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Immunological profiles in alopecia areata.

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

Adolescent↗

Prospective immunological profiling in a case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).

IPEX syndrome is a genetic autoimmune disease characterized by immune-mediated polyendocrinopathy, enteropathy, and X-linked inheritance. We describe a case of IPEX in which lymphocyte phenotypes were assessed at birth, before initiation of Cyclosporin A therapy, and at frequent intervals to 18 months of age. We performed flow cytometry for lymphocyte subtypes and for activation markers (HLA-DR, CD25, and CD69 or CD71). The ratios of both T to B cells and CD4+ to CD8+ cells were elevated at birth, but CD4+ cells were not activated. HLA-DR+ and CD25+ activated T-cells increased in association with two episodes of clinical deterioration: colitis and the onset of type I diabetes mellitus. These results indicate that measures of activation, particularly HLA-DR+ and CD25+ frequency, correlate well with the development of early active disease and may presage clinical episodes. Continuous maintenance of immunosuppression, once started, appears critical for prevention of permanent tissue damage.

Follow-Up Studies↗

Immunologic profile of patients with cured Hodgkin's disease.

Blood lymphocytes from 9 patients with Hodgkin's disease (HD) were studied. The results were compared with those of 6 seminoma testis patients and 9 healthy unrelated controls. All patients were in complete and unmaintained remission more than 10 years after termination of radiotherapy. The mean T-lymphocyte count of HD patients was lower than that of controls and seminoma testis patients. Lymphocyte DNA synthesis induced by pokeweed mitogen and phytohaemagglutinin was normal in both patient groups. Concanavalin A-induced DNA synthesis was low in 4 patients with HD although the mean stimulation of the group did not differ from controls or seminoma testis patients. Lymphocyte activation by PPD was slightly decreased in the 2 patient groups. No increase in spontaneous lymphocyte DNA synthesis was observed. The responding and stimulatory capacity in mixed lymphocyte culture was decreased in 3 and 2 HD patients respectively. 4 out of the 9 patients with HD but none with seminoma testis displayed severe impairment in T-lymphocyte functions. As 1 of the 4 had been treated solely by surgery, late effects of irradiation can only partly explain the results. The results may favour a hypothesis postulating a constitutional defect contributing to the immunoincompetence in HD.

Adolescent↗

Clinical, microbiological and immunological profile of healthy, gingivitis and putative active periodontal subjects.

Thirteen periodontally healthy subjects were monitored clinically for 6-12 months. Clinical measurements at 6-weekly intervals included duplicate PD measurements, presence of plaque, redness, and bleeding on probing. Baseline measurements consisted of 2 visits 1 wk apart. Microbial samples were taken from 11 of the subjects who had completed at least 8 months of monitoring. Levels of serum antibodies to 12 periodontal species were determined from 10 subjects. Standard deviations of replicate PD measurements, computed for each subject, ranged from 0.2-0.3 mm over the monitoring period. Plaque and redness increased during monitoring, and showed a weak association with PD change. Baseline and follow-up distributions of PD changes indicated that changes of > 1.5 mm could reasonably be considered to represent active sites. Five subjects demonstrated at least 1 site deepening by 1.5 mm over the period monitored, and these were considered putative active subjects. Sites from 2 subjects showed PD increases in the 6 wk just before sampling, and these were considered to represent active sites. Species associated with putative active subjects included Actinomyces naeslundii, Veillonella parvula, Selenomonas noxia and Prevotella nigrescens. Streptococcus sanguis, S. gordonii and Peptostreptococcus micros were associated with inactive subjects. S. gordonii and S. oralis were associated with health, whereas P. nigrescens was associated with gingivitis. Elevated serum antibodies were detected to A. actinomycetemcomitans in 4 subjects. The predominant microbiota of putative active subjects included some species previously associated with gingivitis, and some species previously associated with progressing periodontitis.

Adult↗

Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation.

Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T(0)-T(2)) to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T(2) (p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T(2) (p < 0.05). EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T(2) (p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.

Anti-Inflammatory Agents↗

Incipient ovarian failure and premature ovarian failure show the same immunological profile.

PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failure. METHOD OF STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients, 50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did not differ between the groups. There was a statistically significant difference in lymphocyte subsets between the control group and the POF group, with the IOF group taking an intermediate position. We found a decrease in percentage of T-suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in natural killer cells, and an increase in B lymphocytes and HLA-DR positive T cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form of POF. The question remains whether these changes are the cause or the consequence of the ovarian failure.

Adult↗

Immunological profiles of patients from endemic areas infected with Schistosoma mansoni.

Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided rather distinct profiles of responses in different types of patients. In general it is clear that patients with early infections respond strongly to SEA while response to SWAP are develop more slowly. As infection progresses into the more chronic phases, a general pattern is seen which leads to lower anti-SEA proliferative responses in the face of higher responses to SWAP and variable anti-cerc responsiveness. Cured not re-exposed patients express very high levels of anti-SEA proliferation. It has recently been seen that those individuals who live in endemic areas and have continued water contact, but are repeatedly stool-negative (who are presumed to have self-cured or be putatively resistant; endemic normals) are strongly responsive to antigenic extracts, particularly to SEA. Furthermore, our results show that endemic normal individuals have significantly higher IFN gamma production upon PBMC stimulation with schistosome antigens than infected individuals. With the emergence of more studies it is becoming apparent that both the intensity and the prevalence of a given area may influence or shape the general responsiveness of the population under study.

