Is HLA-DR3 a risk factor in PLA1-negative pregnant women?
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Biomedical subjects
Publications and source records attributed to F Décary.
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We have examined the distribution of HLA antigens in 70 multiple sclerosis (MS) patients divided in three groups defined according to clinical criteria: benign MS, severe MS, cerebellar MS. We have found a significant association between severe MS and HLA-DR2, and between benign MS of more than 15 years of evolution and HLA-DR3. We review previous work along the same line and conclude that the association of HLA antigens with "clinical subgroups of MS" could indicate a genetically based heterogeneity of the disease and offer help in establishing a prognosis.
Thirty-two patients with older age onset rheumatoid arthritis (ORA), defined as disease onset after age 60, were selected for HLA typing. The majority (69%) were rheumatoid factor (RF) seronegative. An increase in HLA-DR4, though not statistically significant, was seen in ORA (38% vs 17% normals). This antigen was strongly associated with RF seropositivity (70%, p less than 0.01) and rheumatoid nodules (75%, p less than 0.01) in ORA. We conclude that the immunogenetics of ORA are similar to that described for adult RA in general.
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The clinical features, therapy and course of disease in a group of 34 patients with older age onset rheumatoid arthritis (ORA) defined as disease onset after age 60 are compared with a group of 34 rheumatoid patients whose disease onset began at a younger age (YRA). Onset of rheumatoid arthritis (RA) beyond age 60 is not uncommon as ORA represented 33% of all RA patients seen in our rheumatic disease unit. The ORA patients had a shorter mean disease duration (p less than 0.001) and a tendency to less rheumatoid factor seropositivity (p = 0.06) despite random selection for active disease of less than 10 years' duration. Suppressive therapy was employed less frequently in ORA (p less than 0.01) than in YRA but the use of other therapeutic modalities and the last recorded functional class were similar in the 2 groups. ORA patients did have greater functional incapacity at some point in their disease course (p less than 0.01) as well as a greater frequency of weight loss (p less than 0.001) and other acute systemic features at onset than YRA patients. Seronegative ORA appeared to have a favourable disease course in comparison with seropositive ORA.
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Twenty-five patients with adult Still's disease were studied to determine clinical course and possible HLA associations. Two types of disease evolution were distinguishable clinically: a self-limited remitting disease with or without recurrent cyclic exacerbations was found in 11 patients, and a persistent disease with continuous activity for more than 1 year, generally accompanied by progressive joint disease, was determined in 8. Disease course could not be classified in 6 patients. The antigen frequencies of HLA-Bw35 (40%, P less than 0.05) and Cw4 (44%, P less than 0.05) were increased in adult Still's disease as compared to controls (18% and 20%, respectively). Because HLA-Bw35 was associated with self-limited remitting type disease (P less than 0.02), this antigen may be a favorable prognostic marker in adult Still's disease.
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Two cases of neonatal alloimmune thrombocytopenia are presented. Using the indirect immunofluorescence test on platelets in suspension, the presence of non-agglutinating platelet specific antibodies with the specificity anti-Zwa could be demonstrated. In both cases diagnosis of alloimmunization was made before delivery of a second child, typing of the family was done and recommendations could be made concerning clinical management. Compatibility testing between the mother's serum and donor platelets (Zwa-negative) was predictable of a normal transfused platelet survival in the newborn.
Two hundred and eight pregnancy sera were tested for the presence of antibodies specific for lymphocyte sub-populations by using the isolated B and T lymphocytes from the women's mating partners. This was done by the microlymphocytotoxicity and the indirect immunofluorescence techniques. Five sera (2.5%) reacted exclusively with B lymphocytes and sixty-three sera (30.2%) reacted with both B and T lymphocytes; none of the sera was specific for T cells. Several sera, reacting with both B and T lymphocytes, were absorbed with platelets and this procedure revealed nine additional antiseraa specific for B lymphocyte antigens. Specificity studies on a panel of forty-eight HLA-ABCD typed individuals indicated that most antisera possibly defined new B-cell antigens. Family studies established that the antigens defined by these antiser were coded for by genes in the Major Histocompatibility Complex.
