fifth patient, a 9-yr old boy with an immunologic profile similar to the Nezelof syndrome, did not become skin test-reactive or develop positive responses to the in vitro tests. These findings suggest that transfer factor acts on the immunocompetent cells that respond to antigens with lymphokine production, but has little, if any, effect on cells that respond to antigens by blastogenesis. The failure to sensitize the subjects with chlorodinitrobenzene illustrates the specificity of the immunologic effects of transfer factor, and implies that it does not function through nonspecific, adjuvant-like mechanisms. Failure of transfer factor to produce positive skin tests or MIF production in a patient with Nezelof's syndrome may be evidence that lymphokine-producing cells are thymus derived.

Adult↗

PubMed1990

Hodgkin's disease followed by lymphomatoid papulosis. Immunophenotypic evidence for a close relationship between lymphomatoid papulosis and Hodgkin's disease.

The clinical association of lymphomatoid papulosis and Hodgkin's disease and the striking morphologic similarity of atypical cells in lymphomatoid papulosis to Reed-Sternberg cells in Hodgkin's disease suggest that lymphomatoid papulosis and Hodgkin's disease are related. To test this possibility we studied the antigenic profile of Reed-Sternberg cells in the lymph nodes and of atypical cells in cutaneous lesions of lymphomatoid papulosis in two patients with Hodgkin's disease and lymphomatoid papulosis. In paraffin sections both cell types expressed CD30, CD45 T cell-restricted antigens, and occasionally CD15 antigens. They were negative for CD45 B cell-restricted antigens and for lysozyme. In cutaneous lymphomatoid papulosis lesions a similar immunologic profile of the atypical cells was found; that is, they were positive for CD30, CD2, CD3, and CD25 but negative for B cell and macrophage antigens. The similarity of the immunophenotype of Reed-Sternberg cells in lymph nodes affected by Hodgkin's disease and the immunophenotype of atypical cells of lymphomatoid papulosis lesions in the same patients suggests that the malignant cells in both conditions are derived from activated T cells and that they are closely related if not identical.

Adult↗

PubMed1996

The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury.

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.

Animals↗

PubMed2002

Increased IgG 3:4 ratios in adolescent antisocial females: evidence of Th1/Th2 imbalance?

Female antisocial behavior in adolescence and late childhood has been associated with low basal cortisol levels. Because low cortisol has also been correlated with T helper cell Type 1 (Th1) predominance and suppression of T helper cell Type 2 (Th2), we investigated whether adolescent antisocial girls demonstrated this immunologic profile. Using plasma levels of IgG3 and IgG4 as markers for Th1 and Th2 activity, we studied IgG 3:4 ratios in 16-year-old girls with conduct disorder (CD) (n=42) or no psychiatric disorder (normal controls (NC)) (n=35). The mean IgG 3:4 ratio was higher in the CD group; this relationship remained significant after controlling for the effects of other variables. These data indicate that immunologic abnormalities are present in adolescent antisocial girls. Future studies should measure cytokine levels and investigate the clinical implications of these findings.

Adolescent↗

PubMed1979

[Down syndrome: immunological study in adults (author's transl)].

The immunological profile was evaluated in 12 adults affected by Down's syndrome. Our findings showed: increase of serum IgG, IgA and Gammaglobulins, decrease of IgM, presence of auto-antibodies and increased antibodies response after antigenic stimulation (typhoid vaccination). Some tests, connected with T lymphocytes functions, were also abnormal: percentage of E-active rosettes, cutaneous sensibilization with DNCB and lymphocyte stimulation index with PHA. Our findings suggest a T lymphocyte deficit, with loss of immunological surveillance and therefore of the control over antibody mediated immunological reactions. The immunological alterations observed in our adult patients with Down's syndrome were more extensive and severe than those found in young subjects. The possible relevance of these findings is discussed as well as the incidence of Alzheimer's dementia in adult patients with Down's syndrome.

Adult↗

PubMed1985

An enzyme-linked immuno-filtration assay used to compare infant and maternal antibody profiles in toxoplasmosis.

Enzyme-linked immuno-filtration assay is carried out on a micropore membrane. This doubly analytical technique permits simultaneous study of antibody specificity by immunoprecipitation and characterisation of antibody isotypes by immuno-filtration with enzyme-labelled antibodies. Recognition of the same T. gondii antigenic constituent by IgG, IgA, IgM or IgE antibodies produces couplets (IgG-IgM; IgG-IgA) or triplets (IgG-IgM-IgA; IgG-IgM-IgE) which identify the functional fractions of the toxoplasmosis antigen. In acquired toxoplasmosis, the persistence of IgM antibody long after infestation puts in question the implication of recent infestation normally linked to detection of this isotype. For sera of comparable titres, comparison of immunological profiles by the method described demonstrates disparities in the composition of the specific antibody content as expressed in international units. Use of the same method to detect IgM antibodies or distinguish between transmitted maternal IgG and IgG antibodies synthesised by the foetus or neonate makes a diagnosis of congenital toxoplasmosis possible in 85% of cases during the first few days of life. With the method described the diagnosis may be made on average 5 months earlier than with classical techniques. In the course of surveillance for latent congenital toxoplasmosis, the appearance of IgM or IgE antibodies raises the possibility of complications (hydrocephalus, chorioretinitis). After cessation of treatment, a rise in IgG antibodies indicating persistence of infection is detected earlier by the present than by classical methods.

