bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA antigens and infertility with sperm autoantibodies in man
Authors: Moncharmont P. , Bielsa S. , Gebuhrer L. , Rollet J. , Silou J. , Saad A. , Betuel H. , Czyba J. C.
Published: October 2008

Vasectomized men with sperm auto‐antibodies (S.A.A.) and high frequency of HLA‐A20 antigen (Ag) were observed by Law et al. (1979); Hancock et al. (1983) observed the prevalence of HLA‐A28 in infertile men with S.A.A. HLA‐A, B and DR Ag were determined in a population of 80 Caucasian infertile men with (n = 22) or without (n = 58) agglutinating and/or cytotoxic S.A.A. in serum (S) and/or seminal plasma (SP), and the association between HLA‐determinants and infertility with S.A.A. was investigated. The frequence of HLA‐A28 Ag was found higher in the group with S.A.A. than without (18.2% vs 0.0%) but not statistically significant (X2= 8.87; pc <0.15). The same result was obtained with HLA‐B13 Ag (X2= 8.87; pc <0.32). Lastly, there was no prevalence of HLA‐DR Ag in men with S.A.A. In conclusion, no association was found between HLA‐A, B and DR Ag and infertility with S.A.A. Nevertheless, two HLA‐Ag were more frequently observed in the group with S.A.A.
HLA typing with monoclonal antibodies: evaluation of 356 HLA monoclonal antibodies including 181 studied during the 10th International Histocompatibility Workshop
Authors: Colombani J. , Lepage V. , Raffoux C. , Colombani M.
Published: October 2008

During the 10th International Histocompatibility Workshop (10th WS), 181 HLA MoAbs were studied using lymphocytotoxicity micro‐technique (LCT) and/or enzyme immuno‐assay (EIA), and their capacity to serve as typing reagents was evaluated. 129 MoAbs were tested by both techniques. Results obtained with 92 class I and 86 class II polymorphic MoAbs (10th WS) were compared to published data concerning 180 class I and 176 class II polymorphic MoAbs, listed in an HLA‐MoAbs Register maintained in our laboratory.

The following conclusions can be proposed:

1/ HLA‐A, B typing by LCT with MoAbs is possible for about 14 specificities. Some specificities are clearly recognized (HLA‐A3, B8, B13, Bw4, Bw6), others are recognized as cross‐reacting groups (B7+27+w22+40), others are not currently recognized by any MoAb with restricted specifity (B5, B15). Several MoAbs confirmed the existence of shared epitopes between products from a single locus (A2‐A28, A25‐A32), or from A and B loci (A2‐B17, Bw4‐A9‐A32). A single HLA‐Cw MoAb has been described.

2/ HLA class II typing by LCT with MoAbs is more difficult than class I typing. DR2, DR3, DR4, DR5 and DR7 as well as DRw52 and DRw53 are well defined; other DR specificities are poorly or not at all defined. Particular associations (DR1+DR4, DR3+DRw6, all DR except DR7) are recognized by several MoAbs. All DQw specificities are well recognized, including new specificities defined only by MoAbs: WA (DQw4), TA10 (DQw7), 2B3 (DQw6+w8+w9). Only two HLA‐DP MoAbs have been described.

3/ Satisfactory results, similar to those of LCT, were obtained with EIA using lymphoid cell lines as targets.

4/ Human MoAbs (12 in the Register) are satisfactory typing reagents. They could represent in the future a significant contribution to HLA typing with MoAbs.
Equine class II MHC antigens: identification of two sets of epitopes using anti‐human monoclonal antibodies
Authors: Monos D. S. , Wolf B. , Radka S. F. , Rifat S. , Donawick W. J. , Soma L. R. , Zmuewski C. M. , Kamoun M.
Published: October 2008

Six mouse and 13 rat monoclonal antibodies (mAb) recognizing HLA‐DR, DQ and DP antigens were used for the detection of cell surface class II MHC antigens of equine lymphocytes. The monoclonal antibodies were tested against peripheral blood lymphocytes (PBL) from a panel of thoroughbred horses, using two‐color fluorescence flow cytometry. Seven of these mAbs reacted with both surface immunoglobulin positive (sIg+) and surface immunoglobulin negative (sIg‐) lymphocytes. sIg+ cells stained consistently brighter than sIg− cells. The fluorescence pattern did not vary from donor to donor for each of the mAbs tested, except for SFR1‐MI.2, which reacted with a variable intensity with cells from 47 of 53 horses tested. Immunoprecipitation with mAb SFR1‐MI.2 and analysis by two‐dimensional electrophoresis demonstrated the presence of light and heavy chains equivalent to HLA class II α and β chains. Antibody N297 (DQ specific), previously shown to react with an epitope expressed on human B cells but not on mitogen‐induced T cells, reacted only with sIg+ cells in 42 of 53 horses tested. The lack of staining of horse sIg− cells with N297 may be due to a low or lack of expression of this determinant on these cells or to a weak cross‐reactivity of this antibody with equine antigens.
HLA‐DP antigens in patients with chronic autoimmune thrombocytopenia (AITP)
Authors: Mueller‐Eckhardt G. , Pawelec G. , Haas R. , Otto C. , Kiefel V. , ØSdum N. , Mueller‐Eckhardt C.
Published: October 2008

AITP, a disease with well‐defined autoimmune character, has been previously studied for a possible HLA association. However, no such association with antigens of the A, B, C or DR loci was found. As this does not exclude a possible association with HLA‐DP antigens, we have investigated 36 patients with AITP for DP w1, w2, w3, w4 and w5 by primed lymphocyte typing using locally derived as well as the original DP reagents as used in the 9th International Histocompatibility Workshop. Comparison of antigen frequencies with those of 254 healthy controls revealed an increased frequency of DPw5 in the patient group which, however, was not statistically significant. Other discrepancies were not observed.
Recurrent extended HLA haplotypes in children with selective IgA deficiency
Authors: Cuccia‐Belvedere M. , Monafo V. , Martineto M. , Plebani A. , Paoli F. De , Burgio G. R.
Published: October 2008

