bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of antenatal and delivery care before and after the implementation of a prevention of mother‐to‐child HIV transmission programme in Côte d’Ivoire
Authors: Delvaux Thérèse , Diby Konan Jean‐Paul , Aké‐Tano Odile , Gohou‐Kouassi Valérie , Bosso Patrice Emery , Buvé Anne , Ronsmans Carine
Published: October 2008

Objective  To assess whether implementation of a prevention of mother‐to‐child HIV transmission (PMTCT) programme in Côte d’Ivoire improved the quality of antenatal and delivery care services.

Methods  Quality of antenatal and delivery care services was assessed in five urban health facilities before (2002–2003) and after (2005) the implementation of a PMTCT programme through review of facility data; observation of antenatal consultations (n = 606 before; n = 591 after) and deliveries (n = 229 before; n = 231 after) and exit interviews of women; and interviews of health facility staff.

Results  HIV testing was never proposed at baseline and was proposed to 63% of women at the first ANC visit after PMTCT implementation. The overall testing rate was 42% and 83% of tested HIV‐infected pregnant women received nevirapine. In addition, inter‐personal communication and confidentiality significantly improved in all health facilities. In the maternity ward, quality of obstetrical care at admission, delivery and post‐partum care globally improved in all facilities after the implementation of the programme although some indicators remained poor, such as filling in the partograph directly during labour. Episiotomy rates among primiparous women dropped from 64% to 25% (P < 0.001) after PMTCT implementation. Global scores for quality of antenatal and delivery care significantly improved in all facilities after the implementation of the programme.

Conclusions  Introducing comprehensive PMTCT services can improve the quality of antenatal and delivery care in general.
Can VISION 2020 be implemented in rural government settings? Findings from two programmes in Tanzania
Authors: Eliah Edson , Shayo Andrew , Gendo Charles , Courtright Paul , Theraney Manisha , Lewallen Susan
Published: October 2008

Objective  To generate information on essential components and the cost recovery potential of VISION 2020 programmes in rural Africa.

Methods  We took a structured approach to planning, training, implementation and supervision of programmes in Singida and Mara regions, Tanzania involving both government and non‐government partners. Extensive mentoring was provided to monitor activities and costs.

Results  Annual numbers of patients receiving eye care increased sevenfold, cataract surgeries by a factor of 2.6 and spectacles dispensed by a factor of 16. Running costs were shared; the government provided 40–60%, non‐government organisations (NGOs) 25–45%, and patient fees 15%.

Conclusion  Comprehensive eye care can be delivered with cooperation among partners. However, continued coordination and cooperation from government and NGOs are critical to reach VISION 2020 goals.
Occurrence, productivity and spatial distribution of key‐premises in two dengue‐endemic areas of Rio de Janeiro and their role in adult Aedes aegypti spatial infestation pattern
Authors: Maciel‐de‐Freitas Rafael , Peres Roberto C. , Souza‐Santos Reinaldo , Lourenço‐de‐Oliveira Ricardo
Published: October 2008

Objectives  To evaluate: (1) the occurrence, maintenance, productivity, spatial distribution and premise condition index score of Adese aegypti‐infested houses and key‐premises in a suburban district (Tubiacanga) and a slum (Favela do Amorim) of Rio de Janeiro and (2) the role of these factors in adult Ae. aegypti female spatial distribution.

Methods and Results  A total of 2456 premises were inspected for immature and 1100 for adult collection. Key‐premises corresponded to 16.08% and 17.86% of infested houses in Tubiacanga, and 13.5% and 11.1% in Favela do Amorim, during the dry and wet seasons, respectively. Key‐premises held significantly more immature Ae. aegypti, pupae and larvae than infested houses in Favela do Amorim and Tubiacanga during the dry and wet seasons. In Favela do Amorim, key‐premises had a significantly higher PCI score than infested but non‐key houses.

Conclusion  The spatial distribution of key‐premises and adult Ae. aegypti females was often congruent, indicating that key‐premises influence the infestation pattern observed in the study areas.
Expression of Ia antigens on freshly dissociated mouse thyroid follicles demonstrated by immunofluorescence
Authors: Boudier I.‐A. , Courageot J. , Alquier C.
Published: October 2008

