bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of HLA‐D gene products in the normal and coeliac small bowel
Authors: Kelly J. , Weir D. G. , Feighery C.
Published: October 2008

Monoclonal antibodies to monomorphic determinants of the MHC class II region products, HLA‐DR, DP and DQ were used to investigate their expression on cells of the normal and coeliac (both treated and untreated) small bowel. HLA‐DR antigens showed a characteristic distribution in the normal small bowel: epithelial cells in the apical portions of the villi stained heavily, and this staining decreased in intensity towards the villous base. The crypt epithelial cells were clearly unstained. Stellate cells within the lamina propria were also HLA‐DR positive. HLA‐DP antigens showed a similar distribution, although the intensity of staining was less than that seen with HLA‐DR. HLA‐DQ antigens were absent from epithelial cells and were confined solely to cells within the lamina propria. In untreated coeliac disease, the intensities of both HLA‐DR and HLA‐DP were increased, and in addition a more extensive distribution of these antigens was observed. In addition to occurring on the surface epithelial cells, DR and DP antigens were now present on crypt epithelial cells. Despite this change in expression of DR and DP antigens, the distribution of HLA‐DQ was essentially unaltered from that of the normal small bowel. The findings in treated coeliac disease were intermediate between those in the normal and untreated coeliac small bowel. The differential expression of class II antigens by normal and diseased small bowel epithelium which has been demonstrated may have implications for interactions of these cells with cells of the immune system.
Restriction fragment length polymorphism (RFLP) of a “new” HLA‐DP specificity, CDP‐HEI
Authors: Hyldig‐Nielsen J. J. , ØDum N. , Morling N. , Svejgaard A.
Published: October 2008

Southern blotting with a DPβ cDNA probe of MspI digested DNA from 83 healthy unrelated individuals revealed a 1.8 kb fragment present in all four individuals (and no others) possessing the newly determined DP specificity, CDP‐HEI.
Expression of polymorphic B‐cell antigens on human kidneys
Authors: Hancock R. J. T. , Harvey J. , Evans P. R. , Hodges E. , Molnar J. , Martin A. , Lewis L. , Cohen B. , Laundy G. , MacIver A. G. , Bradley B. A.
Published: October 2008

We have examined the expression on a panel of 22 human kidneys of polymorphic B‐cell determinants recognized by mouse monoclonal antibodies. Monoclonal antibodies from a mouse immunized with an antigenic preparation from a DR4 positive B‐cell line reacted preferentially with kidneys from DR4 positive donors (p <0.005), and the pattern of reactivity with kidney tissues was similar to that of antibodies to monomorphic determinants of class II. However, these antibodies did not show clear specificity for DR4 on lymphocytes in standard serological analyses. These results provide evidence for the expression of polymorphic class II determinants on human kidneys. Reasons for the differences in the apparent specificities of the monoclonal antibodies when tested on kidney sections, and lymphocytes are discussed.
Gamma interferon induces detectable serological and functional expression of DR and DP but not DQ antigens on cultured amniotic fluid cells
Authors: Maurer D. H. , Callaway C. , Sorkin S. , Pollack M. S.
Published: October 2008

Cultured amniotic fluid cells, which are used for HLA typing studies for the prenatal diagnosis of HLA linked diseases and for prenatal determination of paternity, usually contain mixtures of fibroblastic and epithelioid cells. Cells of both types lack constitutive expression of HLA class II antigens, but these can be induced by pretreatment with gamma interferon. Both serological and functional studies indicate that detectable levels of DR and DP but not DQ antigens can be thereby induced. DR and DP cannot, however, be induced on chorionic villus cells.
Recombination within the class III region by a double cross over event
Authors: Rose M. , Menzel G. R. , Geserick G. , Doxiadis G. , Grosse‐Wilde H. , Mukaida M. , Rackwitz A.
Published: October 2008

Analysis of class I, class II, and class III gene products of the human MHC in a Caucasoid family with four children gave evidence for a double crossing over event in monozygotic twins between the C2, Bf/C4A, C4B gene loci. In view of the small genetic distance between C2 and C4, a point mutation within the Bf locus must be considered alternatively.
HLA‐DR expression by adrenocortical cells of the zona reticularis: structural and allotypic characterization
Authors: Khoury E. L. , Berline J. W.
Published: October 2008

We previously reported that human adrenocortical cells in the zona reticularis of normal glands express antigenic determinants recognized by HLA‐DR monoclonal antibodies (MoAbs). In the present study, it is shown that these adrenocortical HLA‐DR determinants are present on glycoproteins having similar structural characteristics, regarding subunit composition and molecular weight, to those of HLA‐DR molecules present on immunocomponent cells. Furthermore, adrenocortical HLA‐DR molecules include serologically‐defined genetically‐appropriate allotypic specificities, detectable by immunostainings with both HLA‐DR human alloantisera and MoAbs against polymorphic HLA‐DR determinants. The anding of a normal expression of HLA‐DR antigens by these highly differentiated and biosynthetically active endocrine cells gives support to the notion that MHC class II molecules may perform biological functions in addition to those related to the immune response.
HLA‐DQw3.1 and DQw3.2 associated exon polymorphisms detected by oligonucleotide probes
Authors: Markussen G. , Rosnningen K. S. , Paulsen G. , Gaudernack G. , Sollid L. M. , Thorsby E.
Published: October 2008

HLA class II polymorphisms have been analyzed on the genomic level by two oligonucleotide probes corresponding to the DNA sequence coding for the amino acids 23–30 in the first domain of the beta chain of DQw3.1 and DQw3.2. Specific hybridization to single endonuclease fragments of DNA from some HLA homozygous cells was detected. Here we report the distribution of these DNA exon sequences among different DQ alleles, and demonstrate that the probes may be used to type for DQw3.1 and DQw3.2 respectively.
HLA‐linked susceptibility to rheumatoid arthritis in North India
Authors: Mehra N. K. , Kaul R. , Taneja V. , Chaudhuri T. K. , Jhinghan B. , Malaviya A. N.
Published: October 2008