HLA supratypes as well as serum IgG, IgA and IgM levels were determined in 44 children and adolescents with severe IgA deficiency (serum IgA <5 rog/dl) and in first degree relatives. Frequencies of the HLA alleles B14, DR1, DQW1, C4A2 and C4B2 were significantly higher in the IgA‐deficjent patients than in the controls. The most recurrent haplorype among patients was B14, DR1 (p<10−4) preferentially associated with A33, A28 or A blank. The supratype B14, BfS, C4A2, C4B2, DR1, DQW1 was present in a 14‐fold higher frequency than in the controls, and strongly suggests the presence of a gene in the HLA region involved in the deficiency of IgA. The fact that this supratype was not always associated with IgA deficiency in the parents and that not all IgA‐deficient subjects had this supratype is discussed. Severe IgA deficiency was found in four mothers (two of the four mother‐child pairs shared the B14, DR1 haplorype); three other relatives (one father and two brothers) had partial IgA deficiency and did not have the B14, DR1, DQW1 haplotype.
HLA Bw57 and DR7 association with psoriasis vulgaris in south India
Authors: Pitchappan RM. , Koteeswaran A. , Kakkaniah V. N. , Manickasundari M. , Rajaram V. , Muthuveeralakshmi P. , Mahendran V. , Brahmajothibai V.
Published: October 2008

Eighty‐three south Indian patients with psoriasis vulgaris were studied for HLA antigen frequencies and compared with 77 controls studied simultaneously. HLA Bw57, a split of B17 was found elevated in the patients. The two sexes differed in their age‐at‐onset curves: females had a preponderance to early onset of the disease, while the males had late onset. Among these patients, major group 3, a Western Brachycephal Armenoid group, revealed the highest risk for B17 & Bw57 but not major group 2, a Mediterranean one.
Frequencies of HLA‐DP alleles in the four major types of leukaemia
Authors: Pawelec G. , Rehbein A. , And K. Schaudt , Busch F. W.
Published: October 2008

The frequencies of HLA‐DP alleles in 50 acute lymphocytic, 43 acute non‐lymphocytic, 50 chronic myelogenous and 51 chronic lymphocytic leukaemia patients were compared with 254 controls using primed lymphocyte typing. In CLL and ANLL there were significantly decreased frequencies of DPwl. Decreased DPwl and DPw3 was observed in ALL, but after correction for the number of comparisons made this was no longer significant. However, in ALL, even after correction, there were significantly increased frequencies of DPw2 and DPw5, whereas in ANLL and CLL the only significant increases were of DP‐blank, and in CML there were no positive or negative associations at all. These results suggest an influence of DP alleles in disease susceptibility and resistance in three of the four major types of leukaemia.
HLA association of anti‐IgA antibody production
Authors: Strothman R. A. , Sedestrom L. M. , Ball M. J. , Chen S. N.
Published: October 2008

We have HLA typed 46 unrelated IgA deficient blood donors in our region. A weak association to DR3 (RR = 2.07) was observed. However, owing to the heterogeneous nature of this group, we found DR7 may be associated with those who developed class‐specific anti‐IgA antibodies (RR = 2.94), whereas DR1 may be associated with those who did not (RR = 2.42).
Monoclonal antibody definition of the DRB3 allele, HLA‐Dw25
Authors: Fuggle S. V. , Carter C. , Morris P. J.
Published: October 2008

Monoclonal antibodies are powerful tools for analyzing HLA antigen polymorphism. We have investigated the serological and biochemical nature of the DRw52‐related antigen defined by the monoclonal antibody NDS10. A detailed analysis of the population distribution of NDS10 reactivity revealed that the epitope was present on a subpopulation of DRw52 positive cells. A distinct pattern of reactivity was found within DR3 individuals: all of the B18.DR3 cells were NDS10 positive, whereas the A1,B8,DR3 cells were negative. All of the DR5(w 11) cells and two of three DRwl2 cells reacted with NDS10. NDS10 reactivity with DRw6 was not restricted to either of the serologically defined subtypes; three of 17 DRwl3 and nine of 10 DRwl4 cells were NDS10 positive. NDS10 was unreactive with all of the DRw8 cells tested. Two‐dimensional gel analyses revealed that the NDS10 molecule precipitated from DR3, DR5(w11) and DRw6(w14) cell lines had an identical β chain profile. These data indicate that NDS10 recognises the Dw25 allele of the DRw52 complex.
RFLP analysis of DLA class I genes in the dog
Authors: Sarmiento U. M. , Storb R. F.
Published: October 2008

Human major histocompatibility complex (HLA) cDNA probes for class 1 genes HLA‐A,B and HLA‐E were used to analyze the Restriction Fragment Length Polymorphism (RFLP) of the class I region of the canine major histocompatibility complex (DLA) in 40 dogs. The Southern blot analysis demonstrated that the dog genome contains at least eight class I genes, including the canine homologues of HLA‐A,B and HLA‐E genes. The DNA polymorphism detected by the HLA‐B7 probe corresponded to the serologically defined DLA‐A allelic series. Restriction fragments that correlated with the DLA‐A2, ‐A7 and ‐A9 antigenic specificities were identified in PstI digests of genomic DNA. The RFLP analysis was particularly useful in genotyping dogs which were not clearly DLA‐A typable by serology. This technique can be used as a supplement to serotyping and as a genotyping tool for DLA antigenic specificities for which specific antisera are not available.
Time‐dependent variation of HLA‐antigen‐frequencies in fflV‐1‐infection (1983–1988)
Authors: Kuntz B. M. E. , Brüster H. Th.
Published: October 2008

