The mediating role of alexithymia in the relationship between affective temperament and craving: Cross-sectional study conducted in a sample of bipolar and alcohol use disorder patients.

BACKGROUND: Bipolar disorder (BD) and alcohol use disorder (AUD) commonly co-occur and their interplay is influenced by several factors. Alexithymia is connected to BD and AUD; affective temperaments serve as risk factors for both; craving contributes to the development and maintenance of AUD. The present study tested whether alexithymia play a mediating role in the relationship between affective temperaments and craving in alcoholic bipolar patients. METHODS: 151 alcoholic bipolar patients (38 % females, mean age: 45.69 ± 9.04 years) were enrolled. The Mini International Neuropsychiatric Interview (MINI), the Brief Psychiatric Rating Scale (BPRS), the Toronto Alexithymia Scale (TAS-20), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego scale (TEMPS-A), and the Typology Craving Questionnaire (CTQ) were administered. Correlations among TAS-20, TEMPS-A, CTQ were conducted. Regression analyses were applied to verify the mediating hypothesis. RESULTS: Difficulty in identifying feelings mediated the association between anxious temperament and craving (Indirect effect: 0.42, BCaCI: 0.22-0.69), cyclothymic temperament and craving (Indirect effect: 0.55, BCaCI: 0.30-0.87), irritable temperament and craving (Indirect effect: 0.45, BCaCI: 0.19-0.80). TAS-20 difficulty in communicating feelings to others mediated the association between anxious temperament and craving (Indirect effect: 0.20, BCaCI: 0.06-0.41). LIMITATIONS: The sample size did not allow subgroup analyses. Data were collected cross-sectionally and in a single center. We did not investigate whether BD or AUD occurred first, although it might influence the mediation role of alexithymia. CONCLUSION: Among alcoholic bipolar patients, assessing and targeting alexithymia may be useful to modulate craving and, in turn improve, the general mental status of patients.

Clinical management of short children with low serum immunoglobulin but no immunodeficiency features.

BACKGROUND: In children of different ages investigated for failure to thrive, low (below the cut-off for age) immunoglobulin (Ig) values can be detected, without any clinical evidence of humoral immunodeficiencies. To better characterize infants presenting with diminished immunoglobulin levels, we studied IgG subclasses, in vitro Ig production and B cell subpopulation. METHODS: We monitored 17 children (12 boys and five girls, age range 1-18 years) with low serum levels of one or more Ig isotypes but without any clinical or laboratory features of immunodeficiency. RESULTS: Low IgM levels were frequent (52.9%). During the follow up, six of 17 cases (35.3%) normalized their immunoglobulin levels. Frequently, in the observed patients, low levels of immunoglobulins were not limited to the period of infancy. In all patients, in vitro Ig production and B lymphocyte subpopulations were within normal ranges. CONCLUSIONS: We suggest a quantification of serum Ig levels in children who fail to thrive in order to identify patients with low Ig levels. These children should be monitored until Ig levels normalize to exclude any immunodeficiency status. Early recognition of children with persistent hypogammaglobulinemia would allow prompt and appropriate clinical interventions.

Phenotypical/functional characterization of in vitro-expanded mesenchymal stromal cells from patients with Crohn's disease.

BACKGROUND AIMS: Because of their capacity to modulate the immune response and promote tissue repair, mesenchymal stromal cells (MSC) represent a potential novel treatment for autoimmune/inflammatory diseases, including Crohn's disease (CD). The aim of the study was in vitro characterization of MSC from active CD patients for future clinical application. METHODS: MSC from the bone marrow (BM) of seven CD patients (median age 32 years) were expanded ex vivo in the presence of 5% platelet lysate; cells were investigated for clonogenic efficiency, proliferative capacity, morphology, immunophenotype, differentiation potential, genetic stability and ability to suppress in vitro proliferation of both autologous and allogeneic lymphocytes to polyclonal mitogens. Results were compared with those of BM MSC of four healthy donors (HD). RESULTS: MSC were successfully expanded from all patients. Colony-forming unit-fibroblast (CFU-F) frequency and proliferative capacity were comparable in CD and HD MSC. CD MSC showed typical spindle-shaped morphology and differentiated into osteoblasts, adipocytes and chondrocytes. Surface immunologic markers did not differ between CD and HD MSC, with the only exception of sizeable levels of HLA-DR at early culture passages [12-84% at passage (P)1] in the former. CD MSC ceased their growth at variable passages (from P8 to P25) and entered senescence without any change in morphology/proliferation rate. Array-comparative genomic hybridization demonstrated that CD MSC do not show imbalanced chromosomal rearrangements. Both CD and HD MSC inhibited in vitro proliferation of lymphocytes to mitogens. CONCLUSIONS: CD MSC show biologic characteristics similar to HD MSC and can be considered for anti-inflammatory and reparative cell therapy approaches in patients with refractory disease.

Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation.

BACKGROUND: Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. METHODS: To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. RESULTS: We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. CONCLUSIONS: Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.

Children with recurrent otitis show defective IFN gamma-producing cells in adenoids.

Infectious diseases are frequently observed in children and their recurrence represents a demanding challenge for the paediatrician. It has been hypothesized that a defective immune response may occur in these patients. The aim of the present study was to evaluate whether children presenting with recurrent otitis have a defective interferon (IFN)gamma production by the lymphocytes of peripheral blood and of adenoid tissue, in comparison with children without recurrent otitis. Our study group was represented by 58 children undergoing adenoidectomy for adenoidal hypertrophy. They were subdivided into two groups according to the recurrence of otitis (>or=3 per year) or not (<3 per year). Intracellular cytokine profile of lymphocyte subsets in adenoids and peripheral blood was evaluated by flow cytometry analysis. Children with recurrent otitis showed a significantly lower percentage of CD8+-producing IFN gamma cells in adenoids than children with <3 otitis per year (p = 0.003). The reduced capability of the adenoid cells to produce INF-gamma may induce a high susceptibility to the recurrence of otitis in children.

Low percentages of circulating CD8(+)/CD45RA(+) human T lymphocytes expressing beta7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the alpha4beta7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, alpha4beta7(+) donor T cells. Therefore, we evaluated the correlation existing between circulating beta7(+) T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. PATIENTS AND METHODS: Surface expression of beta7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. RESULTS: We found a significantly higher absolute number of CD8(+) and a significantly lower percentage of CD8(+)CD45RA(+)beta7(+) T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8(+) T cells > or = 60 x 10(6)/L and a percentage of circulating CD8(+)CD45RA(+)beta7(+) T cells < 35%. CONCLUSION: Measuring the absolute number of CD8(+) T cells and percentage of CD8(+)CD45RA(+)beta7(+) T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.

B lymphocyte reconstitution after hematopoietic stem cell transplantation: functional immaturity and slow recovery of memory CD27+ B cells.

OBJECTIVE: Functional recovery of B lymphocytes after hematopoietic stem cell transplantation (HSCT) can take up to 2 years. HSCT recipients may obtain protective titers of pathogen-specific antibody through vaccination, but optimal timing of reimmunization remains to be defined. PATIENTS AND METHODS: In this study, we evaluated the reconstitution of B-cell number and activity in 139 children given HSCT, by B-cell subset phenotyping and in vitro immunoglobulin (Ig) production. RESULTS: Patients were longitudinally studied at 3, 6, 12, and 18 to 24 months after transplantation. At all time points, recipients displayed a significantly higher percentage of naive (IgD+CD27-) B cells and showed significantly lower production of stimulated in vitro Ig as compared to healthy controls. Moreover, during follow-up, we observed an increase in the proportion of patients who had CD27+ B subsets and who were able to mount in vitro Ig production greater than the 5th percentile. CONCLUSION: Similar to what has been described in adults, most children lack memory B cells and produce low amounts of Ig. However, the number of B cells, as well as their function, gradually recovered over time and the spread of data we observed suggests that the reimmunization schedule should be individualized for each patient. It remains to be defined in a prospective clinical study the time point at which a patient should start reimmunization. A reasonable hypothesis to be explored is the time point at which a percentage of memory B cells greater than the 5th percentile of normal controls is reached.

Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot study.

Background. Antipsychotic polypharmacy is used in several psychiatric disorders, despite poor evidence existing to support this practice. Aim. We evaluated whether psychotic patients in acute relapse exposed to antipsychotic polypharmacy (AP + AP) showed different demographic, clinical, or psychopathological features compared to those exposed to one antipsychotic (AP) and whether AP + AP patients showed significantly higher improvement compared to AP patients after a 4-week treatment. Methods. Inpatients were subdivided into AP + AP and AP ones. In the cross-sectional step, patients were compared according to demographics, clinical variables, and scores on rating scales. In the longitudinal step, patients remained for 4 weeks under admission medications and were compared for clinical improvement. Results. AP + AP patients were more frequently diagnosed with schizophrenia and mental retardation as a comorbid illness. AP + AP patients were more frequently under first-generation antipsychotics and had worse clinical presentation. After 4 weeks of treatment, both AP + AP and AP patients improved compared to the baseline. However, AP patients scored significantly less than AP + AP patients at the Clinical Global Impression Scale at the 4-week time point but not at the baseline, indicating a treatment-specific improvement. Conclusions. Antipsychotic polypharmacy may be offered to specific types of psychotic patients. However, efficacy of this strategy is limited at best.