Nine multiplex RA families of North Indian origin were tissue typed to determine the segregation of parental haplotypes among sibs. The assortment of haplotypes in 18 affected sibs was not random, with seven sib pairs being HLA identical and two haploidentical with the proband (P = 0.0007). HLA‐DR4 occurred in eight out of nine probands (88.8%) and in 11 out of 13 familial RA subjects (84.6%).
MHC classes I, II, III antigens study in 70 insulin‐dependent diabetics with associated auto‐immune diseases
Authors: Gony J. , Vexiau P. , Lhomme C. , Marcelli A. , Poirier J. C. , Bochu V. , Cathelineau G. , Assan R. , Deschamps I. , Hors J.
Published: October 2008

Seventy IDDM patients (insulin‐dependent diabetics), 48 females and 22 males, most of them adults at the onset of diabetes, and suffering from at least one other associated autoimmune manifestation (AAM) were studied for HLAA, B, C, DR markers and Bf, C4 complement components. Comparisons were made with 108 normal controls and a series of 287 IDDM patients with juvenile onset (under 25 years) and no patent other autoimmune disease. The increase in frequency of HLA‐B8 among IDDM patients with AAM was confirmed (36% versus 20% in controls) (p<0.04). The frequency of DR4 among diabetics with AAM (33%) was not significantly different from the normal frequency (27%), and the allelic combination DR3/4 was found in only 13% of IDDM with AAM. Corresponding frequencies in patients with IDDM alone were 66% for DR4 and 34% for DR3/4 (p < 10‐6 and 10‐3 respectively). These results confirm the heterogeneity of IDDM and support, by genetic arguments, the concept of overlapping entities. The hypothesis of a common background of autoimmunity associated with B8 DR3 can be postulated, while the organ specific target process should be associated with various DR alleles.
HLA‐DP antigens are involved in the susceptibility to multiple sclerosis
Authors: ØDum N. , Hyldig‐Nielsen J. J. , Morling N. , Sandberg‐Wollheim M. , Platz P. , Svejgaard A.
Published: October 2008

Forty‐five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA‐DP using Primed Lymphocyte Typing. Thirty‐nine MS‐patients and 63 controls were also DNA‐typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA‐DP and ‐DR genes. The frequencies of DPw4 were 93.3% in MS patients and 72.3% in controls (relative risk, RR = 5.4, p = 0.0014). The DR2 antigen was present in 75.5% of the patients and in 33.7% of the controls (RR = 6.1, p < 10‐6). DPw4 was not associated (i.e., was not in linkage disequilibrium) with DR2 in patients or controls. Thus, in MS the associations with DP and DR are independent of each other. However, the combined presence of DPw4 and DR2 gave a significantly higher risk than each antigen alone, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to MS.
Study of HLA antigens in systemic lupus erythematosus in the French West Indies
Authors: Monplaisir N. , Valette I. , Pierre‐Louis S. , Yoyo M. , Sobesky G. , Verpré F. C. , Quisi D. , Arfi S. , Gervaise G. , Gabriel J. M. , Artax H. , Raffoux C.
Published: October 2008

As incidence of SLE is high in Blacks, we studied HLA and SLE associations in the French West Indies, whose population is racially mixed. Forty‐seven coloured SLE patients have been typed in HLA A, B, C and DR. We observed B8 association in nearly all of the studies. B15 association, more frequent in Caucasians, was found, also B53 association, a Black variant of B5 more frequent in Blacks. We did not find any class II association.
Association and linkage studies of immunoglobulin heavy chain allotypes in inflammatory bowel disease
Authors: Gudjonsson H. , Schanfield M. S. , Albertini R. J. , McAuliffe T. L. , Beeken W. L. , Krawitt E. L.
Published: October 2008

Inflammatory bowel disease is a familial disorder of unknown etiology, characterized by a variety of immunological abnormalities for which there are no proven genetic markers. Studies of immunoglobulin heavy chain and light chain allotypes were undertaken in 89 patients with Crohn's disease and in 18 families with ulcerative colitis or Crohn's disease in at least two first‐degree relatives, to search for association and/or linkage between a postulated disease susceptibility locus and an immunoglobulin allotype locus. No evidence of association or linkage with a specific immunoglobulin allotype was found.
Increased frequency of HLA‐A3 in subjects with sporadic porphyria cutanea tarda
Authors: Edwards C. Q. , Griffen L. M. , Kushner J. P.
Published: October 2008

The HLA‐A3 alloantigen, usually associated with the heraochromatosis gene, was detected in 12 of 18 patients (67%) with sporadic porphyria cutanea tarda but in only 23 per cent of 328 normal subjects (p = 0.0006). This difference remained significant after correcting for the number of HLA‐A locus antigens tested (p = 0.025). These results suggest that an HLA‐linked hemochromatosis allele is present and may account for the iron abnormalities in many patients with sporadic porphyria cutanea tarda.
Study of cis and trans interactions between extended HLA‐haplotypes in insulin‐dependent diabetes
Authors: Deschamps I. , Marcelli‐Barge A. , Lallemand N. , Poirier J. C. , Bochu V. , Prévost P. , Busson A. , Massét M. , Lestradet H. , Hors J.
Published: October 2008

From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin‐dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. In the “cis” situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. Two haplotypes, S31 associated with DR2 or DR5 and F31 associated with DRw6 or DR7 had a protective effect.

