Serological study of an allergic agranulocytosis due to noramidopyrine

An allergic agranulocytosis induced by amidopyrine and triggered by noramidopyrine was studied. Leucoagglutinating and leucocytotoxic antibody, active only in the presence of the drug, was demonstrated. The antibody was stable, giving a titre from 1·34 to 1·62 and was present in the IgM (19S globulin) and in the IgG (7S globulin) serum fractions. The site of drug fixation was studied by use of iodoantipyrine labelled with ¹³¹I; a stable fixation was demonstrated on to the IgM and IgG globulins. Special emphasis is given to cross-reaction with compounds related to amidopyrine.     

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families

Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families).

• 1) 

  Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients.
• 2) 

  Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3.
• 3) 

  An excess of HLA-identical affected siblings was found.
• 4) 

  An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased.

The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.     

Analysis of the role of HLA-G in preeclampsia

Preeclampsia (PE) is a multisystem disorder of human pregnancy, occurring in 5%-10% of all population births and represents the leading cause of both fetal and maternal morbidity and mortality in pregnancy. Although the disorder only becomes clinically apparent late in pregnancy, the underlying pathology indicates that invasion of fetal trophoblasts into maternal spiral arteries during early pregnancy is shallow or absent in PE. A large number of epidemiologic studies have been carried out and they demonstrate that the disorder is highly heritable and occurs with a high incidence in all populations. Studies have shown that PE is largely under genetic control, but the mode of its inheritance remains unclear. Genetic studies have been carried out using both large scale linkage analysis and candidate gene approaches; however, the genetic mechanisms underlying the disorder have yet to be determined. We focus on the potential role of HLA-G, a nonclassical class I HLA located on chromosome 6, which appears to be a key component in trophoblast invasion. We examine the hypothesis that HLA-G may have a key role in both genetic susceptibility to, and pathogenesis of, PE.     

Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA

We performed HLA genotyping by using restriction-enzyme fragments hybridized with specific HLA probes instead of traditional immunologic methods in two patients whose lymphocytes expressed so few HLA antigens on the cell surface that serologic methods failed. Segregation of restriction-fragment-length polymorphism permitted identification of the genotypes. In addition, known correlations between serologically determined antigens and restriction-fragment-length polymorphism were confirmed. We applied this approach in making therapeutic decisions regarding bone marrow transplantation.     

Historic Landmarks in Clinical Transplantation: Conclusions from the Consensus Conference at the University of California, Los Angeles

The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contributions of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here in six tables and annotated with references.