5.2, 95% confidence interval 2.2-10.3). In addition, a significantly increased RR was found for cancer of the lung (RR 1.9; n = 15)' the liver (RR 8.0; n = 5)' and the vagina/vulva (RR 5.7; n = 3).Conclusion. There seemed to be a positive association between SLE and non-Hodgkin's lymphoma.Other cancers with a possible virus-related etiology, such as liver and vaginalhlva cancer, were also observed in excess. In addition, there was an indication of an increased risk of lung cancer among patients who were hospitalized for SLE.Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology, with a prevalence in Scandinavia of 1 in 2,800 persons (1). The disease is much more common among

SUMMARYThe extremely high risk reported for some types of cancer among patients with common variable immunodeficiency (CVID) is based on a limited number of investigations. Therefore, we examined the risks for cancer among 562 Danish and Swedish patients with CVID or IgA deficiency and 2071 relatives in 1958-96. The patients were identified through an Immunodeficiency Register and hospital records, while the relatives were traced through population registers. Cancer incidence was assessed by linkage to the Cancer Registries and compared with that in the general population. Among 386 patients with IgA deficiency, the incidence of cancer was not increased (standardized incidence ratio (SI) = 1·0); but two cases of stomach cancer were found, resulting in a non-significant increase in risk (SIR = 5·4; 95% CI = 0·7-19·5). Among 176 patients with common variable immunodeficiency (CVID), the incidence of cancer at all sites combined was increased (SIR = 1·8; 95% CI = 1·0-2·9), which was due mainly to significant excesses of malignant lymphoma (obs = 4; SIR = 12·1; 95% CI = 3·3-31·0) and of stomach cancer (obs = 3; SIR = 10·3; 95% CI = 2·1-30·2). Among the 626 relatives of patients with CVID, no increase in risk was found for these types of cancer or for cancer overall (obs = 53; SIR = 1·0; 95% CI = 0·8-1·3). Our data show that the risks for malignant lymphoma and stomach cancer among patients with CVID may be lower than reported previously. The absence of an increased risk among relatives suggests that the increased cancer morbidity in patients with CVID is related to the immunodeficiency per se rather than to specific genetic traits shared with their relatives.

Homozygosity for MBL variant alleles was observed in 7.7% of the SLE patients compared with 2.8% of the controls (P = 0.06), while no difference was seen for heterozygosity (33.0% versus 34.4%). Homozygotes had an increased risk of acquiring serious infections compared with patients who were heterozygous or homozygous for the normal allele (odds ratio 8.6, 95% confidence interval 1.5-47.6, P = 0.01). The time interval from the diagnosis of SLE to the first infectious event was shorter (P = 0.017), and the annual number of infectious events was 4 times higher, among homozygotes (P = 0.00002). They were especially prone to acquire pneumonia (P = 0.00004). CONCLUSION; Homozygosity for MBL variant alleles may explain much of the increased risk of complicating infections seen in SLE patients. Additionally, it is a minor risk factor for acquiring SLE.

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.

We conclude that this theoretically based model for classification of disease manifestations in PSS contains descriptive and analytic powers which may assist the clinical handling of these patients.

The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.

Reduced levels of somatic hypermutation (SHM) have recently been described in IgG-switched immunoglobulin genes in a minority of patients with common variable immunodeficiency (CVID), demonstrating a disruption of the normal linkage between isotype switch and SHM. To see if, irrespective of isotype, there is a tendency to use unmutated immunoglobulin genes in CVID, we studied SHM in light-chain transcripts using a V A27-specific restriction enzyme-based hot-spot mutation assay (IgREHMA). Hot-spot mutations were found in 48% (median; reference interval, 28%-62%) of transcripts from 53 healthy controls. Values were significantly lower in 31 patients (median, 7.5%; range, 0%-73%; P < .0000001) of whom 24 (77%) had levels below the reference interval. Low levels of SHM correlated with increased frequency of severe respiratory tract infection (SRTI; P < .005), but not with diarrhea (P ‫؍‬ .8). Mannose-binding lectin (MBL) deficiency also correlated with SRTI score (P ‫؍‬ .009). However, the correlation of SHM and SRTI was also seen when only patients with normal MBL genotypes were analyzed (n ‫؍‬ 18, P ‫؍‬ .006). A slight decline of mutated fractions over years was noted (P ‫؍‬ .01). This suggests that most patients with CVID fail to recruit affinity-maturated B cells, adding a qualitative deficiency to the quantitative deficiency characterizing these patients. (Blood. 2005;105:511-517)

MBL levels have no discernible influence on the occurrence or course of infections in AML patients during the initial hospitalisation. The predominant immunodeficiency during this phase is the profound granulocytopenia, which also compromises important effector functions of MBL. The finding in most AML patients of elevated MBL concentrations on admission is most likely because of the role of MBL as an acute phase reactant.