In the “trans” situation (opposite haplotype) the large excess of DR3/DR4 hetero‐zygotes was not the only distortion observed. An excess of DR1 (57%) and of C4BQ0 (40%) was noted among non DR3, non DR4 haplotypes in diabetics compared to normal individuals (26% and 23%, respectively, p<0.01, 0.05). Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. The protective antigens HLA DR2, DR5 and DR7 seemed not to be distributed randomly: their putative protective effect was not observed in the case of combination with DR1 or a B18, DR3 haplotype. DR2 was never found homozygous or combined with DR5.

These results suggest that susceptibility to IDDM is generated by both cis and trans interactions between genes or gene products of the HLA region.
Expression of class I ‐ like alloantigens on leukemic cells is not correlated with the amount of HLA‐A, B, C molecules
Authors: Peruccio D. , Crepaldi T. , Castagnoli C. , Lecchi M. , Resegotti L. , Miniero R. , Guerra M.G. , Richiardi P.
Published: October 2008

The expression of class I‐like allospecificities on leukemic blasts is not correlated to the amount of HLA‐A, B, C molecules, as measured with MoAb W6/32 and IIP, nor with the quantitative expression of HLA‐A molecules evaluated by absorption studies.
Cyclosporin A mediated immunosuppression in vitro: effect on high affinity interleukin‐2 receptor expression and ‐turnover
Authors: Povlsen J. V. , Møller B. K. , Christiansen B. S. , Petersen C. Munck
Published: October 2008

The effect of in vitro administration of Cyclosporin A (CsA) during mitogen, antigen and alloantigen activation of human T‐lymphocytes on high affinity interleukin‐2 (IL‐2) receptor expression and ‐turnover and IL‐2 production was investigated. The presence of CsA reduced 3H‐thymidine incorporation and binding of radiolabeled human recombinant (ala125) IL‐2 to high‐affinity receptors in a dose‐dependent fashion, although a pronounced inter‐ and intra‐individual variation in sensitivity to CsA mediated immunosuppression was observed. Maximum inhibition was obtained when antigen and CsA were added to culture medium simultaneously. Preincubation with CsA did not influence the response. Although the number of IL‐2 receptors was reduced, the turnover of the remaining high affinity IL‐2 receptors on CsA treated cells was unaffected. Thus, binding, internalization and degradation were qualitatively unaltered by CsA administration. Finally, T cell activation in the presence of CsA reduced radioimmuno detectable IL‐2 in cell culture supematants to about 20%. CsA, added during antigen activation, reduced the number of Tac antigen presenting cells, but anti‐Tac was unable to detect variations in the expression of high affinity IL‐2 receptors. The present data indicate that CsA mediates immunosuppression by affecting early events during T‐cell activation, and that variations in high affinity IL‐2 receptor expression and IL‐2 production are secondary to this affection.
Co‐segregation of HLA and rheumatoid arthritis in multicase families
Authors: Silman A. , Hennessy E. , Ditri M. , Ollier W.
Published: October 2008

Inheritance of parental HLA haplotypes was examined in the offspring of 95 multicase rheumatoid arthritis (RA) families. Overall, in these families there was no evidence of preferential transmission of one parental haplotype, although this might have been expected given the loading of these families with RA cases. However, there was a difference in inheritance when the affected and non‐affected offspring were compared. A co‐segregation analysis showed that the inheritance of parental HLA haplotypes was different between the affected and the unaffected offspring. Unlike a previous report, no difference was demonstrated in this study between the offspring of affected and non‐affected parents. Similarly, the affected offspring of HLA DR4 heterozygote parents were more likely to inherit HLA DR4 than the non‐affected offspring. It is concluded first that linkage studies of RA using the affected sib‐pair method are not invalidated, which would have been the case in the presence of preferential transmission of HLA to all offspring. Secondly, HLA and specifically HLA‐DR4 does co‐segregate with RA, and, finally, parental RA status, independent of DR4, has little influence in explaining the genetic susceptibility to RA.
Haplotypes bearing HLA‐A, ‐B, and ‐DR: Bf and C4 genes in rheumatoid arthritis families
Authors: Sanders P. A. , Thomson W. , Dyer P. A. , Grennan D. M.
Published: October 2008

We have compared haplotypes bearing HLA‐A, ‐B, ‐DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There were no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4‐bearing haplotypes, the haplotype B15‐BfS‐DR4 was increased fourfold and the B44‐BfS‐DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44‐C4B*Q0‐C4A3‐BfS‐DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty‐two RA patients were HLA‐DR4 negative. No single DR4 negative haplotype was found to confer significantly increased susceptibility to RA.
Definition of the HL A‐Aw43 antigen
Authors: Martell R. W. , Torr E. D. Du , Joysey V. , Doran T. J. , Cross D. , May R.
Published: October 2008

The HLA antigen Aw43 has been observed only in Southern African populations. In order to confirm its identity and clarify its definition, ten cells with this specificity were shipped to laboratories in England, the United States of America and Australia to be tested with the sera from the 10th International Histocompatibility Workshop. The results of tests on nine of these cells which were sufficiently viable indicated that HLA‐Aw43 is a distinct serological specificity which could be distinguished from both the A10 cross‐reacting group (A25, A26 and Aw34) and A29. The Aw43 specificity segregated in two South African Negro families, and occurred commonly in association with Bw70. The occurrence of HLA‐Aw43 in South African Caucasoids, in contrast to its absence in other Caucasoid groups, is probably due to genetic admixture with indigenous South African populations.
HLA and Chinese IgA nephropathy in Taiwan
Authors: Huang C.‐C. , Hu S.‐A. , Lin J.‐L. , Wu J.‐H.
Published: October 2008

