bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological Characterization of Human Monocytes for HLA, B‐Lymphocyte, Granulocyte, and Monocyte‐Associated Antigens by Cytotoxicity Testing
Authors: Drew S. Ian , Nathanson David S. , Zamfirescu P. , Carter B. M. , Terasaki Paul I. , Naiem Faramarz , Billing Ronald
Published: December 2008

Highly enriched preparations of monocytes, B and T lymphocytes, and granulocytes from 18 normal donors were serotyped in parallel in a complement‐dependent cytotoxicity assay using allogeneic and heterologous antisera defining three independent tissue antigen systems. HLA and B‐lymphocyte tissue antigens were detected on human monocytes although granulocyte antigens were absent. By cytotoxicity testing the presence of la‐like antigens on monocytes was significantly diminished compared to the autologous B‐lymphocyte population and has important implications in B‐lymphocyte serology. The study indentified a number of human antisera obtained from multitransfused subjects and pre‐and post‐transplant organ recipients that were non‐HLA and appeared to define monocyte‐associated antigens. The Serological implications of surface antigen expression on human monocytes compared with other peripheral blood cells are discussed.
Tuberculosis Associated with HLA—B8, Bf S in a Newfoundland Community Study
Authors: Selby R. , Barnard J. M. , Buehler S. K. , Crumley J. , Larsen B. , Marshall W. H.
Published: December 2008

In three adjacent Newfoundland communities comprising some 1500 people, 589 people have been HLA typed. Forty‐six of the typed people gave a history of previous clinical tuberculosis which required treatment. Fifty‐six percent of the TB patients carried HLA B8 compared with 20% of the remainder of the population. This is a highly significant difference (P < 0.01). In each community the frequency of B8 as an epidemiological marker correlated with the incidence of tuberculosis. B8 is associated with TB in this study with a relative risk of 5.2 which compares with combined relative risks in the literature for coeliac disease and Addison's disease of 9.5 and 6.4, respectively, and which is greater than the risks for all the other B8‐related diseases. The factor B allele, Bf S, was found on all the B8 haplotypes, but the overall Bf gene frequencies in tuberculosis patients did not deviate from expected values.
False HLA—D Assignments May Be Caused by Cytotoxic Responder Lymphocytes
Authors: Kristensen Tom , Jørgensen Fritz
Published: December 2008

Lymphocytes from a healthy female repeatedly giving rise to MLC‐typing response against HLA—D homozygous typing cells of three different specificities were investigated for cytotoxic capacity by the direct CML technique. Testing against a panel indicated the presence of circulating cytotoxic lymphocytes with specificity towards HLA—A2. When tested against selected HLA—D homozygous typing cells, the pattern of CML reactivity closely resembled the pattern of MLC‐typing responses, i.e. typing responses were mostly restricted by the presence of HLA—A2 on the stimulator cells. This pattern was also found when time course studies of Cr—51 release were performed using experimental conditions identical to ordinary MLC typing, but involving chromium‐51 labeled, irradiated homozygous typing cells as targets. These studies indicate that the presence of in vivo educated cytotoxic lymphocytes among the responder lymphocytes may in some instances mimic typing responses. Such lymphocytes are thought to lyse relevant stimulator lymphocytes prior to initiation of the proliferative response.
At Least Two Loci of the Major Histocompatibility Complex Can Determine Mixed Lymphocyte Stimulation in the Rat
Authors: Günther Eberhard , Štark Otakar
Published: December 2008

Analysis of a recombinant haplotype of the major histocompatibility complex showed that two genetically separable loci (or groups of loci), LD—1 and LD—2, determine mixed lymphocyte stimulation in the rat. LD—1 maps into the H—1B region which contains the Ir genes and is associated with strong, mixed lymphocyte stimulation. LD—2 maps into the H—1A region and determines weak stimulation. LD—1 and LD—2 determinants can be detected by primed lymphocyte typing.
Idiopathic Hemochromatosis: Linkage with HLA
Authors: Lipinski Marc , Hors Jacques , Saleun Jean‐Pierre , Saddi Raymond , Passa Philippe , Lafaurie Sophie , Feingold Nicole , Dausset Jean
Published: December 2008

Forty‐eight unrelated patients with idiopathic hemochromatosis were found to have a significantly higher frequency of three HLA antigens (A3, B7 and B14) than 591 healthy controls. A significant association between HLA haplotypes and disease segregations was demonstrated in 14 family studies. A recessive inheritance of a strongly A3‐linked disease gene responsible for abnormal iron stores in the heterozygote state is postulated. The lod score value (4.415 for θ= 0.025) is compatible with this hypothesis. However, the excess of HLA‐identical pairs of affected sibs does not exclude the possibility of a pseudo‐recessiveness due to two codominant genes both HLA‐linked. For the first time, a means of screening for high risk subjects is available and therefore offers the possibility of a preventive approach.
HLA Association Studies in Black Sarcoidosis Patients
Authors: Eisenberg Harvey , Terasaki Paul I. , Sharma Om P. , Mickey Max R.
Published: December 2008

The frequencies of HLA antigens were determined in 32 black sarcoidosis patients and in 89 normal black controls. Aw23 was found in 23.6% of controls as compared with a lower frequency (6.2%) in patients (P= 0.06). No other associations were found.
New HLA—D Specificity Included in Dw7
Authors: Möller Erna , Lindblom Bertil
Published: December 2008

