bluuebunny/crossref_metadata_2025 huggingface dataset:
The Crossmatch in Renal Transplantation*
Authors: Morris Peter J. , Ting Alan
Published: July 2010

During the past 4 years, 60 renal transplants (out of a total of 191) have been performed in the presence of a positive crossmatch between recipient serum and donor lymphocytes, in a lymphocytotoxic assay. Forty‐five grafts had a positive B‐cell crossmatch and 15 had a positive T + B cell crossmatch. The results of these transplants at both 1 month and in the long term, as assessed by actuarial survival curves, are similar to those seen where the transplant was performed with a negative crossmatch.

Of the 45 recipients with a positive B‐cell crossmatch, reactivity with autologous lymphocytes was tested in 30, and 14 proved to be positive. Their survival rate was higher than that seen in the B‐cell positive crossmatch transplants not due to autoreactive antibodies, although the difference was not statistically significant. Of the 15 recipients with a positive T + B cell crossmatch 13 proved to be due to autologous reactivity. Again the survival rate was higher than that seen in the negative crossmatch grafts.

Two‐thirds of the positive crossmatch grafts were implanted into recipients with antibodies reacting with over 85% of random panel cells. These patients would be considered extremely difficult or impossible to transplant in units with a policy of transplanting only with a negative crossmatch.

Overall, our results show that donor‐reactive B‐cell antibodies and T + B cell antibodies which are autoreactive are not associated with increased graft failure. However, we have noticed a relatively high non‐function rate in the positive crossmatch transplants (particularly B‐cell positive). This suggests that there is still considerable heterogeneity of the antibodies which may give rise to a B‐cell positive crossmatch, and although most of these antibodies are harmless, it does seem that some are damaging. Thus it is important to further characterize the specificities of these antibodies and determine their effect on a subsequent renal allograft.
Do Alleles in Linkage Disequilibrium Compensate for each other's Disadvantageous Effects?
Authors: Welsh K. I. , Amlot P. , Batchelor J. R.
Published: July 2010

When alleles from two different loci behave as independent factors it is possible to calculate the expected frequency of their joint occurrence. In the HLA system significant departures from expected haplotype frequencies occur. Thus antigen B8 occurs together with A1 or/and DR3 in about 95 cases out of 100 (the figure expected by chance is about 45 out of 100). In a similar manner the antigens A3, B7 and DR2 are found associated very much more often than expected by chance alone. The reasons for these observations are obscure, but Fisher (1930) and more recently Bodmer (Bodmer & Bodmer 1978) have argued that some form of natural selection is a major factor in the occurrence and maintenance of linkage disequilibrium. In the present study we show that individual alleles of the common haplotype A1—B8—DR3 can exert different effects as regards IgE levels. This may provide evidence that one of the contributory mechanisms leading to linkage disequilibrium involves selection against individuals having a harmful allele unless it is in association with another conferring compensatory effects.
Aspects of the Primed Lymphocyte Typing (PLT) Technique
Authors: Morling N. , Platz P. , Ryder L. P. , Svejgaard A. , Thomsen M.
Published: July 2010

The influence of different culture conditions in the primary and secondary cultures of the primed lymphocyte typing (PLT) technique was investigated with special reference to the discriminatory capacity of the PLT‐cells generated. In the primary cultures, the maximal yield of PLT‐cells was observed early (about day 7) and decreased thereafter, while the maximal specificity was obtained considerably later (about day 14).

In the secondary cultures, the optimal culture time was in the interval 42 h ‐72 h, and up to this culture length, γ‐irradiation (2,200–8,800 rad) of the secondary stimulators had no effect on the 14C‐thymidine uptake of the cultures. In U‐form microtiterplates, the number of PLT‐cells per well should not be less than 2.5×104, and higher PLT‐cell numbers (e.g. 5.0×104 per well) may confer further robustness upon the technique. The PLT‐cell response and the discrimination was only slightly influenced by the number of secondary stimulator cells in the interval 5×104 to 2 × 105 cells per well. Freezing of the PLT‐cells under controlled conditions resulted in a minor loss of viable eosin‐excluding cells, while the specificity of the PLT‐cells was unaffected.

Even when the culture conditions are standardized, it is necessary to perform a normalization of the data in order to obtain reproducible results. The normalization procedure should include a compensation for the variation in (i) the general responding capacity of each PLT‐cell and in (ii) the general stimulatory capacity of each secondary stimulator.
The Association of Goitrous Autoimmune Thyroiditis with HLA‐DR5*
Authors: Farid Nadir R. , Sampson Laura , Moens Hilda , Barnard John M.
Published: July 2010

We found HLA‐DR5 to be present among 53% of 40 patients with goitrous autoimmune (Hashimoto's) thyroiditis compared to 26% of 80 controls. No deviations from those expected in the incidences of HLA‐A, B, C antigens were seen. In contrast HLA‐DR3 was increased among 50 patients with atrophic thyroiditis (65%) compared to controls (24%). These findings stress the immunogenetic heterogeneity between the goitrous and atrophic varieties of thyroiditis.
Synergism and Gene Dose Effect in HLA‐DR Serology
Authors: Madsen Melvin
Published: July 2010

By mixing HLA‐DR antisera of different specificities and testing them against B lymphocytes carrying the corresponding antigens, a synergistic action of HLA‐DR antibodies was revealed. Furthermore, it was demonstrated that HLA‐DR and HLA‐ABC antibodies may act synergistically against appropriate B cells. HLA‐DR homozygous B lymphocytes were found to react more strongly with HLA‐DR specific antisera than heterozygous cells, thus revealing a gene dose effect in HLA‐DR serology.