No HLA‐A, B, C, DR, DQ association was found in 80 Chinese IgA nephropathy patients. In addition, no prognostic genetic marker was discovered. The subgroup of those with gross hematuria was immunogenetically distinct from the subgroup of those without gross hematuria.
HLA‐Dw ‘RSH’: a new HLA‐Dw specificity associated with HLA‐DRw18(3)
Authors: Oudshoorn M. , Toit E. D. du , Taljaard D. G.
Published: October 2008

The present study describes a new HLA‐Dw specificity, Dw‘RSH’. HLA‐Dw‘RSH’ is associated with DRw18(3) and is clearly different to the DRw17(3) associated specificity Dw3. Dw‘RSH’ was shown to be the most common Dw specificity found in the South African (SA) Negroes (gf=0.10) and was less common in Cape Coloureds (gf=0.01). The specificity was absent in the SA Caucasoids tested. Dw‘RSH’ is part of the common Negro haplotype Bw42, DRw18, DQw4 which is seen as commonly in the SA Negroes as the B8, DRw17, DQw2, Dw3 haplotype is seen in the Caucasoids.
Biochemical HLA typing: a population study in 112 Caucasians
Authors: Hajek‐Rosenmayr A. , Jungl L. , Oppolzer E. , Stammler M. , Gruber G. , Kirnbauer M.
Published: October 2008

In order to define frequencies and associations of biochemically defined HLA‐A and ‐B specificities and their variants and subtypes in a Caucasian population, biochemical HLA typing was performed in a panel of 112 Austrians. Already known rare variants of HLA‐A2, A3, A30, Aw33 and B39 and the more frequent subtypes of HLA‐B27, B35, B44 and, in addition, a so far unknown variant of HLA‐B18 were present in the panel. Family segregation analyses of the biochemically defined HLA class I variants revealed that they could be found only in certain rare haplotypes, most of them in high linkage disequilibrium. The basic variant of HLA‐A30, for example, obviously occurred only in the HLA‐A30, B49, Cw7 haplotype, similar to the Aw33 acidic variant, which was exclusively found in the Aw33, Bw58, Cw3 haplotype. None of the biochemical variants was found in frequent common haplotypes.
HLA‐B SNA antigen: a BW6 associated B locus antigen belonging to the B5 CREG
Authors: Andrien M. , Reekers P. , Stordeur P. , Vandercruys M. , Dupont E.
Published: October 2008

A new B locus antigen has been found in members of two unrelated families and in a patient originating from Morocco belonging to the Berber population. A complete analysis has been performed with antisera from the 9th and 10th IHWS defining the B5 CREG antigens. Serology, absorption experiments and family studies indicate that SNA antigen is a Bw6 associated subtype of B5 antigen closely related to but clearly distinct from each of the B5 CREG antigens. One‐dimensional isoelectric focusing study (1D‐IEF) confirms that the SNA antigen precipitates as a B locus gene product and has an isoelectric point identical to that of B w52 and one of the charge variants of B51.
Are HLA class II genes controlling susceptibility and resistance to Brazilian pemphigus foliaceus (fogo selvagem)?
Authors: Petzl‐Erler M. L. , Santamaria J.
Published: October 2008

In order to investigate the possible association between Brazilian pemphigus foliaceus and HLA, we studied 48 patients and 74 matched controls, all Brazilian Caucasoids, for HLA‐A,B,C; DR1 to DRw8 and DQw1 to DQw3. The frequencies of DR1, DR4 and B16 were significantly increased, while DR7 was significantly decreased among the patients. Furthermore DQw2, likewise the DR specificities associated with it ‐ DR3 and DR7 ‐ never occurred among the patients in the absence of the susceptibility markers DR1, DQw1 or DR4, DQw3. Acting on these findings, we suggest that at least two MHC‐class II genes are involved in the pathogenesis of Brazilian pemphigus foliaceus: at least one gene, associated to DR1,DQw1 and to DR4,DQw3, confers susceptibility and at least one gene, associated to DR7,DQw2 and DR3,DQw2, confers resistance. The susceptibility gene(s) seem(s) to be epistatic to or dominant over (if allelic) the resistance gene(s). Both are dominant over other alleles at their locus (or loci).
HLA‐antigens in renal transplanted patients with varicella‐zoster infection
Authors: Forsberg B. , Johnson U.
Published: October 2008

The frequency of the HLA B 40 antigen was significantly higher among renal transplanted patients with herpes zoster infection than in controls. The presence of HLA B 40 may be related to impaired immune response in transplanted and immunosuppressed carriers.
DNA‐DR typing shows HLA‐DRw11 RFLPs are increased in frequency in both progressive systemic sclerosis and CREST variants of scleroderma
Authors: Dunckley H. , Jazwinska E. C. , Gatenby P. A. , Serjeantson S. W.
Published: October 2008

DNA‐DR typing of patients with both Progressive Systemic Sclerosis and CREST variants of Scleroderma has shown an increase in frequency of DRw11 RFLPs. The frequency of DQw7 was also increased in the patient groups, but this was due to linkage disequilibrium with DRw11.
A polymorphic monoclonal antibody, PLM10, that reacts with B‐cell lines earring HLA‐DPw1, DPw5, and DP “Cp63”
Authors: Maeda H. , Hirata R. , Hitomi Y. , Tohyama H.
Published: October 2008

A monoclonal antibody, PLM10, that reacted with B‐cell lines of DPw1, DPw5, and DP “Cp63” phenotypes was produced. The antibody was IgM isotype and efficiently lysed B cells but not T cells from approximately 50% of normal Japanese, raising the possibility of serologic typing of the DP polymorphism by the conventional complement‐dependent cytotoxicity test.
Strong association of HLA‐DR3 in Chinese patients with idiopathic membranous nephropathy
Authors: Huang C‐C.
Published: October 2008