Adolescent↗

Immunologic profile of juvenile periodontitis. I. Lymphocyte blastogenesis and the autologous mixed lymphocyte response.

Studies of blastogenesis of lymphocytes in culture from juvenile periodontitis (JP) patients have been inconclusive. Experiments demonstrating differences in lymphocyte blastogenesis to preparations of putative periodontopathogens in JP and phytohaemagglutinin (PHA) were performed. Variables in the blastogenesis assay system recently reported were controlled which included using a range of cell and activator concentrations, incubation times of 3, 5 and 7 days, conical-bottomed microtest wells and chemical inhibitors during labeling of DNA which permits accurate assessment of lymphocyte blastogenesis. Using these modified culture conditions, stimulated lymphocytes of localized (LJP) and generalized (GJP) forms of JP patients did not differ significantly from stimulated lymphocytes of healthy subjects in counts incorporated, stimulation index, incubation time, cell concentration or activator dose required for maximal blastogenesis to bacterial preparations of Actinobacillus actinomycetemcomitans (Y-4), Bacteroides gingivalis, Capnocytophaga ochraceus, Fusobacterium nucleatum, Streptococcus sanguis and Treponema denticola. Unstimulated lymphocyte cultures reflecting the autologous mixed lymphocyte response (AMLR) were increased for LJP compared to healthy subjects although not statistically significant. Unstimulated lymphocyte cultures of GJP were decreased compared to healthy subjects and LJP (P less than 0.05). These observations indicate that GJP patients may have abnormalities in T- and B-lymphocyte regulatory mechanisms.

Actinomyces↗

Immunologic profile of juvenile periodontitis. II. Neutrophil chemotaxis, phagocytosis and spore germination.

Patients with juvenile periodontitis (JP) were grouped into one of the two recognized forms of the disease: a localized form affecting incisors and first molars (LJP) and a generalized form affecting more than 14 teeth (GJP). The role of the neutrophil in the etiology and pathogenesis of LJP has recently been recognized. Experiments aimed at confirming previous information related to neutrophil chemotaxis defects in LJP were performed. Additional experiments aimed at demonstrating significant differences in phagocytosis of bacterial spores and inducing spore germination were also completed. Age- and sex-matched healthy subjects were used as "internal" controls (experiments run concomitantly). Peripheral blood neutrophils from 29 LJP, 24 GJP and 24 healthy subjects were assessed for chemotaxis. This assay was performed in a Boyden diffusion chamber using 10(-8) M N-formylmethionylleucylphenylalanine as chemoattractant. A chemotactic defect was defined being 2 standard deviations below the mean of healthy subjects. Twenty-three of 29 LJP (79%) and 14 of 25 GJP (58%) had a neutrophil defect. Peripheral blood neutrophil phagocytosis assays were performed in vitro using radiolabeled bacterial spores [45Ca]Bacillus cereus. Eighteen of 29 LJP (62%) and 7 of 24 GJP (29%) had a phagocytic defect. Neutrophil-induced spore germination assessed in vitro showed that 13 of 20 LJP (65%) and 3 of 8 GJP (38%) had this defect. These observations indicate that patients with JP have abnormalities in neutrophil functions of chemotaxis, phagocytosis and spore germination.

Adolescent↗

General anesthesia mode does not influence endocrine or immunologic profile after open or laparoscopic cholecystectomy.

To verify the impact on stress response and the influence of anesthesia on endocrine/immunologic changes, we have investigated the plasma level of norepinephrine, cortisol, TNFalpha, and IL-6 in 46 patients scheduled for laparotomy and laparoscopic cholecystectomy at 2, 6, 12, and 24 h after the operation. Among subjects who underwent open approach, 9 received fentanyl anesthesia and 13 received isoflurane anesthesia. In the laparoscopy group, 14 patients were given fentanyl anesthesia and 10 were given isoflurane anesthesia. The results obtained confirmed that laparoscopic cholecystectomy is associated with a lesser immunoendocrine response, and the two anesthesia models do not interfere with plasma changes of the assessed hormones and cytokines.

Anesthesia, General↗

Immunological profile of treated lepromatous leprosy patients.

The immune responses of 19 treated lepromatous patients who had remained smear negative for a long period were assessed for specific cell-mediated immunity (CMI), anti-Mycobacterium leprae antibodies and cytokine release in response to challenge with M. leprae soluble antigen (MLSA). All of these patients remained anergic to Mitsuda lepromin. Lymphoproliferation in response to M. leprae antigen was noted in only two patients. Significant reduction in the phenolic glycolipid I (PGL-I) antibody response in treated patients with no difference in the M. leprae 35-kDa antibody response was observed when these responses were compared with those of active lepromatous patients. More treated patients produced interleukin-2 (IL-2) and interferon gamma (IFN-gamma) than did active patients. On the other hand, fewer treated patients produced IL-10 than did active patients. These limited findings suggest that the host immune response makes an attempt toward upregulation of CMI in some treated LL/BL patients.