ABO antibodies were found not to react against B lymphocytes, either alone nor in concert with HLA‐DR antisera. The practical implications of synergism and gene dose effect in HLA‐DR serology are discussed.
HLA Associations with Insulin‐Dependent Diabetes Mellitus in a Sample of the American Black Population*
Authors: Reitnauer Pamela J. , Roseman Jeffrey M. , Barger Bruce O. , Murphy Catherine C. , Kirk Katherine A. , Acton Ronald T.
Published: July 2010

It has been of considerable interest to determine if the HLA associations with insulin‐dependent diabetes mellitus (IDDM) in blacks are the same as in whites in the United States. Seventy‐nine black IDDM patients who were under the age of 40 at onset and 283 black controls were HLA typed for A, B and C specificities. This is the largest sample of black IDDM patients yet reported. Analysis of HLA antigen frequencies for these samples has revealed an increased frequency of HLA B8 (p<0.01), B13 (p<0.02) and B15 (p<0.006), and a decreased frequency of B14 (p<0.01). The estimate of relative risks for B8 and B15 was 2.6 and 4.4, respectively. Comparison of a subsample of the black patients (n= 61) and controls (n=137) revealed increased frequencies of DR3 (p<0.0004), DR4 (p<0.0002), and DR7 (p<0.03) in the IDDM patients. Both HLA DR2 and DR5 were decreased in the diabetic patients (p<0.0()01 and p<0.0002, respectively). All p values were uncorrected. The associations of HLA antigens with IDDM in our black American sample are essentially the same as those found in white IDDM patients. This suggests that the occurrence of IDDM in American blacks may be due to admixture of white genes.
Histocompatibility Determinants in Israeli Jewish Patients with Coeliac Disease: Population and Family Study
Authors: Brautbar C. , Freier S. , Ashkenazi A. , Dekelbaum R. , Tur‐Kaspa I. , Amar A. , Cohen I. , Sharon R. , Abecassis R. , Levene C. , Cohen T. , Albert E.
Published: July 2010

The association between HLA and coeliac disease (CD) was studied in the Jewish population of Israel. A total of 112 patients were typed for HLA‐A,B,C antigens, including 67 patients whose families were typed in order to deduce the genotypes. Forty‐seven patients were typed for HLA‐DR antigens. The HLA‐A,B,C data show a pattern of association, which is similar to that found in European CD patients: HLA‐B8 is increased, although to a lower degree; a suggestive, insignificant increase for Aw30, B13 and Cw6 and a decrease of Bw35 were noted. The DR antigens DR3 and DR7 are associated with CD in the Jewish population. An excess of DR3/DR7 heterozygotes was noted. The data from family and population studies support a model in which two different HLA‐DR associated genes are intereacting.
Strong Association of Idiopathic Membranous Nephropathy (IMN) with HLA‐DR 3 and MT‐2 without Involvement of HLA‐B 18 and no Association to BfF1
Authors: Müller G. A. , Müller Claudia , Liebau G. , Kömpf J. , Ising H. , Wernet P.
Published: July 2010

The present study investigated the distribution of HLA‐antigens and Bf alleles in a group of 21 patients suffering from biopsy proven Idiopathic Membranous Nephropathy (IMN). A statistically significant increase of HLA‐DR3 (76.2%) was detected in the patient group as well as an increase of MT‐2 (86%), which is a new supertypic specificity defined within the 8th International Histocompatibility Workshop 1980. No association between BfF1 and IMN can be deduced from this study. Only the common Bf alleles (BfFF, BfFS, BfSS) were found in the patient group presented here. Also the previously reported association between HLA‐B18 and IMN was not corroborated by this study. Not a single IMN‐patient typed positive for HLA‐B 18. Thus the presence of two different HLA‐DR‐Bf‐B linkage groups (HLA‐DR3/BfF1/HLA‐B18 and HLA‐DR3/Bf; all alleles/HLA‐B8) may point to at least two different immunological mechanisms underlying IMN.
Studies on an Isolated West Indies Population: I. Analysis of HLA Genotypes
Authors: Fumeron Frédéric , Feingold Nicole , Bois Etienne , Mayer Francine , Hors Jacques
Published: July 2010

The transmission of HLA genes was studied in an isolated population of French origin on the lesser Antilles islands in the West Indies. The study of 74 unrelated individuals, 44 of whom were genotyped, was carried out for the alleles of HLA loci: A, B, C and Bf (proactivator factor of properdin).

As a result of the founder effect and the inbreeding process, the HLA haplotypcs were noted to be less polymorphic than in a French continental population. Two haplotypes: A2, Cw5, B12, BfS and A3, C‐, B14, BfF represent 24% of the observed haplotypes, and only 2% of the reference haplotypes in France.

No significant excess or deficit of homozygotes was observed at the A and B loci.
The HLA Antigens of Two Negrito Populations in the Philippines
Authors: Horai Satoshi , Omoto Keiichi , Juji Takeo , Sonozaki Hidekichi , Mitsui Hiroshi , Misawa Shogo , Sumpaico Joaquin S. , Mercado Alfredo S.
Published: July 2010

HLA antigens were determined for the A, B and C loci among 86 Aetas of west‐central Luzon and 87 Mamanwas of north‐eastern Mindanao, Philippines. The overall antigenic profiles of these two groups were essentially similar to those of other Asian‐Pacific populations with some peculiarities in common with Papua New Guineans. However, the results of heterogeneity tests and the comparison of statistically significant phenotypic associations showed a highly significant difference between the Aeta and the Mamanwa groups. It was postulated that the two “Negrito” groups represent different migrations to the Philippines.
Abortion May Sensitize the Mother to HLA Antigens
Authors: Gelabert A. , Balasch J. , Ercilla G. , Vanrell J. A. , Vives J. , González‐Merlo J. , Castillo R.
Published: July 2010

