A 12-year-old boy with a large ulcer on the right leg was admitted to our department. The cutaneous ulcer had been unsuccessfully treated for about 6 months with various systemic antibiotics, topical medications, and finally skin graft. His medical history revealed an episode of meningoencephalitis at the age of 6 years. Although he had been diagnosed, on that occasion, with agammaglobulinaemia, he had never received immunoglobulin replacement. On admission, culture of the skin lesion yielded Staphylococcus aureus. Serum concentrations of all classes of immunoglobulin were severely decreased, with IgM being undetectable; peripheral B cells were absent. These laboratory findings are diagnostic for Bruton agammaglobulinaemia. After the first intravenous immunoglobulin administration, the culture became negative and a striking improvement of the ulcer was noticed. Continuous immunoglobulin replacement, every 3 weeks, resulted in complete healing of the leg ulcer in 2 months. After 18 months follow-up, the patient is still on intravenous immunoglobulin administration and is well and free of infections.

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.

OBJECTIVES:we investigated the cause of hypo-responsiveness to vaccines in splenectomized subjects.METHODS:we evaluated the immune responses to a Haemophilus influenzae type b vaccine and the sizes of lymphocyte subpopulations in 25 splenectomized and 45 non-splenectomized thalassaemic patients, in 12 individuals who had been splenectomized after trauma and in 20 controls.RESULTS:the immune response in the controls was significantly higher (P < 0.001) than in splenectomized patients after trauma and in both, the response was higher (P < 0.001) than in thalassaemic patients. In asplenic subjects after trauma, percentages of CD3 and CD4 cells were lower (P < 0.001) than in patients in the other groups; the controls had higher percentages of CD8 cells (P < 0.001) than patients in the other groups. The natural logarithm of the mean percentage of (CD19 showed a quadratic trend from thalassaemic patients through asplenic subjects to controls (P < 0.001). Levels of CD16+ natural killer (NK) cells were higher (P < 0.001) only in asplenic subjects after trauma.CONCLUSIONS:the significant decrease in the immune response of the splenectomized thalassaemic patients vs. non-splenectomized thalassaemic patients may, in part, be due to their basic immunological condition. Thus, the best strategy for protecting these subjects is to vaccinate them before the splenectomy.

A possible role of the immune system in the pathogenesis of some neurologic disorders, including infantile autism, was recently postulated. This observation prompted the authors to investigate some immunologic aspects in a group of patients with Rett syndrome, a disorder still not completely clarified but with some points of commonality with infantile autism. Humoral and cell-mediated immunity were investigated in 20 females with Rett syndrome. Peripheral lymphocyte subsets revealed a reduced percentage of CD8+ suppressor-cytotoxic cells in all of the patients with Rett syndrome, resulting in an increased CD4+/CD8+ ratio. In addition, 15 (75%) of the 20 patients had low levels of natural killer cells. Soluble interleukin-2 receptor was elevated in the youngest patients. Antineuronal and antimyelin ganglioside antibodies were absent, as were antinuclear antibodies, antistriated muscle antibodies, and antismooth muscle antibodies. Immunoglobulin fractions and complement were normal for age in all of the patients.

Purpose: The present study was designed in order to evaluate the extent of alloimmunization against erythrocyte antigens and the presence of autoantibodies in Caucasian patients with sickle cell disease (SCD).Patients and Methods: One hundred and four patients with SCD and 150 normal subjects, matched by age and sex, were studied. Laboratory analyses included blood grouping, screening and identification of antibodies toward erythrocyte antigens, serum autoantibodies (antinuclear, ANA; anti-smooth muscle, ASMA; anti-mitochondrial, AMA; anti-double stranded DNA).Results: Alloimmunization against erythrocyte antigens was present in 5.1% of transfused patients and autoantibodies were present in 12.5% of patients.Conclusions: The extent of the alterations found in our Caucasian patients was lower than the one reported in other studies carried out on patients of African descent.

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.

We prospectively determined serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) in the first 2 weeks of life in 32 preterm newborns in an attempt to assess whether these concentrations are reliable markers of sepsis in newborns at risk of infection. Ten of the study group were normal and had been hospitalized only for low birth weight. The remaining 22 presented respiratory distress (RDS) and were at even higher risk of infection because they required assisted mechanical ventilation and central venous catheterisation for parenteral feeding and infusion therapy. Sepsis was diagnosed in 11/22 newborns with RDS: in 3 on day 3 and in 8 on day 7. Circulating sICAM-1 concentrations were significantly elevated in neonates with RDS (group II) and associated infection (group III) compared with normal newborns (group I). However, after day 3 of life sICAM-1 values were significantly higher in group III than in group II.