Iak antigens were detected by indirect immunofluorescence on CBA mouse thyroid follicles. Isolated thyroid follicles, free of lymphocyte contamination, were obtained by collagenase treatment and mechanical disruption; they were then cytocentrifuged on glass slides. This material was incubated with polyclonal or monoclonal anti Iak antibodies followed by FITC‐conjugated F(ab')2. Subsequent microscopic observations of these open thyroid follicles revealed that Iak antigens were spontaneously expressed. Labelling was distributed preferentially on the thyrocyte cell surface and, to a lesser extent, on intracellular organelles. Conversely, nuclei were never stained. In some cases, labelling was mottled. Ia antigens may have been previously unobserved because, beside autoimmune disorders, they are present in such small amounts that detection is very difficult. The fact that Ia expression is independent of morphological signs of spontaneous autoimmune thyroiditis (particularly, lymphocyte infiltration of follicles), raises the problem of correlation between the autoimmune disorders and Ia expression.
HLA‐DR and ‐DQ DNA genotyping in seven populations of Asia‐Oceania and Australia
Authors: Kohonen‐Corish M. R. J. , Dunckley H. , Serjeantson S. W.
Published: October 2008

Haplotype patterns of HLA‐DR and ‐DQ restriction fragment length polymorphism (RFLPs) were compared in seven populations in the region of Asia‐Oceania: Australian Caucasoids, Melanesians, Micronesians, Polynesians, Chinese, Koreans and Japanese. Several DRP RFLP patterns, including those correlating with DR2, 4, 5, w6, 7 and w8 in Caucasoids, were associated with multiple DQα/DQβ RFLP haplotypes, of which only two occurred universally ‐ one associated with DR4 and one with DR5. RFLPs revealed new population or group specific characteristics, which had not been previously discovered using serological or cellular HLA typing techniques. The populations of Asia‐Oceania have some features of the class II RFLPs in common, which are distinctly different from Caucasoids. On the other hand, a number of characteristics distinguish between the various Asian and Pacific groups. This study demonstrates the power of RFLP analysis of closely linked genes in population genetics, and shows the value of ethnic comparisons in further characterizing the polymorphisms of the HLA class II genes.
Immune response to H‐2 class I antigens on platelets. I. Immunogenicity of platelet class I antigens
Authors: Frangoulis B. , Besluau D. , Chopin M. , Degos L. , Pla M.
Published: October 2008

Purified allogeneic murine platelet suspensions were found unable to induce primary anti‐H‐2 class I antibody or T cell proliferative responses. In contrast, the same platelet suspensions could elicit secondary anticlass I responses. The secondary responses were not due to contaminating leucocytes. Possible explanations, the lack of acolyte determinants (class II or non‐H‐2) on platelets or inappropriate layout and/or structure of their class I antigens, are discussed. These findings emphasize the importance of sufficient leucocyte depletion before platelet transfusion in the human.
Hydatidiform mole and HLA. III. HLA‐antigen expression related to genomic origin
Authors: Hansen H. E. , Vejerslev L. O. , Larsen S. Olesen
Published: October 2008

In 52 conceptuses with known genomic origin, HLA determination was performed on whole villi and/or stromal cell cultures. In 26 androgenetic, diploid conceptuses, one or two paternal HLA‐A, B haplotypes were found; twenty‐four triploid conceptuses with two paternal and one maternal chromosome sets showed either one maternal and one paternal haplotype or one/two paternal HLA‐A, B haplotypes. Consequently, androgenesis could not be demonstrated by lack of maternal antigens alone. Concomitant expression of three HLA haplotypes was not seen. HLA‐A2 was passed on to the conceptus, both in the genetic subgroups and in the entire series, more frequently than expected.
Erythema multiforme is associated to HLA‐Aw33 and DRw53
Authors: Lepage V. , Douay C. , Mallet C. , Binet O. , Lemarchand F. , Wallach D. , Masset M. , Colombani J. , Degos L.
Published: October 2008

Erythema multiforme is an acute eruption of the skin and mucous membranes of various aetiologies. Forty‐one unrelated patients were HLA typed for 53 specificities of the HLA‐A, B, C, DR and DQ series. Frequencies of Aw33 and DRw53 were significantly increased: Aw33. 17.0% in patients vs 2.8% in controls (corrected p = 0.01, relative risk = 7.2); DRw.53. 70.7% in patients vs 30.5% in controls (corrected p = 0.0005, relative risk = 5.5).
The polymorphism of HLA antigens in the Chinese
Authors: Lee T. D. , Zhao T. M. , Mickey R. , Sun Y. P. , Lee G. , Song C. X. , Cheng D. Z. , Zhou M. S. , Ding S. Q. , Cheng D. X. , Song F. J. , Lee P. Y. , An J. B. , Mittal K. K.
Published: October 2008