An HLA—D homozygous typing cell—MS—was found to induce typing responses with a phenotype frequency of 7% tested in a panel of 202 random individuals. All but two of these were positive for HLA—Dw7, which implies that the MS cell defines a split of Dw7. The new subgroup, MS, is associated with B12. Three individuals positive for MS but lacking Dw7 were found to be B13 positive. The relationship of the MS specificity to HLA—Dw11 has yet to be defined.
HLA and Disease Susceptibility: Comparative Study Between Japanese and Americans
Authors: Amos D. Bernard , Rowlands David T. , Inou Tsunamasa
Published: December 2008

Development of information about the HLA system, although still incomplete, has been greatly accelerated by international workshops. Some of these are bench type, some involve scientists from many countries and some are regional. This report summarizes a workshop‐type conference of a different kind—between scientists of two major racial groups, Caucasian and Oriental. Some specificities are common to both groups, as are the diseases they are associated with. Some diseases are associated with given specificities in Caucasians and with other specificities in Japanese, while in other instances neither diseases nor specificities are shared. The principal features of disease associations in the two groups are contrasted here. Both similarities and differences offer new approaches to studies of the nature of disease association.
Quantitation of HLA‐D Differences
Authors: Suciu‐Foca N. , Rubinstein P. , Susinno E. , Broell J. , Weiner J. , Reemtsma K.
Published: December 2008

The predictability of MLC non‐reactivity by HTC typing was tested in a single checkerboard experiment which involved 39 unrelated individuals belonging to 12 different groups of HLA‐D identical phenotypes. The strength of one‐way MLC reactions in all possible responder‐stimulator combinations (39 × 39) was quantitated by the Linear Clustering Analysis Program. Individuals who, by HTC typing, were identical for two HLA‐D antigens gave 51% negative, 36% intermediate and 13% strong positive MLC responses. Identity for only one HLA‐D antigen resulted in 3% negative, 40% intermediate and 57% strong MLC reactions. When no HLA‐D antigen was shared, 88% of the reactions were strongly positive. HLA‐D antigens behaved as equipotent stimulators in MLC between half‐identical pairs. The only exception consisted of the higher frequency of weak responses displayed by the Dw5 positive individuals against stimulators differing by LD107. The same pattern was observed when LD107 homozygous cells were used as stimulators, suggesting that determinants of this specificity might be partially included in Dw5.
Alzheimer's Disease and HLA
Authors: Henschke P.J. , Bell D.A. , Cape R.D.T.
Published: December 2008

Thirty‐four unrelated patients with Alzheimer's disease were typed for HLA‐A,‐B and‐C serological determinants. HLA‐Cw3 was increased over control antigen frequencies. This difference lost significance when corrected for the number of antigens tested.
The Distribution of HLA Antigens in the Motilones Indians of Venezuela
Authors: Johnson A. H. , Noreen H. , Spees E. K. , Villalobos H. , Serrano H. , Amos D. B. , Yunis E. J.
Published: December 2008

The HLA antigen profile of the Bari and Yupa Indians who live in the Motilones Valley on the border between Venezuela and Colombia was studied. Both groups showed very limited polymorphism. HLA‐A1, A3, A11, Aw23. A25, A26, A29, Aw30, Aw32, and Aw33, and HLA‐B7, B8, B12, B13, B14, B17, B18, Bw22, and B27 were not observed in either population.
HLA—D Typing with Homozygous Cells Identified in an American Indigenous Isolate. I. Population Studies
Authors: Layrisse Z. , Heinen H. D. , Simoney N. , Ramirez F. , Layrisse M. , Ramírez‐Stoikow Z. , García E. , Balbas O.
Published: December 2008

Lymphocytes from six individuals homozygous for their HLA—A,—B,—C and—D loci belonging to an American indigenous group, the Warao, have been used as typing cells to detect HLA—D determinants in 121 donors from the same indigenous isolate and in 71 donors of mixed ethnic origin living in Venezuela. Two determinants responsible for strong proliferation in mixed lymphocyte cultures have thus been identified. Four HLA—A2, B5 cells (r values between 0.72 and 0.57) identify a determinant provisionally called LD5a showing a gene frequency of 0.30 among the Warao and of 0.09 among the population of mixed ethnic origin. The nearest B locus antigen to this new specificity among the Warao is HLA‐B5 (r value = 0.20). A second determinant identified by two HLA—A2, B15 sisters (r values of 0.71) shows a gene frequency of 0.15 among the Warao and of 0.03 among the mixed population. The latter is related to Dw8 as shown by results of the VI and VII Histocompatibility Workshops, and is weakly associated (r value of 0.28) to HLA‐BIS among the American indigenous population tested.
Relations between the HLA‐Antigens and Immune Responsiveness to SK/SD in Healthy Japanese Subjects
Authors: Kawa A. , Matsuyama T. , Fujii H. , Nakamura S. , Ogaki S. , Ooe H. , Koreeda N. , Nomoto K. , Arima N. , Kanehisa T.
Published: December 2008

A possible association between the HLA antigens and immune responsiveness to SK/SD was studied in 90 healthy Japanese volunteers. No association was found between the HLA antigens, including B5, and SK/SD stimulated blastoid transformation. There was a week indication of an association between Bw22 and responses to SK/SD. But this was not statistically significant as far as the corrected P value was concerned.
Absorption, Elution and Blocking Studies with the Complex Antiserum ST
Authors: Verghese Margrith Wehrli , Ward Frances E.
Published: December 2008