The incidence of cytotoxic antibodies in relation to histories of abortions was analyzed in sera from 474 nulliparous pregnant women. In patients with previous spontaneous abortions, there is a higher incidence of positive sera than in primigravidae. Furthermore, patients with two or more prior abortions show a greater incidence of cytotoxic activity in their sera than women who have had only one abortion.
Characterization of Antibodies Reacting with Husband's Lymphocytes in Sera from Patients with Trophoblastic Malignancies
Authors: Tursz Thomas , Lipinski Marc , Guillard Maryvonne , Dutheil Marcelle , Boomer Julia G. , Amiel Jean‐Louis , Bodmer Walter F.
Published: July 2010

Lymphocytotoxic antibodies reacting with husband's lymphocytes were demonstrated in 24 sera from women with trophoblastic neoplasia studied before any chemotherapy.

These antibodies exhibited a maximal cytotoxic activity at +4°C. They reacted mainly with B lymphocytes as assessed by microlymphocytotoxicity assays using B‐or T‐cell enriched subpopulations and T‐or B‐cell lines as targets. They could not be absorbed out with platelets or erythrocytes, and did not react with autologous lymphocytes.

In one double‐labelling immunofluorescence experiment, these antibodies could be stained by rhodamine‐conjugated Fab'2 anti‐μ fragments and thus appeared to belong to the IgM class. They were shown to react mainly with surface Ig (SIg) bearing lymphocytes, plus a minor SIg negative subset.

Studies with panels of allogeneic normal B cells and of HLA homozygous B‐cell lines showed that the target antigen(s) recognized by these antibodies is clearly distinct from HLA‐D antigens. Corresponding antigens seem to be expressed on placenta, since the lymphocytotoxic antibodies could be absorbed out with trophoblastic homogenates and one serum reacted with JAR cells (cultured choriocarcinoma line).

An enhancing role of such antibodies in the growth of trophoblastic malignancies may be suggested.
Functional Cell Mediated Lympholysis: II. Genetics1,2
Authors: Goeken Nancy E. , Thompson John S.
Published: July 2010

The diminished response to secondary stimulation of human lymphocytes primed in bi‐directional (BD) mixed lymphocyte culture (MLC) has been demonstrated to be due to cytotoxic destruction of the responder cells by the numerically superior allogeneic stimulating cell population. This phenomenon is called Functional Cell Mediated Lympholysis (F‐CML). Matching for HLA‐A and B, HLA‐DR or for MLC non‐responsiveness (HLA‐D) in unrelated pairs does not ablate F‐CML, indicating that none of these loci serve as the exclusive target for this activity. One locus appears to be centromeric from HLA‐A in an A/B recombinant family and a B/D recombinant family demonstrates a target centromeric from HLA‐B. A special family with homozygous for HLA‐A, B and D provided evidence for an additional locus other than HLA‐A, B or D. Thus, genetic studies indicate that at least one target antigen of F‐CML may be coded for by a locus that is centromeric from HLA‐B and which may be distinct from HLA‐D or DR.
Typing by cytotoxic lymphocytes. Genetics of HLA‐non‐A, B, C determinants—family studies
Authors: Kristensen Tom , Johnsen Hans Erik , Mossin Jette , Jørgensen Fritz , Lamm Lars U. , Kissmeyer‐Nielsen Flemming
Published: July 2010

Some CTLs recognize HLA‐structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA‐lymphoblasts in the absence of the sharing of HLA‐A, B, (C) determinants between stimulator and target lymphocytes. Based on pair‐wise correlations these CTLs form 3 clusters, identifying structures associated to HLA‐markers. Subsequent testing in 14 complete families of ± 4 children allowed the observations: (1) CML‐traits assigned on the basis of single CTLs often segregated in a non‐mendelian way or independent of HLA. (2) Assignments made on the basis of CTL‐clusters segregated with HLA. (3) in 2 informative HLA‐B/D, DR recombinant families, CML‐traits segregated with HLA‐B. (4) No haplotype could be assigned more than one CML‐trait.
HLA‐A3, B7 linkage disequilibrium in hemochromatotic patients with or without insulin dependent diabetes
Authors: Saddi R. , Muller J. Y. , Pouliquen A. , Kaplan C. , Sylvestre R.
Published: July 2010

Sixty‐six idiopathic hemochromatotic French patients were HLA‐A, B typed. The previously known strong association with A3 was confirmed (RR = 10.6, P <10–9) and our results indicate clearly that a gene implicated in idiopathic hemochromatosis (IH) determinism is located in the HLA‐A region.

The linkage disequilibrium between A3 and B7 was found to be far greater in IH patients than in controls. The authors have therefore hypothesized that this might be due to a selective advantage of this haplotype in IH. The A3, B7, Dw2 HLA haplotype has been shown to exert a protective effect against common insulin dependent diabetes (IDD). Thus the patients were divided into two groups according to the presence or absence of a definite IDD. B7 was found more frequently in IH patients without IDD but the difference is not significant.