Remarkable differences were observed in antigen frequencies (AF), gene frequencies (GF) and haplotype frequencies (HF) when 2441 healthy Chinese individuals representing nine different ethnic groups and living in 14 different geographic locations were examined for the genetic distribution of the various HLA Class I and II markers. A sizable number of individuals of each ethnic group within each of the three major categories of the Chinese population, namely, Hans, Mongols, and Southern minorities, have been studied here, providing useful population statistics for applications such as determination of probabilities of paternity, comparisons for HLA and disease associations, and anthropologic studies.
Four cytotoxic human‐human hybridoma antibodies that react with HLA‐B27
Authors: Hansen T. , Bratlie A. , Hannestad K.
Published: October 2008

PBMC were isolated from a multiparous woman with HLA‐B27 specific Abs in her serum. The HLA type of the donor was A2,9;B7. The PBMC were EBV transformed, and four cell lines making cytotoxic Abs to HLA‐B27+ cells prepared. Hybridomas were constructed by fusing the EBV lines with the human fusion partner KR4. All four mAbs were of IgM isotype. One mAb (TrBH12) reacted specifically with B27+, B37+ and Bw47+ lymphoblastoid cell lines and with all B27+ PBMC except for a rare variant so far found only in one Norwegian family. Another mAb (Tr3B6) was cytotoxic for all B27+ cells tested, including the TrBH12−‐ variant; in addition, it showed weaker cross‐reactions to Bw42, B49 and a cell line with the probable phenotype B7,38. Supernatant from the Tr3B6 hybridoma was tested in lymphocytotoxicity against a panel of 658 individuals, 141 of whom were B27+. With this panel, Tr3B6 showed perfect correlation with HLA‐B27. The two last mAbs (TrCG10 and TrBFl) reacted with all B27+ cells tested, but in addition showed quite extensive cross‐reactions.
Heterogeneity in the mitogenic response of peripheral blood mononuclear cells to a pan T monoclonal antibody
Authors: Giarrusso P. Carandente , Turco M. C. , Corbo L. , Maio M. , Alfinito F. , Scala G. , Zappacosta S. , Venuta S.
Published: October 2008

Peripheral blood mononuclear cells (PBMC) from 80 normal donors were studied for their capacity to proliferate in response to Pan T2, an IgG1 monoclonal antibody (MoAb), that recognizes the CD3 complex. Forty percent of this population, regardless of sex or age, were found to be non‐responders. However, the binding of MoAb Pan T2 to T cells as studied by indirect immunofluorescence was positive in all the donors. The addition of IL 1 or IL 2 to Pan T2‐stimulated non‐responder lymphocytes did not activate T cell proliferation, while the addition of responder monocytes restored the proliferation capacity in non‐responder PBMC. The data indicate the existence of a heterogeneous responsiveness among normal individuals to a mitogenic IgG1 MoAb, and are in agreement with reports obtained using other anti‐T3 MoAbs of IgG1 isotype, i.e. UCHT1, Leu4 and WT31. This defect is reported to be a function of monocytes, related to a polymorphism of Fc receptors for mouse IgG1 on human monocytic cells.
HLA antigens in chronic lymphocytic leukemia
Authors: Linet M. S. , Bias W. B. , Dorgan J. F. , McCaffrey L. D. , Humphrey R. L.
Published: October 2008

HLA‐A, B, and C phenotypes of 88 white and 14 black patients with chronic lymphocytic leukemia (CLL) were compared with those of 3761 white and 660 black laboratory population controls, and HLA‐DR phenotypes were compared with 742 white and 236 black controls from the same population. Several statistically significant associations were found, one of which (a strongly positive association with Cw6 for whites) persisted after correction for the number of antigens tested.
High prevalence of the haplotype HLA‐A11, B27 in arthritis patients from the highlands of Papua New Guinea
Authors: Bhatia K. , Richens J. , Prasad M. L. , Koki G.
Published: October 2008

The haplotype HLA‐A11, B27 is present in significantly increased numbers in arthritis patients, over and above the numbers expected from its relative proportion in B27‐positive healthy controls, from the highlands of Papua New Guinea.
HLA‐A, B, C, DR and DQ polymorphisms in three South African population groups: South African Negroes, Cape Coloureds and South African Caucasoids
Authors: Toit E. D. Du , MacGregor K. J. , Taljaard D. G. , Oudshoorn M.
Published: October 2008