In a 5‐year‐study of HLA‐phenotypes in 411 HIV‐1‐infected individuals, a progressive decrease of the formerly elevated frequency of HLA‐DR5 has been observed. HLA‐DR3 seems to have a protective effect. These results are discussed with respect to the mimicry‐hypothesis of HLA and disease associations. Further preliminary results indicate that HIV‐associated Kaposi's sarcoma could be associated with HLA‐A28, and therefore might be a different etiologic entity than HIV‐infection alone.
HLA Bw46 and DR9 associations in Graves’disease of Chinese patients are age‐ and sex‐related*
Authors: Yeo P. P. B. , Chan S. H. , Thai A. C. , Ng W. Y. , Lui K. F. , Wee G. B. , Tan S. H. , Lee B. W. , Wong H. B. , Cheah J. S.
Published: October 2008

The HLA‐A, ‐B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA‐DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves’disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1–19 yr, Pc = 0.0011, RR = 17.5. HLA associations (Bw46 and DR9) with Graves’disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1–19 yr (Bw46).
HLA linkage with familial vesicoureteral reflux and familial pelvi‐ureteric junction obstruction
Authors: Mackintosh P. , Almarhoos G. , Heath D. A.
Published: October 2008

The inheritance of HLA haplotypes has been looked at in a family with pelviureteric junction obstruction (PUJO) and two families with vesicoureteric reflux (VUR). The data have been combined with those of other reported families and lod scores calculated for both these urinary tract anomalies. There seems no doubt that VUR is linked to HLA whilst the case for PUJO is equivocal.
Association of maternal HLA haplotypes with recurrent spontaneous abortions
Authors: Christiansen O. B. , Riisom K. , Lauritsen J. G. , Grunnet N. , Jersild C.
Published: October 2008

Histocompatibility typing was done on 63 women with idiopathic, recurrent abortions (≥3 consecutive, spontaneous abortions; summarized abortion rate: 92.8%), 112 of their full siblings and 101 parents. The distribution of full sisters sharing 2, 1 and 0 of the probands' haplotypes diverged from expected Mendelian segregation (p < 0.05). Sisters sharing both the probands' haplotypes had an abortion rate of 59.1%, haploidentical sisters had an abortion rate of 25.0% whereas 6.3% of the pregnancies of the 0 haploidentical sisters had ended in miscarriage. The probands' HLA haplotypes included a significant (p < 0.02) excess of HLA‐A, B haplotypes which have previously been shown to exhibit features of positive linkage disequilibrium in Danes. Analysis of abortion rates among the probands and their siblings indicate that the idiopathic recurrent abortion syndrome and probably also the tendency to some sporadic abortions are inherited conditions determined by genes in the HLA region. The presented data may be compatible with an additive polygenic mode of inheritance with exclusive or predominant phenotypic expression in females controlled by an HLA linked spontaneous abortion subceptibility region (SASR).
Immune responses to the circumsporozoite protein of Plasmodium falciparum in relation to HLA‐DR type
Authors: Brown A. E. , Chandanayingyong D. , Fuggle S. V. , Webster H. K.
Published: October 2008

Associations between HLA‐DR/DQ phenotypes and immune responses to the circumsporozoite (CS) protein of the human malaria parasite, Plasmodium falciparum, were investigated in Thai adults. The frequency of DR and DQ types did not differ between 15 high antibody responders and 16 antibody non‐responders. Initial results which suggested that lymphocyte responses to a CS‐derived peptide (R32tet32) might be HLA‐DR associated were not confirmed by subsequent extension of the study. Thus, MHC restriction appears not to be a major factor in the frequently observed unresponsiveness of the immune system to the P. falciparum sporozoite. Based on these results, it is expected that MHC restriction will not be a major obstacle to the application of a malaria vaccine in outbred human populations.
Association of HLA antigens with progressive systemic sclerosis and morphea
Authors: Kühnl P. , Sibrowski W. , Boehm B. O. , Holzmann H. , Sollberg S.
Published: October 2008

The HLA phenotyype frequencies of 40 patients with progressive systemic sclerosis (PSS) and 42 patients with morphea (sclerodermia circumscripta) indicate a weak, HLA‐linked genetic predisposition of the affected individuals (70 female, 12 male). An “opposite” HLA Al, B8 (high immune response) vs A3, B7, DR2 (low immune response) constellation in PSS and morphea supports the clinical subdivision of scleroderma into these different nosological entities, and may serve as a differential diagnostic tool and prognostic marker.
HLA class I antigens in severe RSV bronchiolitis
Authors: Isaacs D. , Taylor C. J. , Ting A. , McMichael A. J.
Published: October 2008

Cytotoxic T‐lymphocytes (CTL) recognize virus‐infected cells in association with HLA class I antigens. There is strong evidence of the importance of CTL in respiratory syncytial virus (RSV) infections. We looked for but were unable to demonstrate an association between particular HLA class I antigens and severe RSV bronchiolitis in infants.
A DQA1 allele is strongly associated with idiopathic membranous nephropathy
Authors: Vaughan R. W. , Demaine A. G. , Welsh K. I.
Published: October 2008

The high molecular weight genomic DNA from 31 patients with idiopathic membranous nephropathy (IMN) has been digested with a restriction endonuclease Taq I, electrophoresed, blotted and hybridised with probes to the HLA‐DRB, ‐DQA, ‐DQB, ‐DPA and ‐DPB genes. The restriction endonuclease Msp I was also used with the HLA‐DPA and ‐DPB probes. The resulting restriction fragment length polymorphism (RFLP) has been analysed and compared with 55 controls treated in the same way. There was a significant increase in the DRB restriction fragments associated with HLA‐DR3 (Fisher's p = 0.011), in particular with a sub‐division of DR3 (Fisher's p = 0.0038). These results confirm at the DNA level serological correlations observed for IMN. A 4.5 Kb DQA RFLP was significantly raised in IMN patients (Fisher's p = 0.0002) and is proposed as a major disease susceptibility factor.
Association of RFLP of HLA class I genes with Chinese ankylosing spondylitis patients
Authors: Lin X. Y. , Wang Y. , Sun J. , Wang F. Q. , Ni L. Q. , Chang L. Y. , Chen S. S.
Published: October 2008