Quantitative absorptions and elutions were performed with the broadly reactive serum ST. The major component of this serum is directed towards the B‐locus antigens Bw35, B5, and B18, which comprise the 4c CREG. A second component contains lower titered antibodies which react with members of the 4c CREG, but also appear to detect qualitative and quantitative variations associated with B‐locus specificities, B15, B17 and B8. Blocking studies indicate that these antibodies do not bind to the same sites on B8 cells as well‐defined anti‐B8 sera. These findings are discussed in terms of public specificities at the B‐locus or a new specificity at a closely linked locus.
Use of Microimmobilization and Microagglutination Assays for Attempted Detection of HLA Antigens and β2 Microglobulin on Human Sperm
Authors: Law H. Y. , Bodmer W. F.
Published: December 2008

Microtechniques for detecting sperm agglutinating and immobilizing antibodies are described. These assays are proved to be useful in the study of anti‐sperm antibodies in the sera of vasectomized men and the serum of a rhesus monkey immunized with human sperm. However, using various antisera against β2 microglobulin and HLA region antigens, including Ia antigens, in these assays, very little, if any, activity was found against sperm. Absorption and inhibition tests also could not show a significant amount of these antigens on sperm. Although no HLA region antigens could be detected in the seminal plasma by inhibition tests, a large amount of β2 micro‐globulin was found. It is suggested that some β2 microglobulin could be adsorbed onto sperm, since mouse sperm was shown to pick up β2 microglobulin after incubation with human seminal plasma. The maximum amounts of HLA region antigens and β2 microglobulin in the seminal plasma are estimated.
HLA System and Affective Disorders: A Sibship Genetic Study
Authors: Smeraldi E. , Negri F. , Melica A. M. , Scorza‐Smeraldi R.
Published: December 2008

The authors have investigated HLA‐haplotype zygotic assortment in 21 families with multiple cases of affective disorders and in 19 sibling pairs discordant for the disease. The finding of excess similarity between affected sibs stressed the possibility of the existence of genes in the HLA chromosomal region which are involved in the susceptibility to affective disorders. The mode of inheritance of such an hypothesized DS gene was also tested and some theoretical implications are discussed.
RhLA Complex of Rhesus Monkeys. X. Implications of the Association between D and Ia1 Locus Antigens
Authors: van Es A. A. , Balner H.
Published: December 2008

A high association has been found between D‐locus determinants defined by cellular methods (typing cells) and the serologically defined B cell or Ia antigens controlled by the Ia, locus. Data from recombinant offspring in two rhesus families place the Ia, locus within RhLA, in the close vicinity of the D or major MLC locus. In fact, identity between the products of those two loci cannot be excluded. Further, it was shown that cells proven to be homozygous for Ia, antigens, are nearly always typing cells (and therefore homozygous for D‐locus determinants) and, conversely, that proven typing cells carry only a single Ia, antigen and are thus probably homozygous for Ia, products. In addition, it could be demonstrated that matching for Ia, antigens greatly facilitates the detection of unrelated individuals who are mutually non‐reactive in MLC. This “predictive value” of Ia, matching has important implications for the selection of optimal donors for organ transplantation.
HLA Antigens in Two Iranian Populations: The Armenians and The Jews
Authors: Tabatabai H. , Mohammad K. , Mohagheghpour N.
Published: December 2008

The distribution of HLA phenotype, genotype and haplotype frequencies was studied in two Iranian populations, the Armenians and the Jews. Although the frequencies of most antigens in the Armenians have approximately the average Jewish values, haplotype frequencies are quite different between the two populations. The frequencies of antigens in Iranian Jews are more similar to those in the Mazandaranies, a group of non‐Jewish Iranians, than to the Jewish populations from Yemen and Cochin, India.
The HLA antigen distribution in the gipsy population in Hungary
Authors: Gyódi E. , Tauszik T. , Petranyi Gy. , Kotvász A. , Pálffy Gy. , Takács I. , NEMÁK P. , Hollán S. R.
Published: December 2008

A group of Gipsies living in two distinct geographic areas in Hungary was determined for HLA‐A,B,C,DR antigens during the 8th Histocompatibility Workshop. A quite strange distribution of HLA antigens was found after comparing the data to those of Hungarian population. HLA‐A1, Bw52, Bw22, B40, Cw1, DR2 and DRw8 are significantly increased in Gipsies, while A3, B7, B12, Cw3, DRw6 and DR7 are decreased. The strongest gametic associations were determined between the allele pairs A1/Bw61, A2/Bw52, Bw22/Cw1, DR2/Bw52 and DRw8/B40. Some deviations from the Hungarian controls were detected in the distribution of the blood groups too. Specifically, the incidence of Rh/D/ negativity and Gm/2/factor positivity is much lower and the incidence of Gm/1/ factor positivity is much higher than in the control Hungarian population. These differences between Gipsy and Hungarian populations indicate their different ethnic origin, and suggest the Middle‐Eastern roots of the Gipsy population.
An information theory quality score for reagent sera
Authors: Mickey M.R. , Mittal K. K.
Published: December 2008

A quality score adapted from information theory is of interest in evaluating HLA typing sera in that it permits the evaluation of a panel of sera detecting a given specificity from the quality characteristics of the sera considered individually. The empirical question of additivity of quality scores is considered using data of the 8th International Histocompatibility Workshop. Additivity is only approximate, which indicates that panels of sera will not be quite as good as would be predicted by summing quality scores of the component sera. Methodological problems regarding estimation of the quality score are considered. The information quality score is related to other indices of serum quality for the special case in which reactions are scored as positive or negative.
H‐Y and antigens of the major histocompatibility complex.: H‐Y and H‐2D antigens are associated on unfixed lymphocytes and thymocytes but not on testicular cells
Authors: Müller Ulrich
Published: December 2008