The HLA class I and II phenotypes of the three popuation groups in the Cape Province of South Africa were determined. The HLA‐A, B, and C antigens were tested in 1027 South African Negroes (Xhosa), 3716 Cape Coloureds and 1059 South African Caucasoids. This is the first study which has also included the class II antigens in the Southern African Negroes (Xhosa). The numbers tested for the DR and DQ antigens were smaller, as only typings done after the 8th Histocompatibility Workshop were included. A comparison was made between the frequencies in the Xhosa, the Cape Coloureds and the South African Caucasoids as well as the Nigerians, another group who also belong to the Bantu‐speaking division of African Negroes and who were recently studied. The antigen, gene and haplotype frequencies were estimated in all three groups, and the genetic distances calculated. Striking differences in gene and haplotype frequencies between the various populations were seen. For example, Bw42 had a phenotype frequency of 0.062 in the Cape Coloureds, 0.213 in the Xhosa and 0.004 in the South African Caucasoids. The Xhosa showed marked differences in HLA distribution compared to the other Negro group (Nigerians), which can be attributed to a Khoisan admixture, e.g. HLA‐DR4 had a phenotype frequency of 0.134 in the Xhosa and only 0.010 in the Nigerians. The haplotype B8, DR3, seen in association with many autoimmune diseases, had a significant delta value in all three populations.
A new HTC, a PLT and a PLT clone define a split of HLA‐DR2 in the Austrian population
Authors: Hajek‐Rosenmayr A. , Holter W. , Mayr W. R. , Knapp W.
Published: October 2008

An LD defined split of HLA‐DR2, different from HLA‐Dw2, Dw12 and DB9, is observed in the Austrian population. The narrow HLA‐D specifity, defined by a new Austrian Homozygous Typing Cell (HTC), a primed lymphocyte (PLT) cell line and a PLT clone, is tentatively termed HLA‐D “WH”. Investigation of three informative families shows that HLA‐D “WH” segregated together with HLA‐DR2. In one family, even an individual heterozygous for HLA‐DR2/Dw2 and HLA‐DR2/D “WH” can be identiñed. A panel study including 90 non‐related Austrians shows that HLA‐D “WH” occuring in 6.7% of the whole panel, that is in 20% of the HLA‐DR2 positive panel members, is completely included in HLA‐DR2. HLA‐D “WH” might be comparable to other LD specificities related to HLA‐DR2, “MN2”, “FJO”, “AZH” or “GEN”.
Association of HLA‐DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects
Authors: Freidhoff L. R. , Ehrlich‐Kautzky E. , Meyers D.A. , Ansari A. A. , Bias W. B. , Marsh D. G.
Published: October 2008

Associations between HLA type and IgE or IgG antibody (Ab) responses to two well‐characterized, antigenetically non‐crossreactive components of Lolium perenne (rye grass) pollen extract, Lot p I (Rye I) and Lolp II (Rye II) were studied in two groups of skin‐test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I arid Lol II and the possession of HLA‐DR3. In view of the well‐known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti‐Lol I and anti‐Lol II mean log[Ab] levels between B8+, DR3‐vs B8‐, DR3‐subjects and B8+, DR3+ vs B8‐, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3α‐β, pair.
Laboratory animal allergy‐possible association with HLA B15 and DR4
Authors: Low B. , Sjöstedt L. , Willers S.
Published: October 2008

In 101 laboratory technicians working with laboratory animals 30 presented laboratory animal allergy (LAA) symptoms. Twenty‐seven of these LAA technicians were HLA tested. In these the HLA B15 and DR4 frequencies were raised.
HLA‐DR4 genotype frequency and gender effect in familial rheumatoid arthritis
Authors: Khan M. A. , Yamashita T. S. , Reynolds T. L. , Wolfe F. , Khan M. K.
Published: October 2008

We have studied HLA‐A, B, C, and DR antigens in 75 unrelated white families, each with multiple cases of adult‐onset definite or classical rheumatoid arthritis (RA) (by ARA criteria). There was no difference in age of onset or serological features of RA between males and females. HLA‐DR4 phenotype frequency among female (68%) and male (71%) patients also did not differ significantly. The observed frequencies of HLA‐DR4 genotypes (homozygous, heterozygous, and those lacking it) differed significantly (p<0.005) between affected and unaffected individuals. However, the observed genotype distribution did not differ from what is expected given the Hardy‐Weinburg equilibrium. There is a direct correlation between the number of DR4 allele(s) carried (two, one, or zero) and the percent affected (p<0.026 for females and p<0.052 for males). These findings highlight the importance of discerning the additional genetic determinants, including those that are gender‐associated, which influence susceptibility to RA.
HLA‐DR4 associated Dw types in rheumatoid arthritis
Authors: Ollier W. , Carthy D. , Cutbush S. , Okoye R. , Awad J. , Fielder A. , Silman A. , Festenstein H.
Published: October 2008