During the VIIth Histocompatibility Workshop, 44 sera were selected that defined B-cell alloantigens showing correlation with the HLA--D antigenic determinants. The segregation of these antigens, now called DRw (HLA--D-related), was studied in a family that contained one HLA--A/B recombinant and one HLA--B/D recombinant sibling. It could be established that the DRw-1 antigenic determinants segregated with the B-D region in the A/B recombinant sibling and that the DRw-2 antigen segregated with the D region of the B/D recombinant child. In the second family, DRw typing segregated with the D region of the B/D recombinant child. In the second family, DRw typing showed that one of the children was identical with an HLA--ABC non-identical sibling. This suggested that a crossing-over had occurred. This was confirmed by mutual non-stimulation of these HLA--ABC non-identical children in the mixed lymphocyte culture. This crossing-over involved the DRw-3 alloantigen. These data confirm the assumption that serologically defined B-cell alloantigens are coded for by genes located outside the HLA--A/B region on the B-D side of chromosome. Moreover, these data suggest that, within families, serological B-cell genotype identity can predict a mutual unresponsiveness in the lymphocyte culture. However, findings in these two families indicate that discrepancies nevertheless exist between B-cell serology and mixed lymphocyte reactions and that mutual stimulation can occur despite apparent identity of serological B-cell phenotype and that B-cell phenotype identity does not necessarily predict mutual unresponsiveness in the mixed lymphocyte culture.
The serum of a 39-year-old male under long-term platelet transfusion therapy for hypoplastic anemia with thrombocytopenia was investigated for the presence of leukocyte and platelet antibodies after the patients had received platelet concentrates from more than 700 random donors. The serological studies of his serum revealed: (1) the absence of platelet-reactive antibodies; (2) the absence of agglutinating or cytotoxic antibodies against leukocytes; (3) the presence of at least two granulocyte-specific antibodies, one with the specificity anti-NA2 and the other with an undefined specificity, both only detectable by indirect immunofluorescence, and (4) the presence of cytotoxic-negative fluorescence-positive peripheral-blood-mononuclear-cell-reactive antibodies, not directed against HLA-A, B or C antigens. The significance and implications of these findings are briefly discussed.
Capping, independent of metabolic energy, of surface immunoglobulin (S-Ig) on 'Hairy cells' from patients with Hairy cell leukaemia (HCL) is described. As controls leukaemic cells from a patient with a prolymphocytic leukaemia (PLL) and blood lymphocytes from healthy individuals were used. The specificity of the energy-independent capping of the HCL-cells as compared to the controls was tested by incubation of the cells at 4 degrees C in the presence of 0.1 M sodium azide with different FITC-labelled ligands. In order to find an explanation for this phenomenon, the influence of cytochalasin B, colchicine and the combination of both drugs on capping of S-Ig and concanavalin (Con-A)-receptors at 37 degrees C was investigated. Furthermore the effect of Con A on S-Ig capping and vice versa was studied. The results show that only S-Ig on HCL cells could form caps at 4 degrees C in the presence of sodium-azide. Cytochalasin B alone induced a strong inhibition of Con A capping on all 3 cell types, whereas S-Ig capping was unaffected. Colchicine alone had practically no effect. Anti-Ig inhibited subsequent patch and cap formation with Con A on both HCL cells and PLL cells, whereas Con A caps and patches were redistributed by anti-Ig on PLL cells, but not on HCL cells. Conversely, Con A could link S-Ig to other receptors, leading to inhibition of S-Ig capping at 4 degrees C on HCL cells and to co-capping of S-Ig at 37 degrees C on both cell types. In addition Con A induced redistribution of S-Ig caps. The combination of co-capping of S-Ig by Con A, followed by redistribution of the caps by FITC-anti-Ig simulated inhibition of S-Ig capping by Con A on PLL cells. The major conclusions are: in some cases inhibition of capping may actually be caused by redistribution of caps; the energy-independent capping cannot be explained by free diffusion of S-Ig in the membrane through lack of any connexion with receptor-mobility regulating systems. It is proposed that the energy requirement of capping is needed to inactivate a specific mechanism,w which restrains receptor mobility and which is non-operative in HCL cells.
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An indirect immunofluorescence technique for the detection of alloantibodies against granulocytes was developed. A major problem was the unspecific fluorescence of granulocytes, due to unspecific adherence of immunoglobulins to the cell membrane. This could be suppressed by the prefixation of the granulocytes with paraformaldehyde. The developed test proved to be specific and sensitive and to have a high reproducibility. Strongly positive reactions were obtained with antisera containing granulocyte-specific agglutinins or granulocyte-cytotoxins, but also with some sera that did not react in either the agglutination or the cytotoxicity test. HLA antisera also gave positive reactions, but strong anti-A, anti-B or anti-D sera did not react. With this technique leucocyte antibodies can be detected in a higher percentage of patients with febrile transfusion reactions.