The results of an antibody blocking technique indicate that H‐Y and H‐2D antigens are close to one another on the surfaces of unfixed thymocytes and lymphocytes, but distant on testicular cells. The findings are the same using cells from mice of several inbred strains (C57BL/10, BALB/c, B6.H‐2k). The data indicate moreover that H‐2K antigens and H‐Y are distant on all cell types tested. The gonad specific H‐Y receptor‐presumed necessary for H‐Y directed testicular differentiation is associated with neither H‐2D nor H‐2K antigens.
Improved DR typing of cadaver donor by lymphocyte incubation
Authors: Ayoub G. , Terasaki P. I.
Published: December 2008

Of 39 consecutive cadaver donors tested, DR antigens could not be detected in 17. Following 3 h incubation of the B lymphocytes at 37°C, eight of the donors with no detectable DR antigens had two DR antigens and nine had one DR antigen. In addition, there were nine cases in which a potential cadaver donor had one antigen before incubation and two DR antigens following incubation. The simple technique of pre‐incubating B lymphocytes before testing has helped considerably in prospec‐ tively typing cadaver donors for HLA‐DR.
Sources of variance in the double normalized value: an evaluation of its reproducibility as a measure on HLA‐D locus identity
Authors: Ollier W. , Mendell N. , Sachs J. , Jaraquemada D. , Evans S. , Pegrum G. , Festenstein H.
Published: December 2008

Two different sets of mixed lymphocyte culture (MLC) experiments were performed using HLA‐D homozygous typing cells (HTC). In all stimulator‐responder combinations the median cpm's of four replicate cultures were reduced into double normalized values(DNV).

In the first experimental set the responder panel was unselected, whereas the re‐ sponders for the second set were chosen on the basis of either sharing an HLA‐D determinant with the stimulator (ID) or not (non‐ID).

The experiments were designed:

Set 1: To estimate the technical variability in the DNV's and to observe the distribution of this variability. The standard deviation of an observation on a stimulator‐responder combination was approximately 24 DNV units. Thus, by running 6 experiments on each responder we would have a mean DNV with a standard error of 10 DNV units.

Set 2: To determine whether stimulators typing for the same Dw specificity had the same distribution of DNV's and to investigate the variability between responders, between experiments and within experiments. Although the mean DNV is the same for all HTC's, the variability in observations was greater for some HTC's than for others. The variability may be completely technical for some HTC's, whereas for other HTC's there is evidence of responder variability and between experiment variability. Important implications of these results are: (1) that in using a single cut‐off value of 60 for all HTC to define typing responses one will have a very high misclassification rate for a large percentage of ID responders; (2) for some HTC this error rate can be reduced through repeating the experiment 4 times and raising the cut‐off point; (3) this error, together with the technical and/or experimental variance can be further reduced by using 2 or more HTC's of the same specificity in each experiment and by combining their data; (4) misclassification can be reduced in every situation by doing 4 experiments, using 2 HTC per responder and computing a cut‐off which gives a misclassification rate for each Dw type of 10% in ID's and in non‐ID's.

Thus the best approach to achieving Dw locus typing with a desirable low rate of misclassification would be to do similar control studies of every HTC, to estimate technical experimental and responder variance and then use this information to determine a cut‐of value and the number of HTC's and experiments per responder required to keep the error rate at a satisfactory level.
Inhibition of responder cell activity in mixed leukocyte culture reactions
Authors: de Rooij‐Doyer E. , Bruning J. W. , van Rood J. J.
Published: December 2008

In a previous report we described a human allo‐antiserum which showed MHC restricted dual specific inhibition of mixed leukocyte culture (MLC) reactions (de Rooij et al. 1980). Responder cells were preincubated with the antiserum and washed. Inhibition of MLC reactions occurred if HLA‐B8 positive responder cells and HLA‐B7 or ‐B40 positive stimulator cells were used.

The mechanism of inhibition by this antiserum was investigated and described in this report. The results strongly suggested that the observed inhibition was due to HLA‐B7 specific antibody molecules cross‐reacting with HLA‐B8 antigens. We decided on the following mechanism: HLA‐B7 specific antibody molecules bind to HLA‐B8 antigens on responder cells at 4°C. Bound antibody molecules are readily released at 37°C and then bind preferentially to HLA‐B7 or ‐B40 positive stimulator cells.

Stimulator cells are then lysed by antibody dependent cellular cytotoxicity (ADCC), resulting in impaired MLC reaction. This conclusion was derived from the following observations:

1. HL.A‐B7 positive cells could be lysed due to antibody molecules bound to B8 positive cells:

a. Cells coated with antibody molecules lysed B7 or B40 positive target cells.

b. Antibody molecules released from B8 positive cells lysed B7 or B40 positive target cells in ADCC.

2. The active antibody molecules were HLA‐B7 specific:

a. The inhibiting antibody molecules in the antiserum could be absorbed on and eluted from HLA‐B7 positive platelets (de Rooij et al. 1980).

b. Antibody molecules bound to and released from HLA—B8 positive cells carried the same B7 specific inhibiting and cytotoxic activity as the original antiserum.