Frequencies of HLA‐DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n=57) compared to 31.2% in normal controls (n=96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p<0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p<0.001) in the index cases. A non‐significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p<0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA‐B antigens and DR4/Dw types to be made. HLA‐Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA‐Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data, Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and “complotype”. However, there was a suggestion of C4A3, BQO being associated with Dw4 (34.2% vs 16.1% X2= 2.9 p=ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2= 2.1 p=ns). By using a DQ‐beta probe and a range of restriction enzymes, the DNA of Dw typed DR4 positive RA patients and controls was classified into either the omega or phi restriction fragment length polymorphism (RFLP) patterns. No obvious inclination towards one of these patterns was observed with Dw4 or Dw14. However, when haplotypes were considered, the majority of the B44‐DR4‐Dw4 haplotypes were the phi pattern, whereas the Bw62‐DR4‐Dw4 and the Bw60‐DR4‐Dw14 haplotypes were omega. There was an indication that Dw10 is associated with omega and Dw13 with phi.
Lyme‐Borreliosis and possible association with HLA‐antigens*
Authors: Pflüger K.‐H. , Reimers C.‐D. , Neubert U. , Meisel C. , Trapp B. , Leittis J. , Völker B. , Münchhoff P. , Litzenberger J. , Holthausen H. , Pongratz E.
Published: October 2008

The frequencies of HLA A, B, C and DR antigens were evaluated in 220 persons from West Germany with inapparent and manifest Borrelia burgdorferi infections. Thirty‐seven forest workers showing elevated antibody titres against Borrelia burgdorferi had asymptomatic infection, and are described as stage 0. One hundred and eighty‐three patients presented with the clinical stages 1–3 of the infection. Control persons (n = 655) were typed in the same time period and by identical staff. HLA CW3 was present in 36.3% of patients as compared to 23.2% of the controls (RR = 1.88, Pcorr= 0.03) and was significantly associated with manifest infection. In addition, the antigen A2 was found slightly but not significantly more frequent in the patients (55.2% vs 44%; Pcorr= 0.41). The phenotype combination HLA A2 and Cw3, however, was significantly elevated in patients (24.6% vs 10.8%; pcorr= 0.0005). In contrast to these class 1 antigens, HLA DR3 showed a tendency of negative association with manifest infection. But this finding was not yet found to be significant (15.3% vs 25.3%; RR = 0.53, Pcorr= 0.26). The frequency of HLA DR2 showed a constant decrease from stage 0 to stage 3 (inapparent infection to late complications). Using the rank correlation coefficient of Spearman, this association was found to be significant (−1.00, p≤0.05). All other tested HLA antigens and antigen combinations showed no significant differences. The data suggest that HLA CW3 may be associated with Borrelia burgdorferi infection, whereas HLA DR2 and DR3 may be associated with less incidence of severe courses and less complications in this disorder.
Lymphocytotoxic cross‐matching performed on spleen cells: immunomagnetic technique versus current KN (Kissmeyer‐Nielsen) technique
Authors: Povlsen J. V. , Graugaard B. H. , Kissmeyer‐Nielsen F.
Published: October 2008

This paper compares the immunomagnetic (IM) and the KN lymphocytotoxic cross‐matching techniques. Only sera from patients with panel reactive antibodies and spleen cells from cadaveric donors were used. A panel study involving 60 combinations revealed 11 (18%) discrepancies. Four T‐cell cross‐matches were KN negative while IM positive. Inversely, six T‐cell cross‐matches were IM negative while KN positive (two) or doubtfully positive (four). Regarding HLA class II antibodies, one combination was found IM positive but KN negative. Out of 106 cadaveric renal allograft transplantations performed during 1987 with assistance from our laboratory, IM cross‐matching was retrospectively performed on 33 KN T‐cell cross‐match negative donor‐recipient pairs: two combinations were found T‐cell cross‐match positive. The corresponding allografts were not lost owing to hyperacute rejection involving preformed antibodies. We recommend the IM technique for HLA typing, but more experience needs to be gained before we can recommend the technique for routine cross‐matching prior to transplantation.
Expression and immunogenicity of HLA‐B27 in high‐transfection recipient P815: a new method to induce monoclonal antibodies directed against HLA‐B27
Authors: Thurau S. R. , Wildner G. , Kuon W. , Weiss E. H. , Riethmüller G.
Published: October 2008