Adult↗

Effect of bacterial extracts on the immunologic profile in chronic relapsing brucellosis patients.

Brucellosis is an intracellular bacterial disease of common incidence in Greece. Existing therapy is inadequate and a considerable proportion of patients become chronically ill and are immunocompromised. Defects of the monocyte-macrophage system and T-lymphocytes have been described in chronic brucellosis and can be restored after immunopotentiation therapy. Bacterial (Klebsiella pneumoniae) extracts exert immunostimulating effects on the monocyte-macrophage system and have already been used successfully in the prevention of common infections of the respiratory track. So we decided to investigate: 1) Leukocyte Migration Index (LMI), 2) Monocyte-macrophage random and directed migration against both nonspecific leukoattractant (casein) and disease specific antigens (Brucella melitensis, Brucella abortus), 3) Monocyte-macrophage phagocytosis index, 4) Delayed-type hypersensitivity (skin tests) against seven antigens, before (TO), during (T2), and after (T3) oral administration of bacterial (Klebsiella pneumoniae) extracts at conventional doses plus antibiotics or not. Our results show that: 1) Concerning the LMI, 4 out of 19 remained anergic at time T3 of the study, 2) Random migration was not affected during treatment, 3) Directed migration increased significantly without reaching control group values, 4) Phagocytosis index increased significantly and reached normal values at T3, 5) Delayed type hypersensitivity reactions (skin tests) increased significantly at the end of the study period. Reaction against Tuberculin and Candida antigens showed the most pronounced increase in skin reactivity. In conclusion, bacterial (Klebsiella pneumoniae) extracts improve peripheral monocyte locomotion and restore phagocytosis index, thus enhancing cellular immunity parameters in immunocompromised chronic brucellosis patients.

Journal Article↗

Multiple myeloma: an immunologic profile. II. Bone marrow studies.

Bone marrow mononuclear cell populations were studied in 35 patients without myeloma, 39 patients with multiple myeloma, and 15 patients with benign monoclonal gammopathy. Bone marrow mononuclear cell receptors, responses to mitogens or allogeneic stimuli, and suppressive effects on in vitro peripheral blood lymphocyte (PBL) function were studied. In bone marrow cell populations from patients with untreated multiple myeloma, the percent of complement receptor-bearing cells and the pokeweed mitogen- and concanavalin A-stimulated responses were significantly greater than were those in bone marrow cell populations from patients without myeloma. Sheep red blood cell receptor-bearing cells were significantly greater in marrow populations from treated multiple myeloma patients compared to those from untreated multiple myeloma patients. Sheep red blood cell receptor-bearing cells from the bone marrow of multiple myeloma patients suppressed responses of the multiple myeloma patients' PBL's to autologous mitomycin C-treated bone marrow plasma cells and to allogeneic stimuli in one-way mixed leukocyte culture. Complement receptor-bearing cells suppressed the response to pokeweed mitogen. The presence of lymphocytes in the marrow compartment that are capable of suppressing the response of myeloma patients' PBL's to plasma cell antigens may be significant in the pathogenesis of multiple myeloma.

Bone Marrow↗

Incidence & immunological profile of multiple myeloma patients.

Multiple myeloma was diagnosed in 84 residents of Jammu & Kashmir between 1984-1988. The data were analyzed for variations of demographic factors, ethnicity and location of residence (urban/rural). The average annual incidence per 100,000 residents was 1.28. The rates for males and females were 2.02 and 0.71 per 10(5) persons/year respectively. The average incidence rate for Muslims was significantly higher than that for Hindus. Urban residents had significantly higher rates than rural population. Highest incidence rate (14.39) was in the age group of 65 yr and above.

Adult↗

Immunological profiles in workers occupationally exposed to inorganic mercury.

Forty-one male mercury-exposed workers were examined for the serum concentration levels of immunoglobulins (IgG, IgA, IgM), alpha-1-antitrypsin (A1AT), alpha-2-macroglobulin (A2M), ceruloplasmin (CPL) and orosomucoid (ORO). In the period preceding this investigation the mercury concentrations in workplace air ranged from 0.106 to 0.783 mg.m-3, the range of urinary mercury concentrations was from 0.029 to 0.545 mg.1(-1). All but two (IgG and A1AT) of the immune parameters tested were at the levels that were evidently higher than those found in a control group of 55 workers matched by age who lived in a relatively clean area. The percentage of individuals with no value out of the range of normal physiological limits was in the controls almost 80%, in the exposed 36.6% only. These findings confirm the literature data which show that an inhalation exposure to inorganic mercury may evidently have a stimulating effect on some serum proteins in humans.

Analysis of Variance↗