3. The site of recognition on HLA‐B8 positive cells is the HLA‐B8 antigen:

a. F(ab')2 preparations from HLA‐B8 and ‐Bw6 specific antisera inhibited antibody binding to B8 positive cells.

b. Antibody binding was not restricted to B, T, FcR+, FcR‐ or non adherent cell subpopulations.

4. The antibody molecules bind to B8 positive cells with the antigen binding site and not with the Fc part of the molecule:

a. Antibody binding could be blocked partially with a F(ab')2 preparation from the original antiserum but not with a Fc preparation.

b. The antigen binding site of antibody molecules bound to HLA‐B8 positive cells was not freely available, since the MLC inhibiting activity of sensitised B8 positive cells could not be blocked by soluble HLA‐B7 antigens.

c. The antiserum was cytotoxic for HLA‐B8 positive target cells in ADCC.

The observed inhibition of MLC by antibody molecules with apparent dual specificity is thus the consequence of a shared or a similar antigenic determinant of HLA‐B7 and HLA‐B8 antigen molecules.
Haplotype study. Linkage between HLA‐A, B, C and Bf alleles: results obtained by different statistical methods
Authors: Grange D. , Tongio M. M. , Mayer S. , Hauptmann G. , Klein J.
Published: December 2008

325 HLA‐A, B and Bf haplotypes obtained from family studies were investigated. In addition, 216 of these were tested for HLA‐Cw2, Cw4, Cw5. Four different statistical methods were employed to study 2, 3 or 4 loci gametic associations in order to compare the results obtained by these different methods. Our results were then compared with those of other authors who employed similar methods. Piazza's method, used to identify gametic associations, was not able to show any 3 loci associations in our material. The Delta Standard Method employed in conjunction with Factorial Correspondence Analysis was found suitable for the study of chromosal prevalence in a population.
HLA and sporadic tuberculoid leprosy: a population study in Maharashtra, India
Authors: van Eden W. , Mehra N. K. , Vaidya M. C. , D'Amaro J. , Schreuder G. M. Th. , van Rood J. J.
Published: December 2008

A population study to test whether associations between HLA and sporadic ‐ i.e. non‐familial ‐ tuberculoid leprosy exist was undertaken in a hyperendemic area in India. Since previous family‐studies in the same area had shown both non‐random haplotype segregation in the family members affected with tuberculoid leprosy and the preferential segregation of HLA‐DR2 into tuberculoid leprosy patients, an increased frequency of DR2 among the “sporadic” patients was expected. However, no heterogeneity for HLA was detected between patients and controls. These findings could indicate that tuberculoid leprosy is a heterogeneous disease with regard to genetic background.
Vascular and renal distribution of HLA‐DR‐like antigens
Authors: Scott H. , Brandtzaeg P. , Hirschberg H. , Solheim B. G. , Thorsby E.
Published: December 2008

Tissue sections of ethanol‐fixed, paraffin‐embedded specimens from human kidney, placenta and umbilical cord were studied by indirect immunofluorescence with a rabbit antiserum to HLA‐DR antigens from B lymphocytes. Capillary walls in the kidney showed specific staining both in glomeruli and around tubuli. Conversely, HLA‐DR‐like antigens were not detected in the walls of larger vessels, in tubular cells, or in the epithelium of Bowman's capsule. HLA‐DR‐like antigens of kidney elements thus seemed to be restricted to capillary endothelial cells. In specimens from umbilical cord and placenta, HLA‐DR‐like antigens were not detected in the walls of capillaries or larger vessels. Isolated endothelial cells from the umbilical vein were likewise negative.
Studies on the role of HLA‐DR in macrophage‐T cell interactions
Authors: Bright Susan , Munro A. J.
Published: December 2008

The purpose of this paper is to illustrate the difficulties we have encountered in attempting to analyse the role of HLA‐DR in the antigen‐dependent co‐operation between macrophages and T cells which leads to a T‐cell proliferative response. We have adopted the two most commonly used approaches; attempted inhibition by anti‐HLA‐DR antisera and study of co‐operation between cells of unrelated individuals, and have found both methods unsatisfactory. With the first method we found that anti‐HLA antisera could inhibit proliferative responses in a non‐specific manner. Both anti‐HLA‐A, B and anti‐HLA‐DR antisera could inhibit and this inhibition was largely Fc‐dependent. Using pepsin‐digested antisera we have no evidence for a unique role for HLA‐DR in these proliferative responses. The second method, study of co‐operation between cells of unrelated individuals, proved extremely difficult to analyse because of the background allogeneic reaction. Whether cells of two individuals appeared to co‐operate to give an antigen‐specific response depended on the number of cells used and the calculations applied to the data. However, it was clearly possible to demonstrate co‐operation between DR different individuals.
HLA profile of the Mexican Mestizo population
Authors: Arellano Jorge , Vallejo MARTHA , Estrada Heactor Goamez , Kretschmer Roberto R.
Published: December 2008