The immunization of a (BALB/c × C57BL/6) FI mouse with murine transfectants expressing the HLA‐B27 antigen resulted in a panel of polymorphic monoclonal antibodies with specificity for HLA‐B27 and some additional HLA‐antigens. Specificity of the antibodies was defined by cytofluorometric analysis on a panel of lymphoblastoid cell lines (LCL) derived from HLA typed individuals. Three of these antibodies are cytotoxiC, and one of them inhibits B27‐specific T cell cytotoxicity. Our results indicate that HLA‐class I transfectants could be used to generate polymorphic antibodies, and that these antibodies may be helpful for HLA typing and for definition of epitopes recognized by T cells.
A cytotoxic human‐human hybridoma antibody (TrC7) specific for HLA‐A29
Authors: Kolstad A. , Bratlie A. , Hannestad K.
Published: October 2008

TrC7 is a cytotoxic IgM human‐human hybridoma anti‐HLA Ab*. Its reaction pattern with a panel of 48 HLA‐typed EBV*‐transformed cell lines and PBMC* from 348 HLA‐typed individuals con‐elated precisely with expression of HLA‐A29. TrC7 did not react with HLA‐A30, −31, −32 or −w33, which, like A29, are splits of Awl9.
Individuals with HLA‐DR blank alleles display well‐known DR‐DQ RFLPs
Authors: Wallin J. , Carlson B. , Olerup O. , Möller E.
Published: October 2008

We have characterized HLA‐DRB, ‐DQA, and ‐DQB gene polymorphism in a large number of serologically DR blank haplotypes with the restriction enzymes Taq I, Bam HI, and Pvu II, with the aim of finding new RFLPs in the Caucasian population. Locus‐specific RFLPs were combined for a definition of Taq I DR‐DQ haplotypes. All observed DNA haplotypes could be found in a control group of 100 individuals, but with a different distribution. Serologically less well‐defined DR specificities were over‐represented in the blank group, in particular the DRwl3‐associated Taq I DR‐DQ haplotype T‐13.3. We conclude that the majority of DR blank haplotypes are probably closely related or identical to previously defined DR alleles. The extent of DR polymorphism in the Caucasian population seems to be well mapped, considering the extremely small proportion of rare Taq I DR‐DQ haplotypes and lack of new patterns in this study.
Definition of a new supertypic HLA class II determinant (LAR) associated with HLA‐DR2 and ‐DR7
Authors: Colombani M. , Sansonetti N. , Lepage V. , Raffoux C. , Colombani J.
Published: October 2008

A Serum from a patient (LAR), immunized by pregnancies and blood transfusions, reacted with cells Carrying HLA‐DR2 and/or ‐DR7 specificities (titer 1:200 1:1000) Absorption‐elution experiments showed that the allo‐serum recognized a determinant shared by DR2 and DR7 cells. The high correlation coefficients (0.90–1) with these specificities suggested that the supertypic specificity LAR was carried by the first DR molecule encoded by DRB1 gene. IAR is another example of new supertypic specificities, reflecting structural homologies between alleles at HLA class II loci.
HLA expression and function in single and double HLA‐B27‐transgenic mice
Authors: Kievits F. , Wliffels J. , Lokhorst W. , Boerenkamp W. J. , Ivanyi P.
Published: October 2008

The expression and function of HLA antigens in mice single transgenic for HLA‐B27.2 (sTGM‐B27.2) or double transgenic (dTGM) for HLA‐B27.2 and human β2microglobulin (hβ2m) were compared. B27.2 could be well detected on the cell membrane of lymphocytes of sTGM. However, the expression in sTGM was much lower than in dTGM mice. Nevertheless, also in sTGM mice, the B27‐transgene product possessed all functional properties of a class I HLA molecule. This was shown by the recognition and induction of antibodies and cytotoxic T cells, by the induction of “allo”‐immunity, including skin graft rejection, and by the ability to present viral antigens. In dTGM, the expression of B27 on peripheral blood lymphocytes, spleen and lymphnode cells was comparable to H‐2. However, on thymocytes, a relatively lower expression of HLA than H‐2 was observed. This low expression of B27 on thymocytes is in concert with the observation that B27 is expressed only in the medulla of the thymus and not detectable in the cortex.
No HLA‐DR specificity is associated with endometriosis
Authors: Maxwell C. , Kilpatrick D. C. , Hajning R. , Smith S. K.
Published: October 2008

