Huddinge University Hospital is a major teaching hospital affiliated with the Karolinska Institute in Southern Stockholm. For the past few years several groups have been working there in different areas of gene therapy relating to cancer, genetic and infectious diseases. However, a facility to produce clinical grade material under good manufacturing practice was lacking. To this end, Huddinge University Hospital has taken the initiative to open a Gene Therapy Research Center in 1996. This facility, which is unique of its kind in Scandinavia, is located in the Novum Research Park, Huddinge, and is a part of the existing Clinical Research Center. The newly built centre will allow clinicians and researchers to develop and produce vectors (viral and nonviral) for clinical trials and do basic research to understand the mechanisms of diseases. Although the centre will primarily serve the academic institutions it will also extend its facilities to other investigators in this field. The production unit is run in collaboration with the Faculty of Medicine, University of Lund. On-going projects include production of plasmid vectors for prevention of postangioplasty restenosis, DNA vaccine for HIV-1, cationic liposome DNA complexes for cystic fibrosis and retroviral vectors for HIV-1.
Gm phenotype frequencies were examined in 112 Swedish myasthenia gravis patients. The G1m 1,2,3 phenotype frequency in the total patient material did not differ significantly from that found in the normal population. However, when patients were subdivided, three different patient groups were observed with regard to Gm1 frequency: (1) Thymoma patients having a low frequency of Gm1, (2) Non-thymoma patients with a mild disease having a low frequency of Gm1 and (3) Non-thymoma patients with a severe disease having a high frequency of Gm1. When patients were subdivided according to presence or absence of HLA-B8 and Gm1 respectively, severe symptoms were less frequent in the HLA-B8+, Gm(-1) group as compared to the HLA-B8+, Gm(+1) group. Furthermore, there was an increased frequency of sera with anti-immunoglobulins not inhibitable by pooled control immunoglobulins.
To estimate the prevalence of chronic granulomatous disease (CGD) in Sweden, an inquiry asking for known and possible CGD cases was mailed to paediatric, internal medicine and infectious disease departments all over Sweden. The detected patients were characterized as to genetics and the clinical presentation. Twenty-one patients (belonging to 16 different families) were found, corresponding to a prevalence of approximately 1/450,000 individuals. The patients with X-linked disease, lacking a functional gp91phox protein (n = 12), comprised 57% and 43% of the patients had an autosomal recessive (AR) disease lacking p47phox (n = 7) or p67phox (n = 1), respectively. All unrelated patients with X-linked disease displayed different gene abnormalities such as point mutations predicting nonsense (n = 3), missense (n = 1) or splice site mutations (n = 2), but also a total deletion and a unique 40 base pair duplicature insertion. The patients with p47phox-deficiency showed a GT deletion at a GTGT tandem repeat, and the p67phox-deficient patient displayed a heterozygous in-frame deletion of AAG combined with a large deletion in the other allele. Three patients died during the study period, two from pseudomonas cepacia infections. Patients with X-linked disease had more frequent infections (mean of 1.7 per year), than the patients with AR inheritance (0.5 infections per year). The most common infections were dermal abscesses (n = 111), followed by lymphadenitis (n = 82) and pneumonias (n = 73). Inflammatory bowel disease-like symptoms, mimicking Crohn's disease of the colon, was seen in three CGD patients.