The HLA—A, B and C profile of 665 Mexican Mestizos was studied by microcytotoxicity testing for 30 HLA specificities. Antigen, gene and haplotype frequencies were calculated, and results were compared to those of the three other series of HLA profiles in Mexican Mestizos available in the literature: one from Mexico‐City, one from Los Angeles, California, USA, and a recent one from San Antonio, Texas, USA. Comparing the antigen frequencies of our series with those of the other study from Mexico‐City, significant differences were only found in three antigens of the HLA‐B locus. On the other hand, comparison of either series from Mexico‐city with the Los Angeles or the San Antonio studies yielded discrepancies in several specificities of both HLA‐A and B loci, most notably the consistent absence of A25 in Mexican Mestizos living in Mexico‐City. The presence of this specificity in the Mexican Mestizo Population living in these two American cities could have resulted from input of Caucasian and Black genes over several generations. Differences in haplotype frequency were observed comparing the two series from Mexico‐City and the series from San Antonio. Comparison of haplotype frequency with the Los Angeles series was not possible.
HLA antigens in adults negative for antibody to Epstein‐Barr virus (EBV)
Authors: Edmond Elizabeth , Steel C. M. , Ennis Margaret , Cameron Fiona , Dick Heather
Published: December 2008

Evidence for a genetic component in susceptibility to Epstein‐Barr virus (EBV) infection was sought by comparing HLA A and B phenotypes of EBV antibody‐negative Scottish medical students and randomly chosen antibody‐positive controls. No statistically significant differences were observed, but three antigens, (AID, A29 and B15), were relatively underrepresented in the EBV seronegative group; findings which agree with data previously reported from a similar study in Los Angeles. A strong association between the HLA A1/Blank phenotype and EBV seronegativity, evident in the Los Angeles population, was not confirmed in the present study.
HLA‐DR genes and antigens in the Danish population.
Authors: Madsen M. , Graugaard B. , Lamm L. U. , Josrgensen F. , Kissmeyer‐Nielsen F.
Published: December 2008

Five hundred unrelated Danes, including 202 healthy individuals, 35 cadaveric kidney donors, and 263 patients in terminal uraemia were typed for the HLA‐DR antigens DR1—w8.

The HLA‐DR gene frequencies of healthy Danes are in good agreement with frequencies estimated during The Eighth International Histocompatibility Workshop of the Scandinavian population, but differ to some extent from other groups of European Caucasians. This indicates geographical variation in the distribution of DR genes within Europe.

Very close associations were found between the HLA‐DR antigens and their corresponding HLA‐D specificities, except for Dw4 and Dw6, which were included in DR4 and DRw6, respectively.

Linkage disequilibrium was calculated between alleles of two loci (HLA‐A,‐DR; ‐B‐DR and ‐C,‐DR) using the population data. Furthermore, linkage disequilibrium involving HLA‐DR alleles was assessed for multiple loci by using haplotype data from 32 HLA‐A,‐B,‐C,‐D,‐DR, and Bf typed Danish families.

The haplotype data showed that HLA‐DR4 is strongly associated with HLA‐B15 only in haplotypes together with HLA‐Dw4. This indicates genetic heterogeneity of HLA—DR4 which, however, does not appear serologically in this study.
HLA‐DR phenotype and HLA‐B,DR haplotype frequencies in 704 unrelated Danes
Authors: Jakobsen Bodil K. , Morling N. , Platz P. , Ryder L. P. , Thomsen M. , Svejgaard A.
Published: December 2008

HLA‐ABC and DR antigens were studied in 704 unrelated Danes (84 cadaver kidney donors, 307 healthy individuals, and 313 uremic patients). HLA‐DR1, 2, 3, 4, 7, w8, and w10 were investigated in all individuals, whereas DR5, “DRw6”, and w9 were only studied in parts of the material. The frequencies of DR1, 2, 3, 4, 5, and w10 were similar in the three groups, while those of “DRw6”, DR7 and w8 differed significantly. The deviation of the DR7 frequency was small and probably due to chance; “DRw6” is considered difficult to define, and DRw8 may have been difficult to define in the early part of the material. DR‐phenotype distributions showed perfect fits to Hardy‐Weinberg expectations for the three groups separately and for the combined group. When our combined DR antigen frequencies were compared with those from another Danish sample (Madsen et al. 1981), significant differences were found for “DRw6”, w8 and w10. However, in general, the same HLA‐B,DR phenotype combinations showed significant positive associations in the two samples, and most of the corresponding haplotype frequencies and delta values were quite similar.
HLA‐B/DR recombinant family
Authors: Mandeville Robert , Wells Linda , Dick Heather M.
Published: December 2008

A family is described in which HLA and complement allotype studies indicated two informative recombinations between HLA B and HLA DR in two generations. Both the complement components Properdin Factor B (Bf) and C4 segregated with HLA DR and Glyoxylase and not with HLA A, B, and C, confirming previous reports that their loci lie centromeric to that of HLA B.
Cellular cytotoxicity generated in a canine mixed kidney lymphocyte cell culture
Authors: Buurman W. A. , Vegt P. A. , v. d. Linden C. J. , Greep J. M.
Published: December 2008

Canine cultured kidney epithelial cells were stimulatory to allogeneic lymphocytes in mixed kidney cell ‐ lymphocyte cultures (MKLC). Generation of cytotoxic cells, cytotoxic for both kidney cells and PHA stimulated lymphoblasts of the stimulator have been observed. Lymphocyte stimulation and generation of CTL occurred in the MKLC at lower stimulator: responder cell ratios as in the mixed lymphocyte culture (MLC).
Tuberculoid leprosy and HLA in Japanese
Authors: Miyanaga Kazuo , Juji Tared , Maeda Hirao , Nakajima Seiji , Kobayashi Shigenobu
Published: December 2008

HLA phenotypes of 54 patients with tuberculoid leprosy were compared with those of 167 healthy controls. Frequencies of HLA‐A, ‐B and ‐C antigens did not differ significantly between the leprosy patients and the controls. However, an increase in the frequencies of DR1, DR2, DRW8 and MT1 antigens and a decrease in the frequencies of DR4 and MT3 antigens were observed in the leprosy patients. Statistical evidence was presented that MT1 antigens were primarily associated with tuberculoid leprosy in Japanese patients rather than DR2.
Loss of HLA‐C locus specificities from stored lymphocytes1 and de novo synthesis following incubation at 37°C
Authors: Loon J. , Terasaki P. I. , Bernoco D.
Published: December 2008

The variable expression of the C locus specificities at the cell surface is a major problem in HLA typing and the phenomenon was clearly documented by the International Cell Exchange Program. In contrast with HLA‐A and ‐B, the C locus specificities are readily lost from cells following storage at room temperature for a few days or in overnight incubation at 37°C in the presence of protein synthesis inhibitors.