In this context, the strong linkage disequilibrium between A3 and B7 might be due to the protective effect of the B region of this haplotype against IH secondary IDD.
HLA‐DR7 in children with idiopathic nephrotic syndrome.: Correlation with atopy
Authors: Mouzon‐Cambon A. de , Bouissou F. , Dutau G. , Barthe Ph , Parra M. T. , Sevin A. , Ohayon E.
Published: July 2010

Idiopathic nephrotic syndrome (INS) of childhood is likely to be underlain by an immunopathological mechanism; we investigated the presence of immunogenetic HLA markers in this disease. Fifty‐four unrelated INS‐affected children, among them 20 with an allergic status, were studied for 33 HLA‐A,B and 6 HLA‐DR antigens. The results were compared to those obtained in 49 children with glomerulonephritis, 28 children with atopy but without nephropathy, and 91 healthy blood donors. The HLA‐A and B antigen frequencies were not significantly different from normal frequencies. The incidence of HLA‐DR7 was significantly increased in INS‐affected patients as compared to the other groups (66.7% in patients vs 31.1% in healthy controls; corrected P value < 0.001; relative risk = 4.4), and more so in those with atopy than in those without atopy (90% vs 46%; P = 0.002). The frequency of this antigen is not increased in atopic non‐nephrotic children. No relationship between HLA‐DR7, clinical outcome and steroid‐responsiveness was found. We suggest that the pathogenesis of INS could be influenced by an HLA‐linked immune response gene, especially in its atopy associated form.
A new Epstein‐Barr virus negative Burkitt's lymphoma derived cell‐line
Authors: KALIL J. , FELLOUS M. , TANIGAKI N. , ROSA F. , PAGNIEZ C. , HERZOG C. , DASTOT H. , LENOIR G.
Published: July 2010

CHEV, a new Epstein‐Barr virus negative Burkitt's lymphoma derived cell line has been studied. Karyotype analyses demonstrated the t (8; 14) characteristic translocation. Cell surface characterisation of this line showed the presence of μ and x immunoglobulin chains and β2‐microglobobulin and the absence of the complement receptor. We are unable to detect HLA‐A, B alloantigens on the cell surface which was in contrast with an apparently normal expression of these antigens in the cytoplasm.
Mixed lymphocyte reactivity in cattle
Authors: NEWMAN M. J. , CAMPION J. E. , STEAR M. J.
Published: July 2010

Mixed lymphocyte reactivity (MLR) in cattle was assessed by measuring the extent of cellular proliferation between allogeneic lymphocytes in anin vitrotest system. To test for involvement of the bovine major histocompatibility system (BoLA) the MLR tests were done using full‐sibling cattle families which had been generated through the use of embryo transfer systems. The results showed that the responses in the MLR tests were associated with the BoLA antigen sharing status between the individuals being tested. Since the tests, were done using full‐sibling combinations, this result suggests genetic linkage between the MLR controlling antigens and the BoLA complex.
Absence of linkage between adult polycystic kidney disease and the major histocompatibility system
Authors: DYER PHILIP A. , WATTERS E. ANN , KLOUDA PETER T. , HARRIS RODNEY , MALLICK NETTAR P.
Published: July 2010

Four multiplex families affected with adult polycystic kidney disease were investigated for segregation of the disease with haplotypes bearing HLA‐A and B antigens and Bf allotypes. In no case did the disease travel with specific haplotypes within families showing an absence of linkage between the disease and the major histocompatability system. In addition, the disease was not associated with any HLA‐A or B antigen or Bf allotype either within or among the families studied.
Lymphocyte alloantigens of the horse
Authors: ANTCZAK DOUGLAS F. , BRIGHT SUSAN M. , REMICK LINDA H. , BAUMAN BEVERLEY E.
Published: July 2010

A genetic system controlling lymphocyte alloantigens of the horse is described. Alloantisera to paternal histocompatibility antigens induced as a result of pregnancy in mares were used in an antibody‐mediated complement‐dependent microcytotoxicity assay to define 15 Equine Leukocyte Antigen (ELA) specificities using cluster analysis. In this study 369 sera were screened for alloantibody using lymphocytes from 10 randomly selected, unrelated horses. A high proportion (83%) of these sera were found to be positive for antibody to lymphocyte alloantigens. After initial cluster analysis, 120 of the most discriminating sera were tested against a further 400 horses. The phenotypic distribution of the ELA antigens in 304 randomly selected horses and their segregation behavior in a family study of 161 offspring and their sires and dams indicated that 13 of the alloantigens behaved as members of a single allelic series, provisionally named locus ELA‐A. These 13 alloantigens accounted for approximately 90% of the genes at this locus. Large differences in the frequencies of some of the ELA‐A specificities were found between the Standardbred and Thoroughbred breeds of horses. Rare‘blank’alleles which were predicted by the estimated cumulative gene frequency of known alleles at ELA‐A were identified in informative families. The ELA system is probably the Major Histocompatibility Complex of the horse, although the evidence for this is not yet conclusive. The high incidence of sensitization to ELA antigens in pregnant mares suggests that the horse may be an interesting model for investigations of the maternal immunological response to fetal histocompatibility antigens.
Male infertility due to idiopathic disorders of spermatogenesis: no association with HLA
Authors: Mueller‐eckhardt G. , Krause W. , Schierke G. , Mueller‐eckhardt C.
Published: July 2010

HLA‐ABC and DR antigens were determined in 65 male patients suffering from infertility due to idiopathic disorders of spermatogenesis, and in one family including 3 brothers with azoospermia.

No statistically significant deviations of antigen frequencies were observed in the patient group when compared with 929 (ABC) or 206 (DR) healthy control individuals. From the family data, a segregation of an hypothetical disease susceptibility gene with HLA could not be deduced.
Two closely linked loci and one apparently independent locus code for bovine lymphocyte antigens
Authors: Stear M. J. , Newman M. J. , Nichola F. W.
Published: July 2010

Twenty different antigens have been detected on bovine lymphocytes. Family studies suggested that 19 of the antigens were under the control of two closely‐linked loci. The remaining antigen was apparently coded for by an independent locus. The distribution of the antigens in the population also suggested that three loci control the expression of lymphocyte antigens. A co‐capping study on two antigens which were inherited together on one haplotype showed that these antigens were expressed on different molecules on the lymphocyte membrane, providing further evidence for the existence of two linked loci.
The major histocoinpatibility complex of outbred chickens: I. Analysis of the B13 haplotype by serology and cellular reactions
Authors: Schou Marianne , Crone Monna , Simonsen Morten
Published: July 2010