Thirty‐one patients with endometriosis were typed for HLA‐A, B and DR antigens. No association was found between the disease and any DR specificity, which may be taken as evidence against an autoimmune aetiology.
Serological mapping of HLA‐epitopes with monoclonal antibodies and its interpretation by sequenced HLA‐molecules
Authors: Harpprecht J. , Olde K. , Westphal E. , Müller‐Ruchholtz W.
Published: October 2008

For the study of the epitope distribution on HLA class I molecules, blocking studies were carried out with a competitive radioimmuno assay using 3H labelled monoclonal antibodies (MAbs) against various HLA epitopes. The results were discussed with the help of known HLA amino acid sequences, and the positions of the following epitopes were suggested: A2/Aw69; A2/28; A2/11/25/26/28/29/30/31/Aw33/34; A25/32; Bw4; B7/Bw22,42; Bw6.
Lack of informative HLA restriction fragment length polymorphisms in autoimmune chronic active hepatitis
Authors: Eckardt G. S. , O'Brien R. M. , Mackay I. R. , Martinis L. De , Tait B. D.
Published: October 2008

Autoimmune chronic active hepatitis (CAH) is strongly associated with HLA‐B8, DR3. Accordingly, DNA was isolated from 10 HLA‐B8, DR3 control subjects and 11 patients with autoimmune CAH and analyzed for informative restriction fragment length polymorphisms using HLA‐DQβ and DRβ probes, and six enzymes, Hinc II, Bgl II, Bam HI, Rsa I, Taq I and Msp I. None of the polymorphic fragments demonstrable was discriminatory for autoimmune CAH. A genetic polymorphism in the HLA‐B8, DR3 region predisposing to autoimmune CAH may not have been detecting owing to an insufficient number of probes or enzymes used, or alternatively HLA‐DR3 is predisposing by an effect on immune regulation or suppression.
A simple and rapid method for HLA‐DQA1 genotyping by digestion of PCR‐amplified DNA with allele specific restriction endonucleases
Authors: Maeda M. , Murayama N. , Ishii H. , Uryu N. , Ota M. , Tsuji K. , Inoko H.
Published: October 2008

The second exon of the HLA‐DQA1 genes was selectively amplified from genomic DNAs of 72 HLA‐homozygous B cell lines by the polymerase chain reaction (PCR). Amplified DNAs were digested with HaeIII, Ddel, ScrFI, FokI and RsaI, which recognize allelic sequence variations in the polymorphic segments of the DQA1 second exon, and then subjected to electrophoresis in polyacrylamide gels. Eight different polymorphic patterns of restriction fragments were obtained, and seven were identical to patterns predicted from the known DNA sequences, correlating with each HLA‐DQw type defined by serological typing. The remaining one pattern cannot be explained from the sequence data, suggesting the presence of a novel DQA1 allele at the nucleotide level. This PCR‐RFLP method provides a simple and rapid technique for accurate definition of the HLA‐DQ types at the nucleotide level, eliminating the need for radioisotope as well as allele specific oligonucleotide probes and can be extended and applied to HLA‐DR, ‐Dw DP typing.
Molecular analysis of HLA‐D region genes in seropositive rheumatoid arthritis
Authors: McDaniel D. O. , Barger B. O. , Acton R. T. , Koopman W. J. , Alarcón G. S.
Published: October 2008

Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10−3, relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2× 10−5, RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10−2, RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, −7, −9 and −w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQwl. Using probes specific for the 5′ or 3′ regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5′ end and the 4.8 and 7.0 kb RFLPs to the 3′ end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5′ location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes.
Restriction fragment length polymorphism analysis of HLA haplotypes in families with Type I diabetes mellitus
Authors: Badenhoop K. , Schwarz G. , Bingley P. , Lewis V. , Drummond V. , Gale E. A. M. , Bottazzo. G. F.
Published: October 2008

Abstract: HLA Class II polymorphisms were analysed in 27 families with at least one Type I diabetic proband using Southern blotting technique according to 10th Histocompatibility Workshop Standards. The probes used were DRB, DQA1, DQB1 and DOB. We have studied 108 haplotypes and performed segregation analysis with HLA serology and restriction fragment length polymorphism (RFLP) data and compared “affected” with “non‐affected” haplotypes (not inherited by IDDM patients). RFLPs correlated well with DR and DQ serology and detected additional polymorphisms. In particular, DQB polymorphism analysis showed segregation of the DQw3 splits with 88.5% of the DR4 affected haplotypes bearing the DQw3.2 split (now DQw8) and 11.5% the DQw3.1 split (now DQw7) while in the non‐affected DR4 haplotypes 33.3% were DQw3.2 and 66.6% were DQw3.1. Haplotype analysis showed that DR4‐DQw3.2 was in strong linkage with the U fragment (2.1 kb Taq I) of DQA2 (DXa) and with the L fragment (5.4 kb BamH I) of DOB. This study confirms previous observations of DQB polymorphisms in heterozygous IDDM patients, supports the protective effect of DQw3.1 (DQw7) against the development of the disease and demonstrates the importance of DQw3.2 (DQw8) for susceptibility to Type I diabetes.
CD45 ligation in T cells regulates signal transduction through both the interleuhn‐2 receptor and the CD3/Ti T‐cell receptor complex
Authors: Gilliland L K. , Schieven G. L , Grosmaire L. S. , Damle N. K. , Ledbetter J. A.
Published: October 2008