These specificities can be made to reappear by making the cells metabolize at 37°C for 8 to 20 h in a nutrient medium. Sixty‐nine per cent of the positive C locus reactions lost after 7‐day storage at room temperature were recovered after overnight incubation at 37°C. The reappearance was dependent on protein synthesis since presence of cyclohexamide during incubation completely blocked the recovery. A simple overnight incubation is very useful in enhancing C locus expression on older cells.
Frequency of nine HLA—D antigens in the Danish population
Authors: Thomsen M. , Ryder L. P , Morling N. , Platz P. , Jakobsen B. K. , Svejgaard A.
Published: December 2008

The frequency of HLA—Dw1—8 and DH was determined in 389 unrelated healthy Danes and in 257 kidney patients. All individuals were HLA—A, B, C typed, 168 of the normal individuals and all kidney patients were typed for HLA‐DR.

The frequency of Dw1—8 in the normal material and kidney patient material was quite similar except for Dw6, which showed an increased frequency among the kidney patients, but as the patients are not prospectively ascertained, the significance of this finding is unclear. The frequency of the blank allele is 0.19 which is comparable to other Seandinavian materials but much lower than that seen in the joint report of the 8th International Histocompatibility Workshop. The D frequencies correlate quite well with the HLA—DR frequencies, the biggest discrepancy between D and DR exists for D/DR4, where DR4 is much “broader”. The DR4 positives can be divided into the Dw4 positives, strongly associated with B15 and the Dw4 negatives, not associated with B15 but with B40. Primed lymphocyte typing in some cases followed HLA—DR, in other cases HLA—D assignment. For HLA—D/DR2 the DR assignment also seemed to be broader, the DR2 positive, Dw2 negative group not being associated with B7, but possibly with B5.

In the assignment of HLA—D determinants, “false negatives” have caused problems in many materials, but the inclusion of a number of known control responders in our experiments has made it possible to increase the accuracy of assignment by adjusting the cut‐off level for typing responses according to the typings of the controls.
Myotonic dystrophy: HLA antigens and mitogen stimulated lymphocyte responses of a Black American family
Authors: Hsia S. , Ho C. K. , Aliffi V. B. , Doran D. M. , Hamilton D.
Published: December 2008

A Black American family of four generations with 29 members was studied. Six family members spanning two generations were affected with myotonic dystrophy. HLA A, B, C and DR antigen specificities were determined for each family member using local typing trays. Twelve HLA haplotypes were identified in the family. No significant association was found between the disease and any HLA antigenic type or haplotype. This finding suggests that the involvement of the major histocompatibility complex in the etiology of myotonic dystrophy is unlikely.

The cellular responses of twenty‐eight family members and 20 unrelated Black Americans to phytohemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM), each in three concentrations, were tested with mononuclear cells prepared from peripheral blood. There was a significant difference in responses of the affected family members as compared to the unaffected family members and the unrelated Black Americans. The PHA and PWM responses of the unaffected family members are not significantly different from those of the unrelated Black American controls; however, the Con A responses of the unaffected family members are significantly higher than those of the control group at the lowest Con A dosage. The possible systemic defects of cytoskeletal structures of the affected family members are discussed.
Cerebro spinal fluid C2 and HLA system in multiple sclerosis
Authors: Delasnerie‐Laupretre N. , Suet‐Hubert C. , Marcelli‐Barge A.
Published: December 2008

C2 hemolytic activity has been measured in serum and C.S.F. of 67 multiple sclerosis (M.S.) patients classified in three evolutionary groups according to the index of progression of the disease and tested in HLA‐A, B, C, DR and Bf. The median level of serum C2 is normal whether it is of the evolution or the HLA type. The average level of C.S.F. C2 is the same in the evolutionary groups and is low in patients bearing B18 allele or B18, DR2 haplotype. It seems that the median level of C.S.F. C2 is linked to the HLA types associated to the susceptibility gene(s) of the disease.
HLA antigens in patients with recrudescent herpes simplex infections
Authors: Legendre C. , Russell A. S. , Jeannet M.
Published: December 2008

We have assessed the humoral and cellular immune responses to HSV—I antigen in normal controls, and in 47 subjects with recurrent cold sores. The antigens at the HLA‐ABC and DR loci were examined in the first group of 21 susceptible subjects. An apparent increase in prevalence of A9 seen in this group was confirmed in a prospective study of a further 26 subjects (P < 0.0005). In contrast to previous studies, no relationship was noted between the immune responses and HLA antigens.
HLA and 21 hydroxylase deficiency: (congenital and late onset adrenal hyperplasia):in the French population
Authors: Couillin P. , Rappaport R. , Kuttenn F. , Canlorbe P. , Hors J. , Marcelli‐Barge A. , Feingold J. , Grisard M. C. , Boué J. , Boué A.
Published: December 2008