The F antigens, which are serologically defined Class I gene products of the major histocompatibility complex in chickens (the B complex), were analysed in outbred birds. Private specificities of the F13 antigen from the inbred CC strain were detected in 20 outbred chickens by a haemagglutination technique. In the GVH‐in‐hibition‐release test F13 antigens from outbred and inbred chickens were identical. The L antigens, which are the Class II antigens of the B complex, were detected with specific anti L13 alloantisera by indirect immunofluorescence. Antisera defining the L13 antigen(s) of the inbred CC line reacted with all F13 positive out‐breds. As a test of one‐way direct compatibility of the inbred and outbred animals typing F13, graft versus host reactions were performed, injecting blood of F13 positive outbreds into inbred B13/13 eggs. No GVH stimulation attributable to MHC determinants was found. In MLR, responder cells from outbred MHC heterozygous chickens, which typed F13/x, were stimulated by inbred F13/13 homozygous typing cells, and weak, but significant, reactions were found. Further analysis in the accompanying paper, however, revealed no difference in the lymphocyte activating determinants (Lads) of inbred and outbred birds typing F13 and L13. No individual has yet been found which carries one of these antigens in the absence of the other.
A new B‐cell alloantigen, TB21, coded for in the HLA‐D/DR region
Authors: Maeda Hiroo , Juji Takeo
Published: July 2010

A new B‐cell alloantigen, designated as TB21, was serologically defined by 2 monospecific sera, T383 and T2200. Both T383 and T2200 had cytotoxic titers of 1:8 against TB21 positive B cells and were highly correlated to each other (r = 0.876). The phenotype frequency of TB21 was approximately 55% in the Japanese population. TB21 was strongly associated with DRw9 and weakly with DR5, but was definitely distinct from the known supertypic specificities such as MT or MB antigens. Family studies showed that TB21 segregated with different DR antigens on different haplotypes, indicating that TB21 is coded for by a gene at a closely linked but distinct locus from HLA‐DR. Furthermore, TB21 was preferentially detected on B cells but not on monocytes by complement‐dependent cytotoxicity. Failure of detection of TB21 on monocytes further distinguished the TB21 antigen from DR and MT antigens. Results of this study suggest that there exist 2 kinds of B‐cell alloantigens coded in the HLA region: DR and MT antigens, and other B‐cell alloantigens represented by TB21.
Expression of HLA‐like structures on a permanent human tumor line PC‐93
Authors: Claas Frans H. J. , Steenbrugge Gert‐Jan van
Published: July 2010

A permanent human tumor‐line PC‐93 was HLA allotyped with the use of a complement‐dependent cytotoxicity test supplemented with absorption experiments. In comparison with the peripheral blood lymphocytes of the patient, whose adenocarcinoma of the prostate was the origm of PC‐93, remarkable differences were observed. The tumor line lacked the expression of the genetically appropriate HLA‐A1, A2 and B15 antigens. Instead of these antigens, cross‐reactive HLA antigens seemed to be expressed on PC‐93, i.e. All, A28 and B17. Absorption experiments showed that the antibodies reactive with the neo‐HLA antigens were not the same as those reactive with the specific HLA antigens. This alien expression of HLA‐like structures was specific for the patients’ prostatic tumor line, as EB‐virus transformed B‐lymphocytes of the patient expressed the genetically appropriate HLA antigens.
HLA antigen frequency in erythema multiforme and in recurrent herpes simplex
Authors: Middleton D. , Hutchison T. H. , Lynd J.
Published: July 2010

In this study the HLA antigen frequency was determined in a group of patients with erythema multiforme and in a separate group of patients with recurrent herpes simplex to establish whether either disease had any antigens whose frequency deviated from that of a normal population. The frequency of HLA—B15 was significantly increased in both patient groups (P > 0.5). The increase in the erythema multiforme group does not appear to be due to the fact that some of the erythema multiforme patients have associated herpes simplex and this increase remained significant after further correction for the number of antigens tested.
Pigeon breeder's lung: association with HLA‐DR 3
Authors: Rittner C. , Sennekamp J. , Mollenhauer E. , Rösinger N. , Niese D. , Lüttkenhorst M. , Baur M. P. , Stroehmann I.
Published: July 2010

52 symptomatic (SPB) and 64 asymptomatic (APB) pigeon breeders were investigated for the HLA‐A,‐B,‐C,‐DR; C2,C3,C4 and Bf systems, and C3, C4 and factor B serum concentrations. HLA‐DR3 and Bf S frequencies were significantly higher in the SPB than the APB group. Mean factor B concentrations were lower in the SPB than in the APB group. A positive two‐way association between HLA‐DR3 and the disease was found. It is concluded that a gene or genes responsible for type III and IV allergic reactions leading to the disease is associated with HLA‐DR3. The increase of Bf S allotype and low mean factor B concentrations, however, can be explained by the strong linkage disequilibrium between Bf5 and HLA‐DR3.
Lack of association between Alzheimer's disease and histocompatibility antigens
Authors: Reisner E. , Heyman A. , Weinberg T. , Dawson D. , Ciftan E.
Published: July 2010

The present report describes the distribution of histocompatibility antigens in 52 patients with Alzheimer's disease. No significant associations were observed between this illness and particular HLA types before or after statistical correction for multiple comparisons. These findings are discussed in terms of the difficulties inherent in the clinical diagnosis of Alzheimer's disease and with regard to the choice of suitable control populations.
Immunogenetic studies of juvenile dermatomyositis
Authors: Friedman J. M. , Pachman L. M. , Maryjowski M. L. , Jonasson O. , Battles N. D. , Crowe W. E. , Fink C. W. , Hanson V. , Levinson J. E. , Spencer C. H. , Sullivan D. B.
Published: July 2010