Some data suggest that cesarean section reduces mother-to-child HIV-1 transmission. To assess the influence of mode of delivery and other maternal and infant factors on the rate of transmission, we analyzed the data of 1,624 children prospectively followed from birth. Of these, at the last visit 1,033 were > 18 months of age or would have been had they not died of HIV-related illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1-23.5) second-born children. Multivariate stepwise analysis showed that vaginal delivery and development of symptoms in the mother were significantly and independently associated with a higher transmission rate (vaginal delivery: odds ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3), In contrast, a history of maternal drug use, birth weight, breastfeeding (only 37 infants were breast-fed), and child's sex did not have a significant impact on viral transmission. The percentage of infected children was highest (30.7%) among very premature infants (less than or equal to 32 weeks of gestation); this significant trend subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel reduction in peripartum transmission. The reduced rate of infection observed in infants born by cesarean section underlines the urgent need for randomized controlled trials to evaluate the protective role of surgical delivery in preventing perinatal HIV-1 transmission.

Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms.

Summary. α‐interferon (α‐IFN) has been used to treat chronic non‐A non‐B hepatitis in thalassaemic patients with response rates from 45% to 83%. Unfortunately, treatment with α‐IFN is associated with side‐effects which have a negative effect on the quality of life of the patient. Therefore it would be useful if we could distinguish in advance those patients who would benefit from such therapy from those who would not. In the present study we found that the modification of lymphocyte subsets 20 h after the administration of the first dose of α‐IFN revealed that relative numbers of T helper lymphocytes (CD4 + ) increased in three non‐responding patients and decreased in five responding patients, whereas those of T suppressor lymphocytes (CD8 + ), and natural killer cells (CD57 + . CD16 + ) decreased in non‐responding patients and increased in responding patients. Therefore analysis of the lymphocyte subsets CD4, CD8, CD57 and CD16 before and 20 h after the administration of α‐IFN can be used to predict the clinical response to treatment with α‐IFN.

As of April 1992, 2337 children born to HIV-1-positive mothers were recorded by our multicentre study. Another 131 children were infected by contaminated blood products, while in 5 cases the risk factor remained unknown, as their personal history was lacking. The number of perinatally exposed children increased exponentially from 1981 to 1986, then stabilized. Of these, at last visit 624 were infected (531 P-2, 93 P-1), 463 were P-O and 1195 had seroreverted. Drug addiction continues to be the most frequent maternal risk factor, although infection acquired through sexual contact gradually increased up to 26.5% in 1991. Of the 762 first children identified at birth and older than 15 months of age, 132 (17.3%) acquired infection and seroconverted to HIV. A similar transmission rate was observed in 43 second-born children.

Article Does Endogenous Growth Hormone Influence Immune Function? Immunological Studies in Laron's Dwarfism was published on January 1, 1991 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 4, issue 1).

The Italian Register for HIV-1 infection in children was instituted in 1985 by the Italian Association of Pediatrics. As of March 1990, 1422 children (1321 born to seropositive mothers, 99 infected by blood products and 2 whose personal history was not available) were enrolled in our multicentre study. The number of perinatally exposed children was higher in industrialized areas and has been increasing over the years. Intravenous drug use (66.4%), sexual contacts with infected partner (14.5%) or both (15.6%) were the main mother's risk factors, with increasing proportion of those infected by sexual contacts (up to 21% in 1989). The mother-to-offspring transmission rate was 19.9%, when assessed in first born children prospectively followed-up from birth who remained seropositive after 18 months of age.Efficiency of infection was higher in children born to symptomatic mothers, whereas it was unaffected by mode of delivery, gestational age or birthweight. The role of breast-feeding remains doubtful. The risk of infection was not increased at second pregnancy (33 siblings studied) and infection status was disconcordant only in 1/10 twin pairs. Perinatally exposed population consisted of 396 infants whose infection status was still indeterminate (P-0), 388 infected children (93 P-1), including 31 antibody-negative, viral marker-positive subjects, and 295 P-2) and 537 uninfected children. 82.6% of infected seropositive children developed HIV-related clinical manifestations at a median age of 4 months. 69 (23.4%) P-2 patients have died at a median age of 12 months. Decreased CD4 + lymphocyte counts and increased serum immunoglobulin levels in the first months of life were indexes of disease progression rather than of infection status. Specific secondary infections, neurologic disorders, growth failure, fever, anemia and hepatitis were significantly and independently correlated to a poor prognosis. 688 doses of diphteria-tetanus vaccine, 476 of inactivated polyomielitis and 327 of attenuated live polyomielitis vaccine were administered in infected infants with no recorded side effects. Among bloodborne HIV-1 infections (48 haemophilics, 41 beta-thalassemics and 10 occasionally transfused children), only anecdotal cases have been recorded after 1985, when specific preventive measures were adopted. Clinical evolution was worse in perinatally infected children when compared to that of those who acquired infection through administration of blood products.HIV-1 infection in childhood has become a main problem in Italy. Diffusion by blood products has been widely restrained, but the increasing number of perinatally infected children indicates that further specific efforts and strategies in the field of public health are needed.

We examined lymphocyte subsets in peripheral blood from children with visceral leishmaniasis both in the active stage of the disease and after recovery. At diagnosis, CD2+ and CD4+ cells showed a significant decrease while CD8+ cells were significantly increased when compared with controls; CD4/CD8 ratio was inverted. All of these alterations returned to normal values 3 months after recovery.