Monocyte function in IDDM patients and healthy individuals.

Interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) may be pathogenetically important in insulin-dependent diabetes mellitus (IDDM), which is associated with genes of the HLA region. Since a regulatory role of HLA region genes on monokine production may exist, we looked for an association between the monokine and prostaglandin E2 (PGE2) responses of monocytes (Mo) from 20 healthy males (18-50 years) with HLA-DR types relevant for IDDM susceptibility and resistance (DR1,2, DR1,3, DR1,4, DR3,4). Monokine assays were established and evaluated and the secretions of IL-1 beta, TNF-alpha, and PGE2 measured in Mo cultures (2h, 6h, 20h) prepared by endotoxin-free techniques and stimulated by low-dose E. coli lipopolysaccharides (LPS). There were no significant associations between Mo responses and HLA-DR phenotype. Likewise, Mo from DR2 (n = 5) and DR4 (n = 5) homozygous healthy males demonstrated no significant differences in monokine and PGE2 responses of Mo. In the HLA class III region a diallelic TNF-beta gene NcoI polymorphism consisting of alleles of 5.5 kb and 10.5 kb was recently described and associated with susceptibility to autoimmune diseases including IDDM. We report that IL-1 beta and TNF-alpha responses of Mo from TNF-beta 10.5 kb homozygous healthy individuals were significantly higher than for TNF-beta 5.5/10.5 kb heterozygotes. IL-1 beta and TNF-alpha responses of Mo from males (18-35 years) with newly diagnosed (n = 10) and long-standing IDDM (n = 10) and from age- and HLA-DR-matched healthy males (n = 10) were studied. LPS, gamma interferon (IFN), and TNF-alpha-stimulated Mo cultures were investigated. No significant differences were found between Mo responses of IDDM patients and controls. IFN (1000 U/ml) in the presence of LPS significantly potentiated LPS-stimulated Mo TNF-alpha secretion and reduced the levels of IL-1 beta immunoreactivity in Mo lysates. IFN and TNF-alpha did not have any effects on LPS-stimulated Mo secretion of IL-1 beta immunoreactivity. We conclude that Mo IL-1 beta and TNF-alpha production is normal in patients with recent-onset and long-standing IDDM. The interindividual differences in monokine responses may be accounted for by the diallelic human TNF-beta gene polymorphism rather than by HLA class II genes. This observation may be important for understanding the association of certain HLA haplotypes with autoimmune phenomena and disease.

Lewis blood type frequency in patients with primary Sjögren's syndrome. A prospective study including analyses for A1A2BO, Secretor, MNSs, P, Duffy, Kell, Lutheran and rhesus blood groups.

Seventy-five patients in two randomly selected groups (N = 40 plus 35) with primary Sjögren's syndrome were tested for Lewis, A1A2BO, secretor, MNSs, P, Duffy, Kell, Lutheran and rhesus blood group antigens. The results were compared with the frequencies in a control group and in the general population. The Lewis blood group frequency differed (p less than 0.05) from that of the general population, due mainly to an increased Le(a-b-) frequency. Similar immuno-haematological findings have not been reported earlier in patients with rheumatological diseases. If confirmed by other centres, the results may be of importance for our understanding of the immunological mechanisms of chronic inflammatory connective tissue diseases.

Another case of a lymphocytotoxic antibody with blood group A1 Leb and A Led associated specificity.

A lymphocytotoxic antibody with blood group A1 Leb, and A (A1 + A2) Led, associated specificity was found together with an anti-HLA-DR2 in the serum of a multiparous woman. The A1 Leb and A Led-antibodies could be absorbed with erythrocytes from persons with blood group A1 or A2, irrespective of their Lewis antigens, even if their lymphocytes reacted negatively in this antibody, leaving anti-HLA-DR2 in the serum. Lymphocytes of blood group A1 were able to absorb the anti-A1 Leb and -A Led, whereas those of A2 could only absorb the anti-A Led. Saliva from persons with blood groups A1 Le (a - b +), A2 Le (a- b +), A1 Le (a - b -), secretor, and A2 Le (a - b -), secretor, inhibited the anti-A1 Leb and -A Led when tested in the serum/saliva ratio 50:1, which was not the case with other ABO-Lewis combinations. The woman who produced this antibody has blood group O Le (a - b +) and secretes H, Lea and Leb substances in about the same amount as do other individuals with blood group O Le (a - b +) used as controls. The anti-A in her serum has equal titers against A1 Le (a + b -) and A1 Le (a - b +) red cells.

The comparison between normal and Epstein-Barr virus-transformed homozygous typing cells and their use for MLC, PLT and serological detection of human Ia-type alloantigens.

Normal human lymphocytes isolated from freshly drawn blood were repeatedly stimulated (up to five times) in mixed lymphocyte cultures (MLC) with five different Epstein-Barr virus (EBV)-transformed homozygous typing cells (HTC-LCL). Each time, the same WDW-specificity was used for the restimulation. The first and the second stimulations resulted in an 2.4- to 3.1-fold increase of the original responder cell number. But after the third, fourth and fifth stimulation decreasing amounts of specifically primed lymphocytes were recovered. Primed lymphocyte typing (PLT) showed significant differences in the intensity of the stimulation depending on whether homozygous typing cells (HTC) or HTC-LCL were used as stimulators. Except for one cell type, the PLT-response was significantly stronger with HTC-LCL than with HTC. The time needed to reach the maximal PLT-response got shorter and shorter the more often the cells were reprimed by the same stimulator cell. Further differences between HTC and HTC-LCL were observed in the complement-dependent cytotoxicity assay: HTC-LCL were more sensitive towards rabbit complement and they showed an enhanced binding of anti-Ia-alloantibodies but HTC reacted more specifically with the antibodies.

HL-A antigen, gene, and haplotype frequencies in Denmark.

Between 426 and 1,967 unrelated Danes have been HL-A typed for most presently known HL-A antigens of the LA (first), FOUR (second), and AJ (third) segregant series. Antigen, gene and haplotype frequencies with delta values are given. AJ series antigens are most strongly associated with some of the FOUR series antigens, and except for one case, the linkage disequilibrium between AJ and FOUR does not seem to be influenced by the LA series; the exception concerns HL-A9, RH-315, and 12: the RH-315 determinant is significantly more frequent on HL-A9, 12 haplotypes and on other HL-A12 carrying haplotypes. The term "superhaplotype" is suggested for gene constellations such as the HL-A9, RH-315, 12 "haplotype". It is suggested that the associations between cross-reacting antigens from one series with the same antigen from another series may reflect recent evolutionary divergence of the cross-reacting antigens.