The frequency of HLA‐DR3 was significantly increased in 22 adult Chinese patients with idiopathic membranous nephropathy. The frequency of HLA‐Aw33 was also increased through close linkage disequilibrium with DR3.
HLA typing in 67 Italian patients with idiopathic hemochromatosis and their relatives
Authors: Panajotopoulos N. , Piperno A. , Conte D. , Mandelli C. , Cesana M. , Mercuriali F. , Fiorelli G. , Bianchi P. A. , Fargion S.
Published: October 2008

The frequency of HLA A3 and B7 antigens was significantly higher in 67 unrelated patients with idiopathic hemochromatosis (IH) than in 700 controls (62.7% vs 22.5%, p < 10−8 and 26.9% vs 9.3%, p < 10−3, respectively). A3 B7, A3 B35 and A3 B5 were significantly more frequent in 72 haplotypes linked to IH gene than in 278 control haplotypes. The prevalence of B35 and A3 B35 was significantly higher in IH patients from North‐Eastern Italy than from other regions (60% vs 21%, p < .05 and 54.5% vs 8.2%, p < 0.0001, respectively). All 15 siblings HLA identical to the respective proband were homozygous for IH with variable expression of the disease, whereas minor abnormalities of iron‐related indexes were present in 23% of heterozygous relatives. Homozygous‐heterozygous mating probably occurred in three of 40 families, accounting for the overt disease in three offspring and in one HLA semi‐identical sibling; however, in this last case the possibility of a recombination event cannot be excluded.
MicroELISA assays of anti‐HLA activity and isotype of human monoclonal antibodies
Authors: Hancock R. J. T. , Yendle J. E. , Bradley B. A.
Published: October 2008

Both monoclonal human antibodies to HLA‐DR antigens and supernatants from oligoclonal B‐cell lines can be conveniently screened for activity by microELISA assays which use 1/10 of the volume of reagents used in conventional ELISA assays. Target cells are fixed to the bases of wells in Terasaki plates, 5 μl volumes of supernatants incubated in these wells, and target bound antibody detected by peroxidase‐conjugated anti‐immunoglobulin followed by the substrate ABTS(2,2′‐azino‐di‐(3‐ethylbenzthiazoline sulphonate). The plates are read on a micro EIA reader. Supernatants can also be assayed for immunoglobulin content and isotype in Terasaki plates by coating the wells with isotype‐specific anti‐immunoglobulin, adding test supernatant and developing with appropriate peroxidase‐conjugated anti‐immunoglobulin sera and ABTS. When assaying for immunoglobulin content, the plates can be read either with a reader or by eye. Advantages and modifications of these procedures are discussed. There are no apparent practically important disadvantages to these procedures as compared with more conventional ELISA assays.
HLA‐D region heterogeneity in a Nigerian population
Authors: Okoye R.C. , Ollier W. , Jaraquemada D. , Awad J. , Navarrete C. , Cutbush S. , Carthy D. , Dos‐Santos A. , Fstenstein H.
Published: October 2008

HLA class II antigens were studied in a panel of 130 Nigerians. Complex patterns of associations were seen between HLA‐Dw, ‐DR and ‐DQ specificities, differing widely from those reported for other populations. A number of Dw types were associated with the same DR antigen: Dw′1N′ and Dw′BERN′ with DR1, Dw2 and Dw′2N′ with DR2, Dw5 and Dw′SN′ (Dw5+Dw′F5′) with DRw11. It was also observed that a Dw type associated with more than one DR antigen: HLA‐Dw3 was assigned to individuals who were DR3 negative and similarly Dw10, Dw13 and Dw14 to individuals negative for DR4. HLA‐DRw8 and Dw8 were completely dissociated in Nigerians, and Dw8 did not show a preferential DR association. These results demonstrate that DR and DQ identity between HTC stimulator and responder cell is not necessarily a prerequisite for Dw to be assigned. Preliminary studies show that subtypes of HLA‐Dw1 and Dw8 detected by HTC typing correlate with restriction fragment length polymorphisms (RFLPs) detected with a combination of Bgl II enzyme and DRA/DRB cDNA probes. HLA‐DP antigen frequencies differed between Nigerians and British Caucasoids. The most common DP antigen in Nigerians was DPw1, compared with DPw4 in Caucasoids. HLA‐DPw6 appeared to be absent or rare in both Nigerians and British Caucasoids. Only five out of 68 Nigerians tested were assigned two DP specificities. The association between HLA‐DR3 and DPw1 reported in Caucasoid panels was absent in Nigerians.
Lymphocyte proliferative response to mitogenic monoclonal antibodies in systemic sclerosis. Evidence for unresponsiveness to murine monoclonal antibodies of IgG1 isotype
Authors: Valentini G. , Giarrusso P. Carandente , Gualdieri L. , Corbo L. , Alfinito F. , Turco M. C. , Venuta S. , Giordano M.
Published: October 2008

Proliferative response of peripheral blood mononuclear cells to phitohemoagglutinin and anti‐CD3 mitogenic monoclonal antibodies (MoAbs) of the IgG2a (OKT3) and IgG1 (PanT2, CLB T3/4.1) isotypes was studied in 39 patients with systemic sclerosis (SSc) and in 82 control subjects. The effect of IL2 on this response was also investigated. No difference in the response to PHA and to IgG2a anti‐CD3 MoAb OKT3 was seen between scleroderma patients and controls. Both the patient and control groups contained responders and non‐responders to IgG1 anti‐CD3 MoAbs. The percentage of non‐responders was significantly higher in scleroderma patients than in controls. When purified lymphocytes from non‐responder scleroderma patients were cultured with monocytes from control responders, proliferative response to IgG1 MoAbs was restored. Our results show that monocytes from patients with systemic sclerosis bear a defect leading to IgG1 unresponsiveness by T lymphocytes.
Definition of DRw10 by restriction fragment length polymorphism
Authors: Lee S. , Nuñez‐Roldan A. , Dwyer E. , Pompeo L. , Winchester R.
Published: October 2008