Antibodies↗

PubMed2004

Efavirenz versus nevirapine in current clinical practice: a prospective, open-label observational study.

An open-label, observational, prospective 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors (NNRTIs) in all possible indications of current clinical practice. A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability (with special emphasis on metabolic and hepatic toxicity) were measured in 287 evaluable patients treated with efavirenz, compared with 258 subjects taking nevirapine for 18 months. A separate efficacy analysis was performed in 154 antiretroviral-naive subjects, 298 patients experienced with 2-7 prior anti-HIV lines who abandoned protease inhibitors (PIs), and 103 subjects entering a salvage regimen containing at least 4 drugs, including PIs. Antiretroviral-naive patients experienced greater efavirenz activity at 3-12 months (maximum HIV RNA drop =-2.4 log(10) copies/mL), associated with a significantly higher rate of complete viral suppression, while immunologic results proved significant only after 6-9 months. When assessing experienced patients and those on rescue regimens, a similar and progressively blunted laboratory response was achieved, on the ground of a worse baseline virologic and immunologic profile, and duration of prior anti-HIV therapy. Both first-month (4.2 and 4.3% for efavirenz and nevirapine, respectively) and overall discontinuation rates (11.5 and 12%, respectively) proved similar, but a profound difference emerged as to the different spectrum of untoward events: central nervous system (CNS) disturbances, persisting metabolic abnormalities, and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity (regardless of chronic infection with hepatitis B or C virus and methadone use) for nevirapine. A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients, whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison. Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable, the different pathways prompting allergic, metabolic, liver, and CNS disturbances observed with NNRTIs deserve careful investigation, to prevent toxicity of these relevant antiretroviral compounds.

Adult↗

PubMedDate not supplied

Immunological abnormalities of acquired immunodeficiency syndrome and related disorders in patients from Rio de Janeiro, Brazil.

The immunological profile of acquired immunodeficiency syndrome (AIDS) and chronic lymphadenopathy syndrome (CLAS) in 15 and 11 Brazilian patients, respectively, was studied. The AIDS patients showed reduced percentage of total T (CD3) and T-helper-inducer (CD4) lymphocytes, relative increase in numbers of T-suppressor-cytotoxic (CD8) cells and a marked inversion of T-helper-inducer/suppressor-cytotoxic (CD4/CD8) ratio. Lymphoproliferative responses to PHA, ConA, PPD and PWM were diminished. Hypergammaglobulinemia and high levels of circulating immune complexes were also found. The CLAS patients also showed important immunological alterations, but not so intense as those with AIDS. These data seems to be similar to those observed in other parts of the world.

AIDS-Related Complex↗

PubMed1991

[Predicting insulin-dependent diabetes. Study of risk markers].

The presence of specific antibodies at the time of clinical diagnosis, together with genetic susceptibility and animal models of spontaneous diabetes obtained by immunological destruction of insulin-secreting cells, suggests that insulin-dependent (type I) diabetes is an autoimmune disease. Prospective studies conducted among first-degree relatives of type I diabetes patients or in the general population have identified 3 types of markers appearing during subclinical destruction of islet cells, or pre-diabetes, which can be used to detect subjects at high risk. These are: high-titer anti-islet antibodies (ICA), anti-insulin autoantibodies and early insulin response to intravenous hyperglycaemia. Owing to the great heterogeneity of metabolic profiles, immunological markers alone cannot predict the time when insulin-dependence will occur. The psychological impact of these studies is such that they should be carried out only in specialized centres. Identifying pre-diabetes is important for the prevention of the disease. Until immunomodulators devoid of side-effects are available, pre-diabetes is a good period to train the patients and start insulin therapy when it becomes necessary.

Autoantibodies↗

PubMed1998

The role of the T lymphocytic cell cycle and an autogenous lymphocytic factor in clinical medicine.

