No abstract

Sixty patients (16 children, 44 adults) participated in the study aiming at evaluating: (i) IgG levels when switching patients from intravenous IgG (IVIG) infusions in hospital to subcutaneous (SCIG) self-infusions at home using the same cumulative monthly dose, (ii) protections against infections, and (iii) safety of a new, ready-to-use 16% IgG preparation. All children and 33 adults had received IVIG therapy for >6 months at enrolment. Ten adults who had been on SCIG therapy for many years served as controls. Mean serum IgG trough levels increased in the pre-IVIG children from 7.8 to 9.2 g/L (non-inferiority: p < 0.001) and in the adults from 8.6 to 8.9 g/L (non-inferiority: p < 0.001). Totally 114 respiratory tract infections occurred, 90% of them mild. One serious bacterial infection (pneumonia) was reported for one adult. The annualized rate of serious infections was 0.04 episodes/patient. In total 2297 infusions were given and 28 (1%) systemic adverse reactions occurred, none of them severe. Local tissue reactions declined over time, this being particularly distinct after 8 to 10 weeks. In conclusion, the SCIG administration route was safe. High IgG levels were easily maintained resulting in a very good protection against infections.

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute significantly to the neurological damage commonly associated with this serious disease. In this study we tested whether or not inhibition of leukocyte rolling, a precondition for firm leukocyte adhesion to vascular endothelium in vivo, may reduce CSF leukocyte recruitment and associated inflammatory changes in rabbits with experimental meningitis. As documented by intravital microscopy of small venules in the rabbit mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer of sulfated L-fucose known to block the function of the leukocytic "rolling receptor" L-selectin. Moreover, fucoidin treatment dramatically reduced the accumulation of both leukocytes and plasma protein in the CSF of rabbits challenged intrathecally with pneumococcal antigen. These main findings thus illustrate that inhibition of leukocyte rolling, an early and obligatory step in the process of leukocyte extravasation, may be an effective therapeutic approach to attenuate leukocyte-dependent central nervous system damage in bacterial meningitis. (J. Clin. Invest. 1994. 93:929-936.)

350 adult patients in Sweden were included in a retrospective study covering more than 2000 patient-y, to evaluate the efficacy of immunoglobulin (Ig) prophylaxis. All patients had selective or combined IgG subclass deficiency, without IgA deficiency, and suffered from recurrent respiratory tract infections (RTIs). The patients had been given Ig prophylaxis for 0.5-21 y (mean 5.5 y). In total, 164/350 of the patients had a concomitant lung disease. Because of the heterogeneity of this retrospective material we evaluated only those patients with 4 or more antibiotic-demanding (i.e. presumably bacterial) episodes of RTI per y treated with an Ig dose of about 100 mg/kg/week (132/350). The frequency of antibiotic treated RTIs prior to and during latest y/s of Ig prophylaxis was compared. No difference in response could be found between patients with and without chronic lung diseases. In 92/132 a > or = 50% reduction of the rate of episodes of antibiotic-demanding RTIs was recorded (p < 0.001). The overall reduction of the RTI frequency was for IgG1 57%, IgG2 59%, IgG3 63% and for the combinations 61% (all p<0.001).

Phosphoglucomutase 3 (PGM3) is an enzyme converting N-acetyl-glucosamine-6-phosphate to N-acetyl-glucosamine-1-phosphate, a precursor important for glycosylation. Mutations in the PGM3 gene have recently been identified as the cause of novel primary immunodeficiency with a hyper-IgE like syndrome. Here we report the occurrence of a homozygous mutation in the PGM3 gene in a family with immunodeficient children, described already in 1976. DNA from two of the immunodeficient siblings was sequenced and shown to encode the same homozygous missense mutation, causing a destabilized protein with reduced enzymatic capacity. Affected individuals were highly prone to infections, but lack the developmental defects in the nervous and skeletal systems, reported in other families. Moreover, normal IgE levels were found. Thus, belonging to the expanding group of congenital glycosylation defects, PGM3 deficiency is characterized by immunodeficiency, with or without increased IgE levels, and with variable forms of developmental defects affecting other organ systems.