To better define the presence of the DRw10 haplotype which has sometimes proved difficult to type by using serologic reagents, Southern blot analysis was performed on seven DRw10 heterozygous individuals with rheumatoid arthritis. Using the restriction enzymes Taq I or BamH I, the restriction fragment length polymorphism (RFLP) pattern for the DRw10 haplotype was clearly distinguishable from that of other DR alleles. Digestion with Taq I revealed a unique DRβ/Taq I 12.20 fragment. A characteristic DRβ/Taq I 4.60 fragment was also present only in DRw10 and DRl haplotypes. Digestion with the restriction enzyme BamH I revealed a DRβ/BamH 1 5.07 fragment also present in DRw10 and DR1 haplotypes, and a DRβ/BamH I 4.30 fragment shared with the DRw52 and DR2 haplotypes but not found in DR1 haplotypes. The pattern was readily distinguished from those given by the haplotypes DR4, 7 and w9. Family studies of five individuals demonstrated appropriate segregation of the restriction fragments. In particular, segregation of DRw10 haplotypes from DRl haplotypes was clearly shown in a family in which the DRw10 haplotype was associated with rheumatoid arthritis in two individuals. Southern blot analysis proved to be a useful alternative method for identifying the DRw10 allele in certain combinations where this allele has ben difficult to define serologically.
A method of HLA class II typing using non‐radioactive labelled oligonucleotides
Authors: Eliaou J‐F. , Humbert M. , Balaguer P. , Gebuhrer L. , Amsellem S. , Bétuel H. , Nicolas J‐C. , Clot J.
Published: October 2008

The typing of HLA class II genes using molecular biology techniques has brought undoubtedly new insights in the analysis of their polymorphism. Particularly interesting is the dot‐blot analysis of enzymatically‐amplified genomic DNA hybridized with sequence‐specific oligonucleotides. In order to use this technique of typing on a routine basis, we established a non‐radioactive detection method of enzymatically‐amplified genomic DNA dot‐blots. We could clearly demonstrate that, using biotin‐labelled specific oligonucleotides, it was possible to specifically discriminate between DQBl first domain DNA sequences displaying three, two or even only one base‐pair difference at a given codon position. The very satisfactory sensitivity level reached by this non‐radioactive detection method could safely allow its use for clinical applications of HLA typing at the DNA level.
HLA antigen and haplotype frequencies in Greeks
Authors: Pachoula‐Papasteriadis C. , Ollier W. , Cutbush S. , Economidou J. , Festenstein H.
Published: October 2008

A random panel of 189 healthy Greek subjects was HLA typed for A, B and DR antigens. The alleles of these loci were found to be in Hardy‐Weinberg equilibrium. Compared with other European Caucasoid populations, the frequencies of A9, B5, B18, B35, DR2 and DR5 were raised and that of B8 lowered. Significant linkage disequilibrium was found between a number of A/B, B/DR and A/DR antigen combinations. Some of the antigen associations usually seen in Caucasoid populations were also present in this sample (A1‐B8‐DR3, B14‐DR1, B15‐DR4) although others were missing (A3‐B7‐DR2, B35‐DR1, B44‐DR4). In addition, some antigen combinations have not been previously described. The most frequent two locus haplotypes in the Greek population are B8‐DR3 and B18‐DR5.
HLA linked immune response to S and pre‐S2 gene products in hepatitis B vaccination
Authors: Marescot M. R. , Budkowska A. , Pillot J. , Debre P.
Published: October 2008

In order to detect a possible HLA linked genetic control of human immune responses to hepatitis B virus, forty healthy adult persons of the same age typed for HLA‐A, ‐B and ‐DR antigens, were vaccinated against virus hepatitis B and sequentially tested for anti‐HBs and anti‐pre‐S2 antibodies. They received three injections of Hevac‐B Pasteur vaccine, the second 1 month and the third 3 months after the first. Following the third immunization, 38 individuals (95%) had a protective level of anti‐HBs antibodies and 17 (42.3%) had a positive level of anti‐pre‐S2 antibodies. HLA‐A11 antigen was significantly more frequent (pc = 0.007) among anti‐HBs high responders than low responders. In addition, anti‐HBs high responders were more frequently HLA‐DR1, and less frequently HLA‐DR4 and DR7 positive; corrected values, however, were not significant. Anti‐pre‐S2 high responders showed an apparent increase of HLA‐B7, B14 or DR3 antigens, when compared to low responders (pc not significant).
An estimate on the frequency of duplicated haplotypes and silent alleles of human C4 protein polymorphism. I. Investigations in healthy Caucasoid families
Authors: Steuer M. , Mauff G. , Adam C. , Baur M.P. , Bender K. , Goetz J. , Goldmann S. F. , Hauptmann G. , Neugebauer M. , Tongio M. M. , Uring‐Lambert B. , Wölpl A.
Published: October 2008

The frequency of duplicated and non‐expressed C4 alleles was determined by segregation analysis in 31 German and five French families with altogether 274 individuals by submitting the complete data from C4 protein phenotyping, including C4 beta chains, and the other classical MHC markers to the family analysis programme (FAP). From 120 unrelated German haplotypes the following frequencies were derived for silent alleles: C4A*Q0 0.2000, C4B*Q0 0.2083, and for the total of homo‐ and heteroduplicated C4A resp. C4B alleles: C4“DA”* 0.1333, C4“DB”*0.1000. The true occurrence of the duplicated C4A*2, “DB*21” haplotype, first observed in French families, was found to be 0.0250 in the German sample. While the frequency of duplicated C4 haplotypes confirms earlier estimates, the increase in the frequency of silent alleles corresponds to those assumed from investigations at the DNA level. The results demonstrate classical protein typing with inclusion of C4 beta chain types to be an indispensable and powerful tool for haplotype recognition; they support the hypothesis that deletion at one C4 locus is accompanied by duplication at the other in a majority of haplotypes.
Two cytotoxic human‐human hybridoma antibodies to HLA: TrAH10 (anti A3.1) and TrAG2 (anti B7,Bw42)
Authors: Hansen T. , Bratlie A. , Johansen B. , Hannestad K.
Published: October 2008

