Casper Jersild

HISTOCOMPATIBILITY DETERMINANTS IN MULTIPLE SCLEROSIS, WITH SPECIAL REFERENCE TO CLINICAL COURSE

Abstract Twenty-eight randomly selected patients with multiple sclerosis (M.S.) were typed in the mixed-lymphocyte culture test for a specific lymphocyte determinant LD-7a by means of LD-7a homozygous stimulator cells. Nineteen (70%) of the patients were LD-7a positive, a frequency much higher than the 16% observed in healthy individuals. Thirteen of the patients carried HL-A7, and all of these were LD-7a positive, which is significantly different (p=0·004) from the frequency of about 56% of this determinant in twenty-five normal HL-A7 positive individuals. Of the remaining fifteen patients, six carried LD-7a, which is also a significantly higher frequency (p=0·009) than that observed in normal HL-A7 negatives (three in forty individuals). Family studies showed that the LD-7a character is inherited and not acquired. The progression of the disease was significantly (P

Reconstitution in Severe Combined Immunodeficiency by Transplantation of Marrow from an Unrelated Donor

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.

Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis.

The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.

The effect of n-3 fatty acids on neutrophil chemiluminescence

The effect of dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) on the production of free oxygen radicals from activated neutrophils was investigated in healthy subjects, using chemiluminescence. In the first study 22 persons were give 4 g n-3 PUFAs daily for 6 weeks. There was a median reduction of chemiluminescence from neutrophils stimulated with opsonized zymosan of 37% (p < 0.001). The median content of eicosapentaenoic acid in platelets, used as an indicator for cellular fatty acid profile, increased from 0.70 to 2.80% (p < 0.001), and there was a significant negative correlation between the chemiluminescence signal and the content of eicosapentaenoic acid in platelets (p < 0.001). In a second, low-dose study 24 persons were allocated to daily supplementation with either 0.65 g n-3 PUFAs or with a control oil for 6 weeks. Compared to the control group there was a median reduction of 38 and 44% in chemiluminescence from neutrophils stimulated with opsonized zymosan and phorbol,12-myristate,13-acetate (PMA), respectively. Neither of these differences, however, was statistically significant. These findings lend support for a possible role of n-3 PUFAs in the management of inflammatory disorders.

n-3 fatty acids and leukocyte chemotaxis. Effects in hyperlipidemia and dose-response studies in healthy men.

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to inhibit neutrophil and monocyte chemotaxis in healthy subjects and, with respect to neutrophils, also in various patient groups. We studied the effect of dietary supplementation with n-3 PUFAs on monocyte and neutrophil chemotaxis in patients with hyperlipidemia. Chemotaxis was investigated with the under-agarose assay, using autologous serum and N-formyl-methionyl-leucyl-phenylalanine as chemoattractants. The patients were examined before and after 6 weeks of supplementation with 6 g n-3 PUFAs daily. Monocyte chemotaxis was reduced after n-3 PUFA supplementation in type IIa patients but was unaffected in patients with type IV hyperlipidemia. Furthermore, monocyte chemotaxis was increased in untreated type IIa patients compared with normocholesterolemic controls. We also studied the dose-response effects of n-3 PUFAs on monocyte and neutrophil chemotaxis in healthy men given 1.3, 4, and 9 g n-3 PUFAs daily for 6-week periods. Monocyte and neutrophil chemotaxis was reduced after n-3 PUFA supplements in a dose-dependent fashion, with the majority of the effect observed after the low dose. These results lend support to the notion of an antiatherosclerotic effect of n-3 PUFAs and may provide an explanation for the hitherto-unexplained effect of low doses of n-3 PUFAs in coronary heart disease.

FcγRIIIB polymorphism: evidence that NA1/NA2 and SH are located in two closely linked loci and that the SH allele is linked to the NA1 allele in the Danish population

BACKGROUND: The neutrophil‐specific antigens NA1, NA2, and SH are well‐recognized allotypic forms of FcγRIIIB. Individuals carrying all three FcγRIIIB genes were recently described.

Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study

BACKGROUND Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion. METHODS We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors. FINDINGS Of the 354 094 transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors. INTERPRETATION Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.

A population-based binational register for monitoring long-term outcome and possible disease concordance among blood donors and recipients

Background and Objectives  Even with appropriate donor deferrals and advanced screening tests, the risk of disease transmission through blood transfusion cannot be completely disregarded. Efficient monitoring of possible disease transmission between blood donors and recipients should be an important component of a comprehensive haemovigilance system.

The effect of n-3 polyunsaturated fatty acids on lipids, haemostasis, neutrophil and monocyte chemotaxis in insulin-dependent diabetes mellitus

Abstract. Insulin‐dependent diabetes mellitus (IDDM) is associated with an increased risk of coronary artery disease (CAD). There is some evidence that polyunsaturated fatty acids of the marine n‐3 type (n‐3 PUFAs) may offer protection against CAD. We have studied the effect of short‐term dietary supplementation with n‐3 PUFAs on lipids, haemostasis, neutrophil and monocyte chemotaxis in 10 patients with IDDM. The patients were given 4 g daily of n‐3 PUFAs (fish oil) for 6 weeks and were investigated before and after the supplement. No significant effects on platelets or haemostasis were observed. High density lipoprotein (HDL)‐cholesterol significantly increased, and triglycerides and the ratio of total cholesterol to HDL‐cholesterol significantly decreased. Monocyte chemotaxis was unaltered, while neutrophil chemotaxis significantly increased after fish oil. The finding of an improvement in neutrophil chemotaxis after supplementation with n‐3 PUFAs to patients with IDDM needs to be confirmed in future studies.

The Effect of Previous Blood Transfusion on Lymphocyte Subsets and Natural Killer Cell Function in Patients with Colorectal Cancer

To elucidate the possible influence of previous blood transfusion on immune functions, the transfusion history of 153 patients admitted to hospital for elective colorectal surgery was correlated with lymphocyte subsets and natural killer (NK) cell function. The subsets determined were CD2, CD3, CD4, CD8, CD16, CD20, CD56, CD57 and HLA‐DR‐positive. The NK cell function was determined by measuring the killing capacity against cFDA‐labelled K562 target cells monitored via a flow‐cytometer. We found that 42 patients (27%) had been transfused before surgery, of these 13 had been transfused less than 30 days before surgery and 29 (19%) transfused more than 30 days before (median 10 years, range 0.1–37 years). In transfused patients, we found a significantly reduced number of B lymphocytes (CD20; p = 0.01), a reduction in HLA‐DR‐positive cells (p = 0.02) and a just significant reduction of NK cell function in transfused compared to nontransfused patients. The reduction in NK cell function is marginal and the NK cell function is within normal range, and probably without clinical significance. Reduction in NK cell function has been described before, whereas the reduction in B cells has not been reported earlier. The results may suggest an impaired humoral immunity and a minor reduction in cellular immunity in patients following blood transfusion.