Background: There is currently no international reference preparation for IgG subclass (IgGSc) quantification. This situation has led to calibration differences among assays and a variety of reference interval values with consequential difficulties in comparing results. We therefore evaluated IgGSc concentrations in Certified Reference Material 470 (CRM 470). Methods: Pure, polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as primary standards. The IgG mass in each preparation was calculated from amino-acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry with modern analytical techniques, using these reference preparations. Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250 males and 130 females), and age-dependent reference intervals were established.
Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and for tetanus toxoid were measured in serum samples of 386 age-stratified subjects. The study group consists of healthy adult blood donors and hospitalized children undergoing elective surgery, excluding individuals with a history of infection. In children, anti-tetanus toxoid antibody levels displayed two peaks of 1.20 IU/ml (20.4 mg/liter) and 1.65 IU/ml (28.1 mg/liter) related to the schedule of routine childhood immunization in the first year and at 8 years of age. Eighty percent of the antibodies are of the immunoglobulin G1 (IgG1) isotype. For pneumococcal capsular polysaccharide (PCP), the specific antibody levels represent the acquisition of natural immunity. The initial concentration of 9.2 mg/liter was low in infancy (0.5 to 1 years of age) and remained low until 3 to 4 years of age (14.6 mg/liter). During this period PCP antibodies were almost 100% of the IgG2 subclass. Thereafter, IgG anti-PCP antibody titers increased steadily to adult levels (59.5 mg/liter). The data are intended to provide reference ranges to aid in the interpretation of specific antibody determinations in the clinical setting.Serum-specific antibody levels are widely used as indicators of immune competence (25,31). Interpretation of the results may be difficult. Although patients with congenital immunodeficiencies, such as common variable immunodeficiency (1, 7), selective immunoglobulin G (IgG) subclass deficiency (2, 8), and selective antibody deficiency with normal immunoglobulins (2), often have low levels of serum antibodies, many subjects with normal immune function also have low levels of serum-specific antibodies. A physiological delay of the immune response, especially to polysaccharide capsular antigens, a lack of immunization and, in addition, a decrease in specific antibody titers with time (11, 18) determine the outcome of serumspecific antibody measurements. Furthermore, in recent years the routine vaccination schedule has changed. In particular, Haemophilus influenzae type b (Hib) conjugate was introduced (36). Moreover, routine enzyme-linked immunosorbent assay (ELISA) test kits became available that allow specific antibodies to be assigned to IgG subclasses. The present study was designed to establish the pattern of specific antibody responses to polysaccharide and protein antigens in a large cohort of healthy subjects from Germany. MATERIALS AND METHODSSubjects. The subjects of the present study were 313 clinically healthy children (214 males and 99 females) from 6 months to 18 years of age who were admitted to the hospital for minor surgery. Informed consent was obtained from the parents. The adult subjects were 73 healthy blood donors (36 males and 37 females) ranging from 20 to 61 years of age. Only subjects who were free of recurrent infections or inflammation, as assessed by a standardized questionnaire, and whose C-reactive protein concentrations were within the normal limit were incl...
Long term cultures of human bone marrow cells on poly(L-lactide-co-D,L-lactide) 70:30 and 90:10 plates were observed by means of scanning electron microscopy (SEM), SEM-EDX (SEM combined with energy dispersive X-ray analysis), flow cytometry, histochemical stainings, and culture medium analysis. After 14 days culture, cell numbers were only slightly lower compared with our reference material, hydroxyapatite, and much higher compared with polyethylene. There was evidence of collagenous matrix production with osteoblast activity. Acridine orange stainings as well as flow cytometry after incubation with propidium iodide showed only a few non-viable cells. By means of flow cytometry, we found about 30% of cells with granulocyte-markers, some monocyte-derived cells, and only small amounts of lymphocytes. After 9 weeks culture, there was evidence of calcium-phosphate deposition with extracellular matrix. There were only slight differences between the two tested polymers. Our culture system with human bone marrow cells plated on two bioresorbable polymers suggests a biocompatibility almost as good as hydroxyapatite, which is usually well tolerated. There was even evidence of mineralized collagenous matrix after some weeks of culture, which was detected earlier than the mineralization of cell-free controls.
The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae—mainly cardiovascular—were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.
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