By serum typing, it is indicated that HLA B27 may be associated with the susceptibility to ankylosing spondylitis (AS). We analyzed DNA restriction fragment length polymorphism (RFLP) in 28 Chinese AS patients and 99 healthy controls, using a 1.4 Kb HLA class I cDNA probe. The results showed that the frequencies of the 8.1 Kb EcoRJ, 5.2 Kb EcoRI and 21.9 Kb Xbal fragments were found to be significantly increased in affected patients (P<0.0001, P = 0.0015, respectively), but that of 19.2 Kb XbaI fragment was decreased (P = 0.0021). The data suggest that AS may be a polygenic disease; furthermore, B27 and 8.1 Kb EcoRI band may be two different factors responsible for the susceptibility or just in linkage disequilibrium with the susceptible gene(s).
HLA‐DR and ‐DQ antigens in malnutrition‐related diabetes mellitus in Ethiopians: a clue to its etiology?
Authors: Abdulkadir J. , Worku Y. , Schheuder G. M. T. , D'Amaro J. , Vries R. R. P. de , Ottenhoff T. H. M.
Published: October 2008

Thirty Ethiopian malnutrition‐related diabetes mellitus (MRDM) patients were HLA typed and their HLA antigen frequencies were compared to those of 31 previously typed insulin‐dependent diabetes mellitus (IDDM) patients and to 84 controls from the same ethnic background. In comparison to controls, a striking association between MRDM and HLA‐DR3 (X2= 15.15, p = 0.0001) was observed, whereas the frequency of HLA‐DR4 was non‐significantly increased (RR = 1.72). The frequency of DR2, DQwl, and DQw6 was decreased among MRDM. In comparison to IDDM that is associated with both DR3 and DR4 in this population, MRDM showed no significant differences in HLA class II antigens frequencies. Therefore, the genetic basis of susceptibility to MRDM and IDMM in Ethiopia is at least partially identical.
Multiple sclerosis is associated with HLA‐DR2 antigen in Spain
Authors: Clerici N. , Hernández M. , Fernández M. , Rosique J. , Alvarez‐Cermeño J.
Published: October 2008

One hundred and twenty‐one Spanish multiple sclerosis patients were typed for HLA antigens. We found a significant increase of HLA‐DR2 (p<0.004) compared with local normal controls. We confirm similar findings in other Caucasian populations.
Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol‐anchored lymphocyte differentiation antigen ecto‐5′‐nucleotidase (CD73).
Authors: Thomson L. F. , Ruedi J. M. , Glass A. , Moldenhauer G. , Moller P. , Low M. G. , Klemens M. R. , Massaia M. , Lucas A. H.
Published: October 2008

Abstract: A panel of monoclonal antibodies to the 69 kDa glycosyl phosphatidylinositol anchored lymphocyte differentiation antigen ecto‐5′‐nucleotidase (ecto‐5′‐NT, CD73) was produced using highly purified human placental 5′‐NT as immunogen. Antibodies 1E9.28.1 and 7G2.2.11 inhibit soluble placental 5′‐NT activity and recognize lymphocyte CD73 in indirect immunofluorescence and immunoprecipitation assays. In addition, 1E9.28.1 induces vigorous T cell proliferation in the presence of submitogenic doses of phorbol myristate and F(ab′): goat anti‐mouse Ig. Both antibodies can be used to purify the three major forms of placental 5′‐NT by affinity chromatography. By two‐color immunofluorescence, CD73 was found to be expressed on 19±5% of CD3+, 11±4% of CD4+, 51±14% of CD8 +, 25±8% of CD28+, 15±5% of CD29 +, 27±7% of CD45RA+, and 70±6% of CD19+ lymphocytes. Within T cells, CD73 expression is restricted to the CD28+ subset. Thus, CD73 is found on subsets of both T and B lymphocytes, with the highest expression on B cells and CD8 + T cells. In sections of hyperplastic tonsil, CD73 expression is restricted to the small lymphocytes of the follicular mantle zone, a small subset of extrafollicular lymphocytes situated within the epithelium of the tonsillar crypt, and to follicular dendritic cells within the lower part of the “light‐zone.” CD73 is also detected on subsets of endothelial cells of capillaries and venules and the basal layer of non‐keratinizing squamous epithelium and transitional cell type mucosa of many tissues. Given the tissue distribution of CD73, along with its glycosyl phosphatidylinositol membrane anchoring and the observation that some CD73 antibodies are mitogenic, we propose that this interesting antigen may play a role in cell activation, lymphocyte homing, and/or cell adhesion.
A simple and rapid method for HLA‐DRB and ‐DQB typing by digestion of PCR‐amplified DNA with allele specific restriction endonucleases
Authors: Uryu N. , Maeda M. , Ota M. , Tsuji K. , Inoko H.
Published: October 2008