The close genetic linkage between congenital adrenal hyperplasia (21 OH deficiency) and the HLA B locus has been confirmed in a large series of French families. Two statistically significant, but moderated associations were observed: positive with HLA Bw47 and negative with HLA B8. A strong positive association of late onset with HLA B14 was observed and the results link the trait with HLA loci.
Genetic investigation in mesangial IgA nephropathy
Authors: Le Petit J. C. , Gazes M. H. , Berthoux F. C. , Loghem E. Van , Goguen J. , Seger J. , Chapuis‐Chllier C. , Marcelin M. , Lange G. De , Garovoy M. R. , Serre J. L. , Brizard C. P. , Carpenter C. B.
Published: December 2008

HLA—A, B. C. DR, MB, Bf, Gm, Am, Pi and Km genes (and 12 erythrocyte genetic systems) have been analyzed and correlated with clinical or biological features in 88 mesangial IgA glomerulonephritis.

These data pointed out 2 gene frequency modifications: a significant MB1 specificity decrease in the total patient group and a significant Km I increase in the chronic renal failure mesangial IgA nephropathy subgroup.
A monoclonal antibody recognizing a determinant common to HLA—A3 and All
Authors: Billing R. , Clark B. , Lucero K. , Shi B. J. , Terasaki P.
Published: December 2008

Spleen cells from a mouse immunized with an AML cell expressing HLA‐A3 produced a hybridoma secreting an anti‐HLA—A3, All monoclonal antibody, 26D3. By complement‐dependent cytotoxicity at dilutions to 1:104 the ascites antibody lysed 13/13 A3. 15/15 A11, and 8 other lymphocytes from a panel of 98 donors. The 26 D3 immunoprecipitated a molecule consisting of subunits of 44,000 and 12,000 daltons. Monoclonality of the antibody was demonstrated by isoelectric focusing and protein A affinity chromatography.
A method for freezing sheep lymphocytes prior to cytotoxicity testing
Authors: Stear M. J. , Allen D. , Spooner R. L.
Published: December 2008

The two stage freezing technique was adapted for use with sheep lymphocytes Parameters investigated were lymphocyte concentration, composition of thawing medium and DMSO concentration. The main difference between this and earlier published techniques is the use of a high DMSO concentration (17%). The technique adopted was both simple and reliable. It consistently gave lymphocyte viabilities of 95% or more in thawed cell suspensions. The procedure is apparently without effect on lymphocyte antigen expression and thus appears very suitable for use in microlymphocytotoxicity tests.
Soluble HLA antigens in normal human immunoglobulin preparations
Authors: Guencheva G. , Scholz S. , Schiessl B. , Albert E. D.
Published: December 2008

Nine lots of normal human immunoglobulin produeed in Bulgaria and India, prepared from venous or placcntal blood, were assayed for the presence of HLA antigens by the inhibition of cytotoxicity of HLA alloantisera using two different absorption procedures.

The results indicate that the normal human immunoglobulin preparations tested here contain soluble HLA antigens as demonstrated by the inhibition of HLA alloantisera. Most of the higher frequency antigens of the HLA‐A, B, C and DR locus appear to be present in the Ig‐preparations. In samples from India there‐ appears to be a lack of HLA‐A3 antigen, which corresponds to the low frequency of A3 in this population. Immunoglobulins produced from different raw materials contain different amounts of soluble HLA antigens.
Anti‐erythrocyte antibodies, leukocytotoxins and human renal allograft survival*
Authors: Etheredge Edward E. , Beitonville Paul , Sicard Gregorio A. , Anderson Charles B.
Published: December 2008

ABO blood group compatibility is generally required for successful human kidney transplants and new data suggest donor‐recipient incompatibility for the Lewis or multiple minor blood groups is detrimental. This is of special importance in the setting of liberal transfusions prior to transplant. To assess the impact of immunizing exposure to disparate blood groups of ABO‐matchcd transfusions and kidney transplants, we studied the interrelationships of anti‐erythroeyte antibodies, leukocytotoxins and graft survival in 42 kidney transplant recipients. Three hundred forty‐four sera were screened for anti‐erythrocyte antibodies using standard hemagglutination techniques and for leukocytotoxins, using the antiglobulin method. Statistical analysis by computer used a 2 × 2 × 2 contingency table with model fitting. Only 13 of 42 patients had anti‐erythrocyte antibodies at some time: anti‐I (4); anti‐Kell (1); cold panagglutinin (7); unidentifiable agglutinin (1). Of 42 patients, 16 had no detectable leukocytotoxins. By computer analysis, immunizations to blood group and HLA antigens were independent phenomena. Analysis showed that leukocytotoxins, but not anti‐erythrocyte antibodies, were associated with poor graft survival. A computer generated probability of graft survival by antibody status is presented. We conclude that immunization to blood group antigens is not common, is largely non‐specific, and is not detrimental to kidney graft survival.
Genetic studies of insulin‐dependent diabetes mellitus: segregation and linkage analyses
Authors: Green Anders , Morton Newton E. , Iselius Lennart , Svejgaard Arne , Platz Per , Ryder Lars P. , Hauge Mogens
Published: December 2008

The inclusion of HLA data in genetic studies of insulin‐dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygcnic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA‐DR3 and HLA‐DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA‐phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA‐DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA‐DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.