Typing for HLA‐A and ‐B antigens was performed on 87 children with definite juvenile dermatomyositis (JDMS). A significantly increased frequency of HLA‐B8 (estimated relative risk = 2.8, Pc < 0.01) was observed among White patients, but not among Blacks or Latin Americans with JDMS. No abnormality of HLA haplotype segregation was observed among 38 healthy siblings of the JDMS probands.
Soluble HLA antigens not detected in human immunoglobulin preparations
Authors: MCLEAN I. L , FAED J. M , MILLIGAN L. M , ADAMS D. D
Published: July 2010

Immunoglobulin concentrates prepared from subjects of known HLA specificity were assayed for the presence of soluble HLA antigens by the inhibition of cytotoxic HLA alloantisera using a microabsorption procedure.

The immunoglobulin preparations inhibited alloantisera of all specificities tested, regardless of the HLA type of the immunoglobulin donor, indicating that the observed inhibition was non‐specific. Addition of extra complement reduced the inhibitory effects of the immunoglobulin concentrates.

It is concluded that the inhibition of HLA alloantisera demonstrated by this technique is due to the anticomplementary activity of the immunoglobulin preparations, rather than their content of specific soluble HLA antigens.
Monoclonal antibodies to HLA recognize monomorphic and polymorphic epitopes on BoLA
Authors: CHARDON PATRICK , KALIL JORGE , LEVEZIEL HUBERT , COLOMBANI JACQUES , VAIMAN MARCEL
Published: July 2010

Fourteen monoclonal antibodies recognizing monomorphic and polymorphic epitopes on class I and class II antigens of the human MHC have been assayed on lymphocytes of a panel of 20–150 BoLA typed bovine animals from 12 different breeds. Some monomorphic antibodies cross‐reacted and others did not. Two polymorphic monoclonal antibodies in man recognize a polymorphism in cows that follows allospecificities (BoLA‐w3, w9) already described. Immunoprecipitation experiments with monomorphic anti‐B2m and anti‐HLA‐DR monoclonal antibodies have shown that these cross‐reactions concern BoLA antigens. They also revealed that Ia‐like antigens in cattle present the same two chain features characterized in other species.
Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies
Authors: REBAÏ NAJET , MALISSEN BERNARD
Published: July 2010

The monoclonal antibodies B1.23.2 and B9.12 were developed to characterize human class I major histocompatibility gene products. They detect two different epitopes and define on a given lymphoblastoid B cell line two subsets of β2micro‐globulin‐complexed HLA class I molecules. One subset reacts with B9.12 and B1.23.2 and the other one expresses only the B9.12 epitope. Binding assays were performed on C3H mouse L cells which had been transformed with various single HLA‐class I genes and the two detected molecular subsets were shown to be encoded by different genetic loci.

Unlike B1.23.2, B9.12 detects all the β2m‐complexed molecules expressed in human B cell lines and recognizes an epitope different from the one defined by W6/32. In contrast to the vast majority of the other reported anti‐class I monoclonal antibodies (including B9.12), B1.23.2 recognizes an epitope expressed on both β2m‐associated and ‐free HLA class I heavy chains.
Association of HLA antigens, toxic reactions and therapeutic response to auranofin and aurothioglucose in patients with rheumatoid arthritis
Authors: RIEL PIET L. C. M. VAN , REEKERS PAUL , DE PUTTE LEVINUS B. A. VAN , GRIBNAU FRANK W. J
Published: July 2010

To investigate the possible relation between HLA antigens and either favourable clinical response or toxic reaction to two different gold compounds, aurothioglucose and auranofin, a new orally absorbable gold compound, we studied 50 patients with rheumatoid arthritis prospectively. Of the 25 aurothioglucose‐treated patients, response to treatment could not be evaluated in four patients because of early toxicity. Nine patients showed an excellent response, while 12 were moderate or non‐responders. Four of the 9 excellent responders were HLA‐DR3 positive, but none of the 12 moderate or non‐responders possessed this antigen (P < 0.025). In accordance with previous reports HLA‐DR3 was found more frequently in patients developing toxicity on aurothioglucose than in those who did not (RR = 5.6). No association was found between HLA antigens and favourable clinical response in 25 auranofin‐treated patients. Two of them showed a severe adverse reaction, neither of them being DR3‐positive. HLA‐DR3 positivity is associated not only with drug toxicity, but also with excellent respondership to aurothioglucose treatment.
Platelet and granulocyte specific allo‐antigens in chimpanzees
Authors: CLAAS FRANS H. J , LANGERAK JANNEKE , VREESWIJK WIM VAN , D'AMARO JOE , ROOD JON J. VAN , BALNER HANS
Published: July 2010

Chimpanzees were allo‐immunized with blood from donors, ChLA‐A and ‐B identical to the recipient. The sera of some of these animals contained antibodies that reacted only with the platelets or granulocytes of the immunizing donor and of some related and unrelated chimpanzees. Both for the platelets and the granulocytes a di‐allelic system of allo‐antigens is described, provisionally called ChPL‐1 and ChGR‐1.
Expression of H‐2 antigens and thyroglobulin (Tg) on freshly dissociated and in vitro cultured monolayers of mouse thyroid epithelial cells (TEC)
Authors: SALAMERO JEAN , MICHEL‐BECHET MARC , CHARREIRE JEANNINE
Published: July 2010