Abstract: The polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method, which we previously reported as an efficient and convenient typing technique for accurate definition of the HLA‐DQA1 and ‐DPB1 alleles, is now extended and applied to HLA‐DRB and ‐DQB typing. The second exon of the HLA‐DRB (B1 and B3 or B4) and DQB (B1 and B2) genes was selectively amplified from genomic DNAs of 70 HLA‐homozygous B cell lines by PCR. Amplified DNAs were digested with the restriction endonucleases, which can recognize allelic variations specific for HLA‐DR, ‐DQ, and ‐Dw allospecificities and then subjected to electrophoresis in polyacrylamide gel. Of DRB genes, FokI, HinfI, HhaI, HphI, KpnI and SacII were selected and the 20 different polymorphic patterns of the restriction fragments thus obtained were found to correlate with each HLA‐DR and ‐Dw type defined by serological and cellular typing. Of the DQB genes, FokI, HaellI, HhaI, RsaI and Sau3AI produced nine different polymorphic patterns of the restriction fragments, correlating with the HLA‐DQ and ‐Dw types. This PCR‐RFLP method provides a simple and rapid technique for accurate definition of the HLA‐DR, ‐DQ and ‐Dw types at the nucleotide level, eliminating the need for radioisotope as well as allele specific oligonucleotide probes.
Heterogeneity of HLA‐DR4 in Greeks including a unique DR4‐DQw2 association.
Authors: Awad J. , Ollier W. , Cutbush S. , Papasteriadis C. , Gupta A. , Carthy D. , McCloskey D. , Brown C. J. , Bokl K. , Fostizopoulos G. , Festenstein. H.
Published: October 2008

Abstract: It has been shown that Greek RA patients do not show an increased frequency of HLA‐DR4 compared with Greek controls. As only the Dw4 and Dwl4 subtypes of DR4 are implicated in RA, we have characterised DR4‐positive Greek RA patients and controls using serology, MLC typing and RFLP analysis to see whether the distribution of. DR4 subtypes or other HLA antigens associated with DR4 could account for these findings. In the 10 patients and 12 controls studied, Dw10 was common, being present in almost half the controls. Dw4 was not detected in the controls, but was present in three of the RA patients, indicating that there may be some relationship between Dw4 and RA in this population; Dw13 and Dw14 were also found, Dw15 was not detected. Eight of the subjects did not type as any of the HLA‐D antigens mentioned. Three controls had unusual DR4‐DQ associations, two having DR4‐DQw2 and one possessing DR4‐DQw4. Analysis of the TaqI DRB RFLP of the subjects showed that one control did not have the 6.1 kb band characteristic of DR4s. All these results indicate that DR4 is a heterogeneous antigen in this population and that several as yet undescribed variants of DR4 may be present.
HLA extended haplotypes in childhood and adult onset HLA—DR4‐associated arthropathies
Authors: Fraser P. JL , Stera S. , Larson M. G. , Marcus‐Bagley D. , Awdeh Z. , Glass D. N. , Alper G. A.
Published: October 2008

Abstract: : α HLA‐DR4 extended haplotypes have been established by family studies in children and adults with chronic arthritis, the children having polyarticular juvenile rheumatoid arthritis and the adults rheumatoid arthritis. These diseases are probably the same disorder presenting at different ages. The results demonstrate age‐related differences in the frequency of HLA‐DR4 extended haplotypes between the two groups of patients. The childhood onset was associated with the presence of the HLA‐B44, SC30, DR4 extended haplotype, whereas the adult form was more strongly associated with the HLA‐Bw62, SC33, DR4 haplotype. These results suggest that differences in the age at onset are influenced by the MHC in addition to the presence of the HLA DR4 gene itself.
HLA‐associated non‐responsiveness to Hepatitis B vaccine
Authors: Varla‐Laftnerioti M. , Papanicolaou M. , Spyropoulou M. , Vallindra H. , Tsiroyianni P. , Tassopoulos N. , Kapasouri H. , Stavropoulos‐Giokas C.
Published: October 2008

Abstract: : HLA‐A,B,DR antigens of two groups, one of normal individuals (N−= 31) and another of CRF (Chronic Renal Failure) patients (K−= 37), who did not develop anti‐HBs protective antibodies after Hepatitis B (HB) vaccination, were compared, respectively, to the HLA antigens of two corresponding control groups (N+=52, K+=49), who responded to the vaccine. A statistically significant difference (Pc < 0.02) in the frequency of HLA‐DR3 was observed between responders and non‐responders. An increased frequency of HLA‐A1 and HLA‐B8 in N− as well as of HLA‐A1 and HLA‐B35 in K− was also noticed, but this was not of statistical significance. As these antigens have been associated to both HBs antigenemia as well as chronic active hepatitis, we suggest that these genes or other genes in linkage to those may suppress the response to HBV vaccination while, in parallel, they may predispose to an autoimmune course of Hepatitis.
HLA‐DR, DQ antigens in North American Caucasians
Authors: Lee T. D. , Lee G. , Zhao T. M.
Published: October 2008

Abstract: : HLA‐DR,DQ specificities are determined by serological methods in 2,586 North American Caucasians. Antigen frequency, gene frequency and haplotype frequency are computed for each phenotype observed. The DR. and DQ loci antigen distributions are well‐fitted to a Hardy‐Weinberg equilibrium (p>0.25 for DR locus, p>0.10 for DQ locus). All World Health Organization (WHO) recognized HLA‐DR,DQ specificities were found except HLA‐DRwl8, which has been identified only in the black population. DR and DQ linkage disequilibria among recently defined splits is observed. The following DR and DQ associations are found: DR1 and DQw5; DR4 and DQw7, DQw8; DR7 and DQw2, DQw9; DR8 and DQw4, DQw6, DQw7; DR9 and DQw2, DQw9; DRw10 and DQw5; DRw11 and DQw6, DQw7; DRw12 and DQw5, DQw7; DRw13 and DQw6, DQw7; DRw14 and DQw5, DQW7; DRw15 and DQw6, DQw7; DRw16 and DQw5; DRw17 and DQw2. In this large study population, the following unusual DR and DQ associations are found: DR4, DQw2; DR4, DQw1; DR1, DQw7; DR7, DQw5; DRwl7, DQw6; and other unusual haplotype phenotypes containing DRX, DQX.
HLA‐DP, ‐DQ and ‐DR RFLP types in South Indian insulin‐dependent diabetes mellitus patients
Authors: Easteal Simon , Viswanathan M. , Sarjeantson Susan W.
Published: October 2008