Two cytotoxic human‐human hybridoma IgM antibodies to HLA were generated by EBV transformation of PBMC from multiparous women and fusion of EB V transformed cells with the human fusion partners KR4 or KR12. Both mAbs required the sensitive immunomagnetic cytotoxicity method to display killing of freshly prepared PBMC. One mAb (TrAHIO) was specific for HLA‐A3. Strikingly, TrAHIO reacted much more strongly with lymphoblastoid cell lines of HLA‐A3.1 than of the rare variant HLA‐A3.2, previously detected by cytotoxic T cells. Thus, in the microcytotoxicity test, the titer of conecentrated TrAHIO was approximately 2000 times higher for A3.1 as compared to A3.2, and a clear difference was also observed in radioimmunoassay. Since the two HLA‐A3 variants differ by only two amino acids at positions 152 and 156 of the α2‐domain's α‐helix, the epitopes defined by the mAb TrAHIO and HLA‐A3.1 specific cytotoxic T cells must be closely related. The observations with TrAH10 suggest that the HLA polymorphism detected by human mAbs may turn out to be as extensive as the T‐cell defined HLA polymorphism. The other mAb (TrAG2) bound B7 and Bw42 with equal strength, and in addition bound weakly to some cells that were Bw22 or B39. Magnetic polymerbeads coated with affinity purified human mAbs TrAHIO or TrAG2 formed rosettes with EBV transformed cells carrying relevant HLA antigens; however, rosette formation with freshly isolated PBMC was very weak and unsuitable as a typing assay.
Specificity of HLA restricting elements for human nickel reactive T cell clones
Authors: Emtestam L. , Carlsson B. , Marcusson J. A. , Wallin J. , Möller E.
Published: October 2008

In order to study the fine specificity of HLA class II restriction, we have established nickel specific T cell clones from a nickel allergic patient. Cells were cloned by limiting dilution after primary stimulation and selection of nickel specific blasts. Several clones were established which were all shown to carry the CD4 marker. All clones were shown to be completely blocked by monoclonal antibodies directed against DR. antigens, but unaffected by antibodies against DQ or DP, thus demonstrating their DR specificity. For the study of HLA class II restriction, a panel of cell donors was carefully HLA typed by including the use of DRB and DQB cDNA probes. Specificity analysis, using allogeneic antigen presenting cells, revealed that the clones were either restricted to DR3‐ or DR4‐like molecules, which is consistent with the fact that the donor was DR3, DR4 positive. However, the studies also revealed that the fine specificity of the DR3 and DR4 restriction could not be completely assessed by serological and genomic typing of panel cells. This indicates that cellulary defined HLA restriction elements recognized by T cells cannot be defined properly with available class II typing methods, and the results of these experiments documented the additional polymorphism of class II restriction elements. The clonal specificity analysis has shed further light on the biologically relevant level of DR polymorphism.
Multiple sclerosis patients have a high frequency of an HLA‐DQβ epitope defined by a human‐human hybridoma antibody
Authors: Kolstad A. , Hannestad K. , Vandvik B. , Vartdal F.
Published: October 2008

Epstein‐Barr virus (EBV) transformed B‐cells from patients with multiple sclerosis (MS) and healthy controls were analysed for reactivity with the HLA‐DQ‐specific human‐human hybridoma Ab TrB12 (anti‐DQw6 + DQw8 + DQw9) by indirect immunofluorescence (IIF). Positive results were obtained with 34 out of 35 MS patients (97.1%) and 79 out of 106 controls (74.5%) (p <0.005, RR = 11.6). Thus, DQ molecules that express the TrB12 epitope may contribute to the susceptibility to develop MS.
Oligonucleotide‐genotyping as a method of detecting the HLA‐DR2 (DRw15)‐Dw2, ‐DR2 (DRw15)‐Dw12, ‐DR4‐Dw15, and ‐DR4‐D“KT2” haplotypes in the Japanese population
Authors: Obata F. , Ito I. , Kaneko T. , Ohkubo M. , Ishimoto A. L. , Abe A. , Kashiwagi N.
Published: October 2008

We synthesized pairs of four different oligonucleotides, F22, F29, F42, and F158, to analyse the HLA‐DR2 (DRw15) and ‐DR4 haplotypes in the Japanese population. After enzymatically amplifying the HLA‐DRB1 gene, we hybridized the oligonucleotide probes with DNA extracted from 42 donors. Hybridization was completed between F22 and the DNA of haplotype DR2 (DRw15)‐Dw2, between F29 and the DNA of DR2 (DRw15)‐Dw12, between F42 and the DNA of DR4‐D“KT2”, and between F158 and the DNA of DR4‐Dw15. In keeping with the nucleotide sequences of the probes, F29 hybridized also with DNA from the DR9‐Dw23 haplotype and F158 with that from some of the DRw8 haplotypes (DRw8‐Dw8.3) in the Japanese population. Results of this study demonstrate that the four oligonucleotides make useful probes for detecting the haplotypes above.
Nco I Restriction Fragment Length Polymorphism (RFLP) of the Tumor Necrosis Factor (TNFα) region in four autoimmune diseases
Authors: Fugger L. , Morling N. , Ryder L. P. , Georgsen J. , Jakobsen B. K. , Svejgaard A. , Andersen V. , Oxholm P. , Karup Pedersen F. , Friis J. , Halberg P.
Published: October 2008