In this study 315 individuals (25 controls, 290 chemically sensitive immunocompromised patients) were investigated. Each patient had been on a standard therapy of avoidance of pollutants, nutritional supplementation, and injections of antigens for foods, and biological inhalants, but did not attain their immunological competence. Peripheral lymphocytes were collected and DNA histograms were constructed. The flow cytometer was used to evaluate the cell cycle, haematological, and other immunological profiles. From the other portion of the blood specimen, lymphocytes were propagated in vitro, harvested, and a lysate, termed the autogenous lymphocytic factor (ALF), was prepared. When treated with ALF, 88% of these individuals showed a significant (p < 0.001) clinical improvement which correlated with laboratory findings, involving regulation of abnormal cell cycles, increase in total lymphocytes and subsets T4, T8, (p < 0.05) and cell mediated immunity (CMI) response (p < 0.001). The ALF presumably acts as a biological response modifier. The cell cycle and ALF provide clinical tools for diagnosis and regulation of immunological incompetence.

Cell Cycle↗

PubMed2005

Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study.

Organ donors with a serologic profile of recovered (HBsAg negative and/or anti-HBc IgG positive) hepatitis B virus infection (HBV) have been reported to transmit HBV to recipients. In Italy, up until 2002, anti-HBc determination was not mandatory. We retrospectively evaluated the incidence of HBV transmission among recipients transplanted with organs from anti-HBc positive donors from 1997 to 1999. Anti-HBc was screened in 886 available sera among 964 HBsAg and anti-HCV negative donors. HBV transmission was evaluated in 325 kidney, liver, and heart recipients according to their pretransplant HBV serum profile. Of 210 anti-HBc positive donors, 185 were anti-HBc positive/anti-HBs positive and 25 anti-HBc positive/anti-HBs negative with a prevalence of 20.8% and 2.8%, respectively. One hundred seven sera (51%) were collected from donors after transfusion of blood components, the remainder were either before transfusion or from nontransfused donors. The 210 anti-HBc positive subjects donated 356 kidneys, 117 livers and 117 hearts, among whom follow-up is presently available for 251 kidney, 61 liver, and 25 heart recipients. No HBV transmission was observed independent of the recipient immunological profile among the kidney or heart recipients. In liver recipients, no transmission was reported in recovered or vaccinated patients, while a high incidence (43%) of de novo hepatitis was observed among naive patients. In conclusion, there does not seem to be a risk of transmitting HBV through anti-HBc positive transplants in heart and kidney recipients; only naive liver recipients are at high risk of HBV infection.

Antibodies, Viral↗

PubMed1994

[Defects in cellular immunity in patients with dermatophytosis].

The authors examined in a group of 24 patients with epidermophytosis, refractory to general and local antimycotic treatment, persisting for 2-4 years, the immunity profile and compared the results with those in a group of healthy subjects. Epidermophytosis was diagnosed on the basis of the clinical picture, microscopic and cultivation examinations. The authors revealed in the patients with epidermophytosis a defect in the cellular immunity component, while there was no defect in the humoral component. They revealed also a shift in the proteins of the inflammatory phase which confirmed the long-term inflammatory process of the disease. In the conclusion the authors recommend to examine in patients with prolonged epidermophytosis refractory to general and local antimycotic treatment the immunological profile, and if there is a defect of cellular immunity despite antimycotic treatment to administer also immunostimulating preparations.

Adolescent↗

PubMed2026

A distinct psoriasis-atopic dermatitis overlapping phenotype in adults with dual type 2 and type 3 immune features and favorable response to Janus kinase 1 inhibition.

BACKGROUND: Patients exhibiting overlapping histopathologic features of psoriasis (Pso) and atopic dermatitis (AD) present a diagnostic and therapeutic challenge. OBJECTIVES: To delineate the clinicopathological and immunologic portrait of psoriasis-atopic dermatitis overlapping (Pso-Ec) for integrated diagnosis and therapeutic decision-making. METHODS: We conducted a 2-center prospective study comparing 30 Pso-Ec patients with typical Pso and AD cohorts. Clinicopathological characteristics and immunologic profiling of lesional skin and peripheral blood were analyzed, and treatment courses were assessed. RESULTS: Pso-Ec patients (aged 13-72 years; mean age: 49.7 years) presented with ill-defined erythematous plaques with thin scales, excoriation, intense itching, and mixed psoriatic-eczematous histology. Immune profiling showed co-existence of helper T cell 2/cytotoxic T cell 2 and helper T cell 17/cytotoxic T cell 17 in skin and blood, with Janus kinase (JAK) 1 signal transducer and activator of transcription 2/6 signaling involvement. Responses to prior Pso-targeted (n = 18) and AD-targeted (n = 15) biologics were often inadequate. In contrast, JAK1 inhibitors achieved minimal disease activity (body surface area ≤ 2, numerical rating scale ≤1) during a median follow-up of 17 months. No progression to classic Pso or AD phenotypes was observed. LIMITATIONS: Sample size was limited and immunologic analyses were performed in a representative subset of patients. CONCLUSIONS: Pso-Ec represents a distinct, predominantly adult-onset phenotype driven by dual type 2 and type 3 inflammation, and JAK1 inhibitors appear as an effective option.