Abstract: : The frequencies of HLA‐DP, DQ and DR RFLP types are compared between insulin‐dependent diabetes mellitus (IDDM) patients and healthy controls in the South Indian population. There are no significant differences in the frequencies of any of the DPA.DPB haplotypes, when allowance is made for multiple comparisons. The individual frequencies of two novel alleles, designated “DPA*B” and “DPB*B”, however, are significantly higher in controls than in patients, suggesting that these alleles are protective against IDDM. A negative association with DRwl5 (DR2).Dwl2 is also observed. The positive association with DPw3/6 RFLPs previously observed in White Australians is not present in South Indians. This difference may be due either to undetected heterogeneity within allelic classes or to different linkage disequilibrium patterns between the populations.
Characterization of two hybrid C4 allotypes (C4A*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses
Authors: McLean Robert H. , Bias Wilma B. , Giles Carolyn , Yn C. Y. , Campbell R. Duncan
Published: October 2008

Abstract: : Informative pedigree analysis of two rare C4 allotypes is reported. One proband was C4A deficient as a consequence of having one haplotype with a deleted C4A gene, and the second haplotype with two C4B genes ‐ one encoding the common C4B*1 and one encoding a unique hybrid gene product C4B*3. C4B*3 had approximately normal C4B hemolytic activity, a single α‐chain of MR 94,000 by SDS‐PAGE but was positive for Rg:1,2 by hemagglutination inhibition (HAI) and for Rg.1 by Western blotting. The hybrid nature was confirmed by RFLP analysis with a Rg:1‐associated fragment by Eco0 109 digestion but no C4A‐associated fragments by NlaIV digestion were identified. A gene conversion at Locus I which included just the C4 isotype region could explain the structure of C4B*3. The second pedigree had a Rodgers negative C4A*12 allotype. This C4A gene, which segregated with a single 7.0 kb Taql fragment, encoded a C4A α‐chain, which was negative for Rg.1 epitope. The affected haplotype lacked the Rg:1‐associated fragment by Eco0109 digestion yet had the C4A specific NlaIV digestion fragment. These studies successfully employed RFLP analyses to confirm serologic and electrophoretic observations.
Differential expression and regulation of the human CD8α and CD8β chains
Authors: Terry L A. , DiSanto J. P. , Small T. N. , Flomenberg N.
Published: October 2008

Abstract: The CD8 glycoprotein is expressed by thymocytes, mature T cells and natural killer (NK) cells and has been implicated in the recognition of monomorphic determinants on major histocompatibility complex (MHC) Class I antigens, and in signal transduction during the course of T‐cell activation. Both human and rodent CD8 antigens are comprised of two distinct polypeptide chains, α and β. The majority of monoclonal antibodies (mAb) reactive with the human CD8 antigen bind the CD8α chain, while a single mAb, T8/2T8–5H7, has been identified which binds to the CD8 α/β heterodimer. While the two chains of CD8 have been presumed to be coordinately expressed in normal T cells, this is not always the case. Northern blot analysis of a panel of T‐cell leukemias and normal cells demonstrate that CD8α and CD8β are not invariably co‐transcribed and phenotypic analysis of fresh and interleukin 2 (IL‐2) expanded peripheral blood mononuclear cells (PBMC) confirm that the CD8α and CD8β chains are differentially expressed at the cell surface. Four distinct subpopulations of CD8 + cells have been identified based on the expression of CD8 α/α or CD8 α/β complexes: (1) T‐cell receptor (TcR) αβ+ T cells which are CD8 α+/β+ (2) TcR αβ+ T cells which are CD8 α+/β‐; (3) TcR γδ+ T cells which are CD8 α+/β‐ and (4) natural killer (NK) cells which are CD8 α+/β‐. We also demonstrate the down‐regulation of the CD8 α/β heterodimers from the surface of a CD8 + T‐cell clone following treatment with phorbol myristate acetate (PMA) while CD8 α/α homodimers remain on the cell surface. This observation demonstrates that a) a CD8+ T‐cell clone can express both CD8 α/α homodimers and CD8 α/β heterodimers and b) these two complexes do not have identical biological properties. Together, these data suggest that CD8 α/α and CD8 α/β dimers may not subserve identical functions. The differential contribution of these two CD8 complexes should be considered in models of T‐cell‐mediated cytotoxicity and T‐cell activation.
Identification of a CD4 homologue in the cat
Authors: Ackley C. O. , Hoover L A. , Cooper M. D.
Published: October 2008

Abstract: : Monoclonal antibody, Fel 7, produced against cat T cells, was found to react with a single‐chain glycoprotein of Mr 65,000 present on a majority of the thymocytes, 40% of lymph node cells, 15% of splenocytes and 25% of blood mononuclear cells. Using a previously reported antibody that recognizes the feline CD8 antigen, approximately 65% of cat thymocytes were shown to express both the Fel 7 and fCD8 antigens, while 14% and 6% expressed either the Fel 7 or the fCD8 determinant respectively. The Fel 7 and fCD8 antigens were expressed by mutually‐exclusive subpopulations of peripheral T cells, and not by B cells, macrophages or other types of blood cells. Expression of the Fel 7 antigen was down‐regulated and the molecule was phosphorylated when T cells were stimulated with phorbol ester, while the expression of the fCD8 antigen was unaffected by this treatment. The addition of soluble Fel 7 antibodies efficiently blocked Con A‐induced proliferation of T cells in a dose‐dependent manner. The data suggest that the mAb Fel 7 identifies a feline CD4 homologue, providing an important reagent for the study of normal and abnormal T cell development in cats.
Conserved and variable structures in HLA class I molecules: a review
Authors: Colombani J.
Published: October 2008

Abstract: Amino acid sequences and structural data on HLA class I molecules are now available, making possible a comparison of the serological and structural definitions of allelic series.

