Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency.
To evaluate the presence of immunodeficiency in a series of 6 patients with JS.
Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry.
Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found.
Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia characterised by short limbed short stature, hypoplastic hair growth, and impaired cell mediated immunity and erythrocyte production. The syndrome is exceptionally prevalent among the Finns and among the Old Order Amish in the United States; sporadic cases have been reported from other countries. An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years. The incidence was estimated to be 1:23,000 live births. Consanguinity was found in two families and interfamilial relationships in 20 families. Geographical distribution of the birth places of the patients and their great grandparents showed accumulation in a small area in western Finland and regional clusters were seen in other parts of the country as well. The result of the segregation analysis was in accordance with recessive inheritance with reduced penetrance.
The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Program (NVP) in September 2010 with a 2+1 schedule (3, 5, 12 months) without catch-up vaccinations. We evaluated the direct and indirect effects of PCV10 on invasive pneumococcal disease (IPD) among children =5 years of age during the first three years after NVP introduction.
We conducted a population-based, observational follow-up study. The cohort of vaccine-eligible children (all children born June 1, 2010 or later) was followed from 3 months of age until the end of 2013. For the indirect effect, another cohort of older children ineligible for PCV10 vaccination was followed from 2011 through 2013. Both cohorts were compared with season- and age-matched reference cohorts before NVP introduction. National, population-based laboratory surveillance data were used to compare culture-confirmed serotype-specific IPD rates in the vaccine target and reference cohorts by using Poisson regression models.
The overall IPD rate among vaccine-eligible children was reduced by 80% (95%CI 72 to 85); the reduction in vaccine-type IPD was 92% (95%CI 86 to 95). However, a non-significant increase in non-vaccine type IPD was observed. During 2012-2013, we also observed a 48% (95%CI 18 to 69) reduction in IPD among unvaccinated children 2 to 5 years of age, which was mostly attributable to the ten vaccine serotypes.
This is the first population-based study investigating the impact of PCV10 introduction without prior PCV7 use. A substantial decrease in IPD rates among vaccine-eligible children was observed. A smaller and temporally delayed reduction among older, unvaccinated children suggests that PCV10 also provides indirect protection against vaccine-type IPD. Changes in serotype distribution warrant continuous monitoring of potential increases in non-vaccine serotypes.
Previous reports have suggested an increased risk of cancer among patients with cartilage-hair hypoplasia (CHH). This study was carried out to further evaluate this risk among patients with CHH and their first-degree relatives.
One hundred twenty-two patients with CHH were identified through 2 countrywide epidemiologic surveys in 1974 and in 1986. Their parents and nonaffected siblings were identified through the Population Register Center. This cohort underwent follow-up for cancer incidence through the Finnish Cancer Registry to the end of 1995.
A statistically significant excess risk of cancer was seen among the patients with CHH (standardized incidence ratio 6.9, 95% confidence interval 2.3 to 16), which was mainly attributable to non-Hodgkin's lymphoma (standardized incidence ratio 90, 95% confidence interval 18 to 264). In addition, a significant excess risk of basal cell carcinoma was seen (standardized incidence ratio 35, 95% confidence interval 7.2 to 102). The cancer incidence among the siblings or the parents did not differ from the average cancer incidence in the Finnish population.
This study confirms an increased risk of cancer, especially non-Hodgkin's lymphoma, probably attributable to defective immunity, among patients with CHH.
Retrospective studies suggest that there is an increased postoperative morbidity among alcohol misusers. We have prospectively studied the risk of alcohol intake among patients undergoing surgery. We investigated 15 symptom-free subjects who required colorectal surgery and who were drinking at least 60 g of alcohol per day. These patients were matched for sex, nutrition, age, weight, cardiovascular and pulmonary disease, diagnosis, anaesthesia, and surgery to 15 control subjects who were consuming below 25 g of alcohol daily. Those drinking at least 60 g of alcohol per day developed more postoperative complications than controls (67% vs 20%, p less than 0.05) and hospital stay was prolonged (20 vs 12 days, p less than 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection fraction (median, 54% vs 68%, p less than 0.01). Delayed hypersensitivity responses were smaller in the alcohol group before (53 mm2 vs 78 mm2, p less than 0.05) and after (18 mm2 vs 55 mm2, p less than 0.01) surgery. Alcohol misusers had longer bleeding times during the first postoperative week (p less than 0.01). Surgical stress responses, as assessed by changes in plasma cortisol and catecholamines, were higher among alcoholics (p less than 0.05). Postoperative morbidity is increased in symptom-free alcohol misusers. The mechanism is probably subclinical cardiac insufficiency, immunosuppression, and decreased haemostatic function. Preoperative alcohol consumption may be a more important risk factor than previously thought.
A nationwide survey of symptomatic primary immunodeficiency disorders in children in Sweden during the 6-year period 1974-1979 resulted in 201 reported cases. The reported data for 174 children were analyzed. Antibody deficiencies were the most frequent (45.0%), followed by phagocytic disorders (22.0%) and combined T- and B-cell disorders (20.8%). Thirty-two children (18.4%) died, with the highest mortality for combined T- and B-cell defects. The sex ratio for all disorders was 2:1 for boys:girls. Neutropenia was significantly more common in the northern part of Sweden.
The levels of trace elements in the biological substrates were comparatively analyzed in the children living in the towns of Aktobe, Orenburg, and Orsk. The values of blood metals were ascertained in the Aktobe children residing in the areas differently spaced from the town's industrial zone. Immunity was evaluated and the degree of immunodeficiency was established.
The present paper analyzes immunological parameters and the incidence of secondary immunodeficiency (SID) in physicians and medium-levelled medical staff contacting with tuberculous and non-specific infection. Suppressed cell immunity was recorded in 44% of the medical staff of a pulmonary surgical tuberculosis hospital, with increased length of service there was a rise in the number of patients diagnosed as having immunodepression. The clinical manifestations of SID were recorded in 56% in this group and they were most pronounced in a group of long-working personnel. The proportion of persons with immunodepression proved to be twice higher among nurses than among physicians. Nurses are at the highest risk for immunopathological states. This common occurrence of SID among medical staff is an indicator to make an obligatory regular immunological examinations of the staff for the prevention and immunotherapy of SID.