Affective temperaments are associated with specific clusters of symptoms and psychopathology: a cross-sectional study on bipolar disorder inpatients in acute manic, mixed, or depressive relapse.

BACKGROUND: The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder. METHOD: Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data. RESULTS: The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states. LIMITS: Cross-sectional design; sample size. CONCLUSIONS: Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described.

Immune system development in infants born to mothers with autoimmune disease, exposed in utero to immunosuppressive agents.

Exposure to immunosuppressant agents during gestation can affect the fetal immune system. The aim of this study was to evaluate the immune function of infants whose mothers were administered immunosuppressants during pregnancy for the treatment of autoimmune disorders. Circulating lymphocyte subsets and in vitro immunoglobulin production were assessed at birth, and months 1, 6, and 12 of life in 19 infants exposed in utero to glucocorticoid alone or in combination with azathioprine, cyclosporine A, or hydroxychloroquine. The results were compared with those obtained in 15 age-matched infants from mothers with autoimmune diseases not exposed to immunosuppressants. No differences in terms of absolute lymphocyte count, percentage of B and T lymphocytes, and immunoglobulin production were observed. No immune system dysfunction was found in the two studied groups, suggesting a lack of interference between the immunosuppressive treatment and the immune systems of the offspring.

Immunogenicity of a three-component acellular pertussis vaccine administered at birth.

OBJECTIVE: To evaluate within the first 6 months of birth the immunogenicity of a 3-component acellular pertussis (aP) vaccine containing filamentous hemagglutinin (FHA), pertactine (PRN), and genetically detoxified pertussis toxin (PT) in infants who received a dose of vaccine at birth, in addition to the recommended schedule administered at 3, 5, and 11 months. Furthermore, we investigated the influence of maternal antibodies on aP vaccine response. METHODS: We used enzyme-linked immunosorbent assay to evaluate immunoglobulin G antibody levels in 45 infants immunized at birth and at 3, 5, and 11 months (group 1) and in 46 infants immunized at the ages of 3, 5, and 11 months (group 2). All mothers were also tested at delivery. RESULTS: At the age of 5 months the geometric mean titer of anti-PT, anti-FHA, and anti-PRN was significantly greater in group 1 (who had received 2 doses) than in group 2 (1 dose). At 6 months geometric mean titers were significantly higher in group 1 than in group 2 for anti-PRN and anti-FHA, whereas no significant differences were observed for anti-PT. CONCLUSIONS: Immunization at birth may be important for an earlier prevention of the pertussis disease in infants under 6 months, especially in Italy, where the recommended ages for aP vaccine administration are 3, 5, and 11 months.

Human amniotic fluid cells are able to produce IL-6 and IL-8.

PROBLEM: In order to investigate the role of amniotic fluid cells (AFC) in the establishment of feto-maternal immune relationship, we evaluated their phenotype and capacity to produce cytokines. METHODS OF STUDY: CK 7-8, human leukocyte antigen (HLA)-I, HLA-DR, HLA-G, CD1d, CD34, CD45, CD14 surface antigens expression and the intracellular production of IL-4, IL-6, IL-8, IL-10, IL-12, interferon-gamma and tumor necrosis factor-1 were studied in cultured AFC and in eight samples immediately after amniocentesis using flow cytometry. IL-6 and IL-8 were detected by ELISA in all amniotic fluids and in all culture supernatants. Moreover, IL-6 and IL-8 mRNA were tested in nine samples. RESULTS: Cultured AFC express HLA-I, HLA-G and CK 7-8 and are able to produce IL-6 and IL-8, confirmed by presence of their mRNA. We quantified IL-6 and IL-8 levels in all amniotic fluids and in all supernatants. CONCLUSION: Surface antigen expression of AFC are not specific of immune cells, but AFC are able to produce cytokines and we can postulate that they may participate in mechanisms involved in normal as well as pathological pregnancy.