1) A hierarchy of differences between molecules is observed. Certain molecules show a low level of differences (1.2% of amino acids) and represent variants of original molecules. Other molecules are recombinants derived from two parent molecules (2.5% difference). Original molecules from an allelic series have a higher level of difference (7.6.%). Maximum differences (13.5%) are observed between products from different loci. Serologically related specificities (cross‐reacting groups) show a relatively low level of difference (6.4%).

2) In most specificities an exclusive residue can be considered as responsible for the formation of a serologically recognized determinant. Certain specificities do not have an exclusive residue; they can then be characterized either by a unique determinant made by the association of several non‐exclusive residues, or by an unique association of several non‐exclusive (shared) determinants. There is a significant correlation between the absence of an exclusive residue and the absence of monoclonal antibodies recognizing certain specificities. This suggests two kinds of definition of serological specificities, either by a single exclusive determinant (monotopic recognition) or by several shared determinants (polytopic recognition). Private and public specificities are recognized at the structural level. T‐cell receptor (TCR) recognizes either a xenogeneic peptide in the context of self HLA molecules (restricted CTL [Cytotoxic T Lymphocyte]), or allogeneic HLA molecules. Determinants recognized by CTL (restricted or allogeneic) on HLA molecules have been identified. It is not possible to ascertain whether determinants recognized by antibodies and TCRs are identical, but they are probably very similar.

3) HLA class I molecule is made of 75% conserved residues (mostly in the α3 and β2‐m domains) and of 25% variable residues (mostly in the α1+α2 domains). Conserved residues maintain the general shape of the molecule, its outward orientation on the cell membrane, its association with T cells CD8 molecule, and the structure of the peptide binding site, a groove at the top of molecule. Variable residues are responsible for the capacity of each molecule to bind and to present a large number of different peptides to the TCR. Each molecule carries several (3–10?) variable sites; certain are localized into the groove and are recognition sites while others, more exposed on the surface of the molecule, are sites recognized by TCRs and antibodies. Both conserved and variable regions are necessary to the function of the HLA molecule.
HLA‐DP antigens in patients with alopecia areata
Authors: Ødum N. , Morling N. , Georgsen J. , Jakobsen B. K. , Frentz G. , Jensen G. F. , Fugger L. , Svejgaard A.
Published: October 2008

Abstract: The distribution of HLA‐DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA‐DP typing for DPwl through w6 and the local specificity, CDP HEI, was performed using the primed lymphocyte typing (PLT) technique.

The frequencies of DPw4 were 92.9% in AA patients and 71.3% in controls (relative risk, RR = 5.1, p = 0.0019 and p < 0.03 when corrected). DPwl was decreased to 4.9% in patients compared to 14.9% in controls, but the difference was not statistically significant. The frequency of DR4 was 48.8% compared to 31.9% in controls (RR = 2.0) whereas the frequency of DR5 did not differ from that in controls.

DPw4 was not associated (in linkage disequilibrium) with DR4 or DR5 in patients or controls. Thus, in AA the association with DP and DR are independent of each other. However, individuals with both the DPw4 and DR4 alleles are at increased risk for AA, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to AA.
Activation of CD8+ T cells by allogeneic class II‐deficient B‐cell lines derived from patients with bare lymphocyte syndrome
Authors: Jin Z. , Yang S. Y.
Published: October 2008

Abstract: The major histocompatibility complex (MHC) class II antigens (Ags) are known to carry the major stimulating determinants of the primary mixed lymphocyte reactions (MLR). We investigated the mechanism of generating HLA class I‐directed alloreactive T‐cells in primary MLR. With the use of class II‐deficient EBV‐transformed B‐lymphoblastoid cell lines (B‐LCLs) derived from patients with bare lymphocyte syndrome (BLS), we have demonstrated in the present study that class I disparity alone can trigger primary MLR in the absence of exogenous IL‐2. The CD8+ T cells were primary MLR‐responsive cells, and the CD4+ T cells seem to play no role in primary MLR when class II alloantigens are not involved in stimulation. Addition of autologous macrophages did not influence the primary MLR response. The primary MLR was completely blocked by anti‐class I or anti‐CD8 antibodies but not by anti‐class II or anti‐CD4 antibodies. The MLC‐generated CD8+ T cells exhibited cytolytic activity as well as proliferative responses. The proliferative response of the CD8+ T cells was specifically directed against class I antigens, demonstrated by proliferatlire assays; and the helper‐independent CD8+. T cells were generated only when the activation of CD4+ T cells did not occur. This observation suggests that functional recruitment of T‐cell receptor (TCR) repertoire is under active regulation, and the suppression of CD8+ T‐cell helper recruitment appears to be dictated by the CD4+ T‐cell subset. Further analysis of the primed T‐cell specificities showed that alloreactivity of the CD8+ T cells was mostly accounted for by the HLA‐B Ags. The higher alloreactivity against the HLA‐B Ags may probably be due to the high frequency of HLA‐B‐directed T‐cell clones, and the high frequency is probably due to their higher sequence variability in HLA‐B than in the HLA‐A and HLA‐C Ags.
DNA polymorphism of major histocompatibility complex class II and class III genes in systemic lupus erythematosus
Authors: So A. K L. , Fielder A H. L. , Warner C. A. , Isenberg D. A. , Batchelor J. R. , Walport M. J.
Published: October 2008