The two‐allele NcoI Restriction Fragment Length Polymorphism (RFLP) of the TNFα region yielding bands of 5.5 and 10.5 kb was investigated in patients with systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P‐JRA). rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In all four diseases, we found a decreased frequency of the 10.5 kb allele which, however, was significant only in the SLE group. In all conditions except RA, the frequency of the 5.5. kb fragment was increased. In pSS and SLE, the frequency of HLA‐B8 was increased in 5.5. kb fragment positive patients compared with corresponding controls and thus, the increase of this band and the decrease of the 10.5 kb band may be secondary to HLA‐B8 associations owing to strong positive linkage disequilibrium between HLA‐B8 and the 5.5. kb band.
Hyperimmunized patients do not need to wait for an HLA identical donor
Authors: Claas F. H. J. , Leeuwen A. van , Rood J. J. van
Published: October 2008

Hyperimmunized patients tend to accumulate on rend transplant waiting lists because their high level of sensitization leads to positive crossmatches with almost all potential organ donors. The origins of sensitization and the different efforts made to find cross‐match negative donors for these patients are discussed. Special emphasis is given to a local strategy based on the determination of HLA‐A and ‐B mismatches, against which the patient did not form allo‐antibodies, the so‐called acceptable mismatches. Kidney donor selection is bud on compatibility with the patient's own HLA‐antigens in combination with the acceptable HLA‐A and ‐B antigens, and can be operated from a central organ‐sharing office. The acceptable HLA mismatches are often identical with or include the non‐inherited HLA class I antigens of the mother (non‐inherited maternal antigens: NLMA).
Scandiatransplant 20 years
Authors: Flatmark A.
Published: October 2008

The first kidney transplant in Scandinavia was performed in 1956 by the late Professor Leif Efskind in Oslo, Norway. During the following 7‐year period he did another four necro‐kidney transplants. The tint living related kidney transplant was performed at Ullevå Hospital in Oslo in 1963. In 1964 kidney transplantation programs were started in Helsinki, Stockholm and Aarhus, followed by Gothenburg in 1965. By the end of 1970 programs had also started in Copenhagen, Uppsala, Lund/Malmö and Odense. At present, there are 10 kidney transplant centers in Scandinavia: four in Denmark, four in Sweden, and one each in Finland and Norway. By the end of 1968 a total of 358 kidney transplants had been performed in Scandinavia. Of these, 169 (47%) were from living related donors. This new treatment modality called for closer cooperation between the Nordic countries, and during the last 20 years cooperation has ken broadened through two working bodies: an expert committee and the Scandiatransplant organization.
Studies of expression of the DQß promoter and its 5′ deletion derivatives in normal and mutant human B cell lines
Authors: Sakurai M. , Strominger J. L.
Published: October 2008

A series of 5′ deletion test plasmids barboring promoter sequences of the HLA‐DQβ gene fused to the bacterial chloramphenicol acetyl transferase (CAT) gene were constructed. Transient CAT expression from these constructs in several types of cells was employed to examine the role of the promoter sequence in the regulation of DQß gene expression. The DQß constructs drove CAT expression in Raji cells (human Burkitt lymphoma cells) to at least 25‐fold or 50‐fold higher levels than in Hela cells (human cervical carcinoma cells) or Jurkat cells (human T‐leukemia cells), respectively. A short promoter sequence of −160 bp containing the conserved × and Y sequences was sufficient for expression in Raji cells, and deletion to −106 bp which interrupted the × sequence abolished the expression. Sequences further upstream to −160 bp as far as −2500 bp which included an Ig‐like octamer appeared to have no effect on expression in Raji cells. Thus, the promoter up to −160 bp has all of the sequences required for B cell specific expression of CAT in this assay. CAT expression from the 5′ deletion constructs introduced into RJ2.2.5 and 6.1.6 cells (class II‐negative mutant B cells Lines) was also examined. None of the 5′ deletion constructs, including that with −160 bp of promoter, showed CAT expression in these cells, suggesting that a transcriptional factor(s) required for the activity of the DQß promoter was missing m these cells. Moreover, the −160 to −66 bp sequence (including the × and Y elements), which functions as a B cell specific enhancer, was inactive in the mutant cells. Thus, the missing factor(s) are required for the enhancer function of this fragment.
The absence of 21‐OH A and C4 B genes is a constant characteristic of the “Sardinian” HLA extended haplotype A30 Cw5 B18 BfF1 DR3 DRw52 DQw2
Authors: Carcassi C. , Porcella R. , Manca M.L. , Orrrù S. , Nasa G. La , Contu L.
Published: October 2008

The genomic DNA of 25 unrelated individuals with HLA haplotype A30 Cw5 B18 B/F1 DR3 DRw52 DQw2 was digested with the restiction enzyme Taq I and hybridized with cDNA probes for C4 and 21·OH genes. Eighteen individuals and a non‐Sardinian reference cell (DUCAf) were homozygous for the entire extended haplotype, six individuals were heterozygous for the HLA‐A locus and homozygous for the rest of the same haplotype. All of the 18 homozygous individuals, four of the six heterozygous subjects and the DUCAF cell revealed the absence of two fragments at 3.2 and 2.4 kb corresponding to the 21·OH A gene, and the absence of fragments corresponding to the C4 B “long” or “short” gene. The contemporary absence of the 21·OH A and C4 B genes seems to be a constant characteristic of this extended haplotype in the Sardinian population and suggests that this and other extended haplotypes bearing C4 A or C4 B null alleles could be ancestral haplotypes which never duplicated at these loci.