Humans↗

PubMed2002

Update on cancer vaccines.

The development of vaccines to induce tumor-specific immunity in patients with cancer has as emerged as a major area of investigation. The identification of antigens uniquely expressed by tumor cells and a heightened understanding of tumor immunology have resulted in efforts to activate host immunity to recognize and reject tumor cells. Tumor-associated antigens and peptides, genes encoding tumor antigens, and modified whole tumor cells have been used in preclinical studies with provocative results. Potent antigen-presenting cells, known as dendritic cells, have also been modified using peptides, genetic material, or whole tumor cells to present tumor antigens in the context of co-stimulation to overcome tolerance and induce tumor-specific cell killing. Promising data generated from the preclinical evaluation of cancer vaccines have resulted in the initiation of clinical trials to define the associated toxicity profile, immunologic response, and clinical impact of this treatment approach. We summarize the preclinical and clinical experience in this expanding area of investigation. Cancer vaccines hold much promise; however, many unresolved questions remain in the effort to generate a clinically meaningful treatment strategy.

Journal Article↗

PubMed1987

Immunological effects of isoprinosine as a pulse immunotherapy in melanoma and ARC patients.

Immunomodulatory effect of Isoprinosine are presented in melanoma and HTLV-III/LAV infected patients. Isoprinosine (50 mg/kg) was used as a pulse immunotherapy according to two different schedules: A) 5 days every 15 days and B) 5 days every 15 days for 2 months, then 5 days every 2 months. The patients' immunological profiles were tested before and during the treatment in terms of T-cell subsets, cell number requirement for PHA-induced proliferation, and delayed hypersensitivity reaction to recall antigens. Primary malignant melanoma patients are randomized between surgery alone or associated to isotherapy (schedule A or B). Schedule A, after an initial improvement of surgery-induced immune deficiency, is responsible for an immunodepression, whereas schedule B determines a prolonged restoration in immune responses in melanoma and AIDS related complex or Kaposi sarcoma patients as well. In vitro effects of Isoprinosine on HTLV-III/LAV infection are presented. These data exhibit 1) the need of an immunological follow-up during isotherapy and 2) the immunological benefit of a pulse immunotherapy during acquired immunodeficiencies related to cancer surgery or to HTLV-III/LAV infection in man.

Acquired Immunodeficiency Syndrome↗

PubMed1982

Incipient resistance of Plasmodium falciparum to chloroquine among a semi-immune population of the United Republic of Tanzania. 2. The impact of chloroquine used as a chemosuppressant on the immune status of the population.

Decreased sensitivity and incipient resistance of Plasmodium falciparum strains to chloroquine have been reported from Mto-wa-Mbu, in the north-east of the United Republic of Tanzania. In this locality the population had been exposed to chloroquine pressure for about two decades, in the form of medicated salt and through easy availability of the drug itself. In an attempt to find out whether such chemosuppression had influenced the immune response of the population, two seroepidemiological surveys were carried out in March 1981 and March 1982; the second survey was performed to confirm the results obtained in the first one. The humoral immunological response was measured by the immunofluorescent antibody technique. In the absence of information on the immunological profile that existed in the area prior to the introduction of chloroquine in 1960, the results of the present surveys were compared with those obtained in another locality in the north-east of the United Republic of Tanzania in 1967, and in the West Kiang district of Gambia in 1965. The two areas used for comparison exhibited a malaria endemicity similar to that prevailing in Mto-wa-Mbu prior to the introduction of the medicated salt. The results from Mto-wa-Mbu showed a significantly lower proportion of subjects with positive titres and a lower geometric mean titre in all age groups.A reduction in the humoral immunological response might be explained by the drug pressure that has been exerted in the area for many years. The depressed immune response found at Mto-wa-Mbu, however, was so marked that other factors may have contributed to its establishment.In view of the importance of these findings, it is recommended that further, longitudinal serological studies be conducted in the field to assess the effects of chemosuppression on the immune response of the protected populations.

Anopheles↗

PubMed1991

Systematization of clinical management for recurrent aborters by combined immunological testing.

The natural outcomes of successive new pregnancies of 66 recurrent aborters were analysed in relation to their immunological profiles. The data demonstrated that the presence of anti-phospholipid antibodies (success rate 6.7%), positive anti-paternal cytotoxicity (8.7%) and a negative mixed lymphocyte reaction (MLR)-blocking effect (33.3%) in the patients' sera were factors associated with a poor prognosis. By the combined evaluation of these testings, a rational scheme of clinical management for recurrent aborters was established.

Abortion, Habitual↗