The expression of the major histocompatibility complex antigens (K, D, and Ia) and thyroglobulin was studied on both freshly dissociated and in vitro cultured murine thyroid cells. Methods used for antigen detection included direct cytotoxicity, fluorescence and electron microscopic studies. Results obtained showed that the K‐end, the D‐end and thyroglobulin antigens are expressed exclusively on the apical cell surface of thyroid epithelial cells, while Ia antigens are found on the basal part of the cell.
HLA‐DB3: population distribution and family studies of a new HLA‐D antigen associated with HLA‐DR4 in Caucasoids
Authors: Jaraquemada D. , Ollier W. , Okoye R. C. , Sachs J. A. , Festenstein H. , Grosse‐Wilde H.
Published: July 2010

On the basis of studies with 6 HTCs in four different families the new cluster DB3 identified in the 8th Workshop can be considered an established specificity of the HLA‐D series. In 112 healthy Caucasoids resident in South East England the frequency of this antigen was 2.6% similar to the frequency found in 142 Caucasoid patients with rheumatoid arthritis. The frequency in 54 unrelated Chinese individuals from Shanghai and of 120 Nigerians was 7.5% and 3%, respectively.

All Caucasoid individuals who were DB3 were also DR4 whereas no such association was found in the two other population groups.
A reanalysis of the HLA‐B7 cross‐reactive group
Authors: Darke C.
Published: July 2010

Cross‐reactivity between antigens of the HLA‐B7 cross‐reactive group (B7 CREG) was investigated by the serological analysis of 60 “broad” cytotoxic HLA antisera produced by pregnancy alone, the HLA typing of the antiserum donors and the identification of their immunizing antigens. Thirty‐five sera, made in response to B7, covered (as a group) HLA‐B7, B27, Bw42, Bw48, Bw54, Bw55, Bw56, Bw60 and Bw61 — the B7 CREG antigens. Bidirectional cross‐reactivity occurred between the B7 antigen and B27, Bw55, Bw56 and Bw60 antigens but not between the major B7 CREG antigens B27, Bw22 and B40. HLA‐B27 stimulated antisera included B7, B13 and Bw47 within their reaction range and Bw55/Bw56 cross‐reacted with Bw42, Bw54, Bw57, Bw58, Bw62 and Bw63. Bidirectional cross‐reactivity was observed between Bw55 and Bw57. Fourteen responders possessed an antigen cross‐reactive with their immunizing antigen. These findings are discussed in relation to the sharing of determinants by pairs and “families” of HLA antigens.
HLA in two islands of French Polynesia
Authors: KOSTYU D. , DAWSON D. , CIFTAN E. , STEWART A. , LEWIS D. , PARC F. , LAIGRET J. , McCOLLUM R. , AMOS B.
Published: July 2010

The HLA‐A, B, and C antigens of 243 individuals from two Polynesian islands, Maiao and Hiva Oa, have been characterized. 328 haplotypes were defined by family analysis. Most frequent antigens were A2, A11, Aw24, A26, Aw34; Bw38, Bw39, Bw48, Bw55, Bw56, Bw60; Cw1, Cw3, and Cw4. Several other antigens were present at low frequency or were present on only one island. New variants of Bw22 and B40 were found. Despite an overall similarity in antigens of the two islands, the combination of HLA‐A, B and C antigens on the haplotype were distinctive. Of 328 total haplotypes identified, 65 were unique. Thirteen of these (20%) were present on both islands. Twenty‐eight (43%) were unique to Hiva Oa and 24 (37%) were unique to Maiao. Significant, positive linkage disequilibrium values (▵) for HLA‐A, B and HLA‐B, C antigens were also different for the two populations.
Study of alleles of the second complement component (C2) on Canadian HLA haplotypes
Authors: MARSHALL W. H. , BARNARD J. M. , CHURCHILL D. , FARID N. R. , GRANDY R. , LARSEN B. , PAYNE R. H. , SKANES V. M. , EBERS G. C. , PATY D. W. , MERVART H. , SCHROEDER M. L.
Published: July 2010

Typing for genetic variation in the second complement component C2 was performed on sera from HLA haplotyped Canadian families. Part of the data has been studied and analysed as a population; in addition there is a further random collection of haplotypes bearing the C2*2 allele. In the population data there were 444 separate haplotypes from unrelated parents or other founders: 4.7% of the haplotypes carried the uncommon allele C2*2; one haplotype carried the rare C2*3. Study of C2 2–1 heterozygotes in the population data revealed 59 haplotypes which carried the common C2*1 allele and one which carried a deficiency allele C2*0. The remaining haplotypes carried either C2* 1 or else an undetectable C2*0 allele. In the entire data there were 281 meioses informative for C2. The only recombinant between HLA‐B and C2 showed the C2 locus to be on the DR side of the B locus. Strong allelic association between C2 *2 and Bw22 and less strong association between C2 *2 and B15 suggested the possibility of two ancestral C2 mutants. Examination of other markers on these and subsequently collected haplotypes do not conflict with this idea since the B15 haplotypes mostly carry C4A *4, C4B*2 whilst the Bw22 haplotypes mostly carry C4A*4, C4B*4. The alternative idea, that there was one original mutant which crossed over from a B15 to a Bw22 haplotype or vice versa is not excluded, however. Since approximate equilibrium has been reached between Bw22 and the HLA‐A locus alleles on these C2*2 bearing haplotypes, we conclude that this mutation is at least 5000 years old.