Abstract: We investigated the Taq I digested DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA‐DRB, ‐DQA, and the class III genes: C4 and 21‐hydroxylase(CYP21) in 56 caucasoid patients with systemic lupus erythematosus (SLE) and 62 control subjects in order to define the molecular variation of these genes and their association with SLE. The results showed that the gene frequencies of both HLA‐DR2 and ‐DR3 were significantly increased in the SLE population compared to normal subjects (DR2: 21.4% vs 10.7%; χ2= 4.5. DR3: 29.6% vs 13.3%; χ2= 8.3). A high frequency of C4A and CYP21A gene deletions was also found in SLE patients (SLE 52%, normals 24%). All of 22 SLE patients, and 12 of 15 normal subjects who had C4A and CYP21A gene deletions had a 10.0kb Taq 1 DRB RFLP attributable to the presence of HLA‐DR3. Family studies showed linkage of C4A/CYP21A deletions with HLA‐B8 and ‐DR3, and confirmed the previously demonstrated association of the HLA‐B8, DR3, C4A*Q0, C4*B1, Bf*S, C2*C haplotype with SLE. Deletions affecting the C4A and CYP21A genes were the commonest cause of C4A null alleles in SLE. No strong association between C4 null phenotype or C4 gene deletion, as determined by RFLP, was observed in patients who possessed DR2.
Characterization of a porcine CD1‐specific mAb that distinguishes CD4/CD8 double‐positive thymic from peripheral T lymphocytes
Authors: Pescovitz M. D. , Hsu Su‐Ming , Katz S. I. , Lunney J. K. , Shimada S. , Sachs D. H.
Published: October 2008

Abstract: Porcine peripheral T‐cells bear CD4 and CD8 cell surface antigens that distinguish helper from cytotoxic T‐cells. In distinction from what has been found in other species, a large percentage of peripheral T‐cells simultaneously express both CD4 and CD8. Monoclonal antibody 76‐7‐4 was found to stain all cortical and 7 ± 3% of medullary thymocytes, Ia+ epidermal cells (i.e. Langerhans cells), no peripheral T‐cells and 50% of peripheral B‐cells. The antigen detected appears analogous to human CD1. All cortical thymocytes were also stained with CD4 and CD8 mAb. Since 76‐7‐4 did not stain peripheral T‐cells, we conclude that CD4/CD8 dual‐expressing peripheral T‐cells are not simply immature thymic emigrants.
T‐cell receptor β‐chain DNA polymorphism frequencies in healthy HLA‐DR homozygotes
Authors: Charmley Patrick , Concannon Patrick , Gatti Richard A.
Published: October 2008

Abstract: In view of numerous recent reports of T‐cell receptor (TCR) β‐chain/disease associations with HLA‐associated diseases, we tested the possibilities that associations might exist directly between these two gene complexes at the level of the germline DNA. We determined frequencies of five TCR‐β DNA polymorphisms in 33 HLA‐DR2/2 homozygotes, 29 HLA‐DR3/3 homozygotes and 42 HLA‐DR4/4 homozygotes. The control population (n = 74) was chosen without “bias toward” their HLA‐DR genes. We selected DR2, DR3 and DR4 homozygotes because they have been the most frequently involved in HLA‐DR associated diseases. Our results indicate that the recent reports in the literature of TCR‐β/ disease associations can not be explained by a significantly different distribution of TCR‐β genes in HLA‐DR2+, ‐DR3+, or ‐DR4+ subpopulations. Our results also suggest that if co‐evolution between TCR‐β and MHC haplotypes does exist, the selective pressures in recent generations have not been strong enough to significantly alter the germline TCR‐β gene frequencies in HLA‐DR2+, ‐DR3+, or ‐DR4+ subpopulations.
Applicability of HLA‐DQB oligonucleotide typing for the TA10 and 2B3 specificities in routine HLA typing
Authors: Vijverberg K. , Schreuder G. M. Th. , Kenter M. J. H. , Naipal A M. , van Rood J. J. , Giphart M. J.
Published: October 2008

Abstract: Our group recently developed oligonucleotide probes associated to the TA10 and 2B3 specificities (1). Unambiguous typings were observed in a panel of homozygous typing cells and a family, using 32P‐end labeled probes and PCR‐amplified DNA (DQB exon 2). To investigate whether these TA10 and 2B3 associated oligonucleotides could be used in routine HLA‐typing we extended the study to a panel of healthy, unrelated individuals. When TA10 and 2B3 typings by oligonucleotides were compared with those obtained in routine serology a complete correlation was observed for TA10. A discrepancy was seen for 2B3 typing in material obtained from DQw5‐ (and possibly DQw4)‐positive individuals which could be explained by the CYNAP (cytotoxicity‐negative, absorption‐positive) phenomenon, using the IIB3 monoclonal antibody in routine tissue typing. Our results suggest that HLA‐DQB oligonucleotide typing for TA10 and 2B3 is an accurate and reliable method and can be used effectively in routine HLA typing.
The effect of parental and maternal‐fetal histocompatibility at MHC on sex ratio in offspring
Authors: Astolfi P. , Martinetti M. , Gigli‐Berzolari F. , Cuccia M.
Published: October 2008

Abstract: The secondary sex ratio (male births of total births) variation was investigated as a function of MHC antigens. Previous studies have indicated that at conception male zygotes are more frequent than female ones and abortions of male fetuses prevail. The present investigation addresses the question whether the histocompatibility relationships either between parents or between mother and offsprings may favor or hinder the outcome of pregnancy: particular combinations may cause distortions in the sex ratio. The results of the analysis of a sample of fertile families, demonstrate that, in first panties, female births are favored when parents share antigens at both HLA‐A and ‐B loci (S.R. = 0.389), and mothers and fetuses share antigens at the HLA‐B locus (S.R. = 0.222). The lack of antigens shared by parents at the three loci HLA‐A, ‐B and ‐DR increases first male births (S.R. = 0.696). In the case of fetal maternal histocompatibility at DR locus only a slight, non‐significant, increase in male first births (S.R. = 0.667) was observed. The effect of histocompatibility at HLA‐B locus alone requires further investigation in order to assess the possible selective effect against male histocompatible embryos.