Other haplotypes carrying C2*2 are assumed to be ancestral recombinants; if this is true, the C2 locus map position between HLA‐B and HLA‐DR is confirmed. Study of C2 mutation may provide a model for understanding the genetics of some disease susceptibility genes in the HLA region.
Anti‐HLA‐A2 and ‐A28 monoclonal antibody: production and study of the cross‐reaction
Authors: BOUREL D. , FAUCHET R. , CHEVRINAIS A. M. , DEJOUR G. , MERDRIGNAC G. , GENETET B.
Published: July 2010

An anti‐HLA‐A2 and ‐A28 monoclonal antibody, XV.17, has been prepared by immunizing a Balb/c mouse with PBL. This XV.17 monoclonal antibody is a cytotoxic IgM. Its reactivity was tested by lymphocytotoxicity test and indirect immunofluorescence technique, in parallel with an alloantiserum ORA having the same anti‐HLA‐A2, ‐A28 reactivity pattern, against different panels. Family studies were undertaken. Absorptions‐elutions and cytofluorometry experiments were performed to study the cross‐reaction. The XV. 17 monoclonal antibody is cytotoxic against all the HLA‐A2 and ‐A28 tested cells, and is absorbed by HLA‐Aw23 and ‐Aw24 cell susepnsions.
HLA‐DR locus and maternal‐foetal relation
Authors: Reznikoff‐Etievant M. F. , Edelman P. , Muller J. Y. , Pinon F. , Sureau C.
Published: July 2010

Antigen HLA‐A, B sharing couples have been previously observed in abnormal pregnancies of unknown etiology. We have determined the HLA‐A, B, C and DR antigens of 20 couples with recurrent spontaneous abortions (RSAs), 32 control couples and 100 normal controls. The results showed that in couples with more than two idiopathic repeated abortions, there is no significant increase in the HLA antigen sharing couples. But we were able to observe, in the affected couples, a significant increase in HLA‐DR antigen sharing as regards the control couples. We also find a significant increase in the DR5 antigen, in both wives and husbands, in couples with repeated abortions of unknown etiology as previously described for the Dw5 antigen.
Recombination between HLA‐A and C and between HLA‐B and complement locus C4 in the same individual
Authors: Thomsen M. , Cambon‐Thomsen A. , Abbal M. , Calot M. , Arnaud J. , Ohayon E.
Published: July 2010

In a French family with 2 parents and 5 children a crossing over was found in the HLA region on both of the parental haplotypes of one of the children. The following markers were studied: HLA‐A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism. In the third child, the paternal haplotype had a recombination between HLA‐A and HLA‐C and the maternal haplotype a recombination between HLA‐B and complement locus C4. Mixed lymphocyte cultures confirmed the serological findings and non‐HLA markers (blood groups and immunoglobulin allotypes) showed no evidence of extrapaternity. The family also demonstrates a probable duplication of the C4B1 gene in one of the paternal haplotypes.
Detection of antibodies to cell surface antigens by a simplified cellular elisa (CELISA)
Authors: Effros Rita B. , Zeller Edith , Dillard Linda , Walford Roy L.
Published: July 2010

An improved method for screening human hybridoma antibodies to cell surface antigens is described. The following modifications have been developed: (1) rapid expansion of desired screening cell types by EBV transformation; (2) use of only 5 × 104 cells/well; (3) elimination of the need for glutaraldehyde fixation; (4) elimination of the requirement for PLL to attach cells to microplates; (5) preparation of a large number of plates which can be stored at 4° for 3 months; (6) Protein A‐peroxidase ELISA assay yielding excellent replicates, low background “noise”, and high OD readings for positive wells. The techniques we have developed should greatly simplify and shorten the assay procedures for detecting human antibodies to a variety of cell surface antigens.
Platelet absorption on the test tray (PATT): A rapid method for the screening of HLA class II antibodies using the two‐colour fluorescence method
Authors: Cambon‐Thomsen A. , Sommer E. , Demur C. , Calot M. , Ohayon E.
Published: July 2010

Several strategies have been proposed for the screening of alloantisera towards HLA class II antigens. Most often the absorption of the sera with platelets is required in order to remove their anti‐HLA‐A, B, C activity. We have developed a simple micromethod for platelet absorption of sera: platelet absorption on the test tray (PATT); 0.5 μl of platelet suspension is incubated with 0.5 μ1 of the serum to be absorbed in the same tray which is subsequently used for the microlymphocytotox‐icity by the two‐colour fluorescence method. This technique is proved to be almost as efficient as classical absorption procedures: out of 44 anti‐HLA‐A, B sera the T‐sell activity is completely removed in 43 by a classical procedure as compared to 41 by PATT; only 8% discrepancies were found among 394 reactions. PATT was then used for anti‐B lymphocyte screening in 419 anti‐HLA‐A,B sera: 4% of the sera remained cytotoxic towards T and B lymphocytes while 35% reacted only with B cells, several of them being DR specific. PATT can also be useful for T/B lymphocyte differential cross‐matches before kidney transplantation. The method is now routinely used in our laboratory for anti‐HLA class II antibody screening.
Natural HLA antibodies
Authors: Tongio M. M. , Falkenrodt A. , Mitsuishi Y. , Urlacher A. , Bergerat J. P. , North M. L. , Mayer S.
Published: July 2010

“Natural antibodies” directed against antigens of the Major Histocompatibility Complex have been observed in aged mice but very seldom in humans. It is likely that HLA natural antibodies are more common than previously supposed: our results suggest they may be found in 1% of normal blood donors. Most of these antibodies seem to be weak and can only be detected when B lymphocytes (BL) are used as target cells in the lymphocytotoxicity technique or when indirect immunofluorescence is used with peripheral blood lymphocytes (PBL). The behavior of these natural IgM antibodies was compared to that of weak immune IgG HLA antibodies detected in the same way. Absorption tests showed that “natural antibodies” were very specifically absorbed, whereas “immune antibodies” could also be absorbed by cells not carrying the specific antigen. Furthermore, about half of the “natural antibodies” detected to date carried the HLA‐B8 specificity. Various hypotheses have been put forward to attempt to explain the appearance of these antibodies.