Abstract: The cytoplasmic domain of the CD45 leukocyte cell surface antigen has recently been shown to possess protein tyrosine phosphatase (PTPase) activity. The existence of a cell membrane‐bound PTPase may represent a mechanism by which an activation signal, initiated by ligand binding to a surface receptor, is down‐regulated following delivery of the signal. Both the interleukin‐2 (IL2) growth factor receptor and the CD3/Ti T‐cell antigen receptor contain a subunit which is phosphorylated on tyrosine by an activated protein tyrosine kinase (PTK) during T‐cell activation. We compared the effect of CD45 ligation on signal transduction mediated by the binding of IL2 or anti‐CD3 to these two receptors. Immunoblotting with anti‐phosphotyrosine antiserum was used to investigate the effect of CD45 ligation on anti‐CD3‐ or IL2‐induced protein tyrosine phosphorylation. When CD3 and CD4S were triggered together, changes in the pattern of tyrosine phosphorylation of specific substrates was observed in comparison to the stimulus triggered through CD3 alone. In contrast, CD45 ligation did not alter the pattern of tyrosine‐phosphorylated proteins in “resting” T‐cell blasts responding to IL2, except for a mobility shift of a 55 kDa protein and increased phosphorylation of a 112 kDa substrate. The proliferative response of T cells to both anti‐CD3 or IL2 was inhibited by ligating CD45. The CD45 molecule down‐regulated CD3‐induced T‐cell activation when the CD45 and CD3 molecules were ligated simultaneously with immobilized antibodies. In contrast, immobilized CD45 mAb alone inhibited IL2‐induced proliferation, and the inhibition was not potentiated by simultaneously using a CD25 mAb which was non‐competitive for IL2‐binding. Furthermore, soluble anti‐CD4S partially inhibited proliferation in response to IL2, indicating that proximal association of CD45 and IL2 receptor molecules was not required for inhibition. We conclude that the PTPase activity of CD45 can uncouple both the antigen‐mediated and 112–mediated pathways of signal transduction in T cells, but appears to do so through different mechanisms.
Pre‐eclampsia is associated with HLA‐DR4 sharing between mother and fetus
Authors: Kilpatrick D. C. , Gibson F. , Livingston J. , Liston W. A.
Published: October 2008

Abstract: Full HLA‐A,B and DR typing was carried out on 92 women with proteinuric pre‐eclampsia, 80 of their husbands and 46 of their babies. The results were compared with corresponding data from 65 normotensive pregnancies involving primiparous women. The frequency of HLA‐DR4 was increased in the pre‐eclamptic women (RR 3.1; p< 0.005) and in the babies of pre‐eclamptic pregnancies (RR 2.6; p < 0.03). The strongest association, however, was with sharing of HLA‐DR4 between mother and fetus (RR 4.2; p = 0.01). There was no increase in HLA antigen sharing in general between spouses or maternal‐fetal pairs in pre‐eclampsia. Nor did pre‐eclamptic women exhibit increased homozygosity in general at any HLA locus. We conclude that genetic susceptibility to pre‐eclampsia depends at least partly on fetomaternal compatibility for a gene or genes associated with HLA‐DR4.
Restriction fragment length polymorphism of complement C4 in Japanese patients with rheumatoid arthritis and normal Japanes
Authors: Mimori Akio , Takeuchi Fujio , Tokunaga Katsushi , Maeda Hiroo , Matsuki Kazumasa , Matsuta Kunio , Nakano Keiichiro , Kosuge Eri , Yukiyama Yasushi , Omoto Keiichi , Miyamoto Terumasa
Published: October 2008

Abstract: Restriction fragment length polymorphism (RFLP) of the two genes for complement C4A and C4B was studied in 56 Japanese patients with rheumatoid arthritis (RA) and 161 normal individuals. Hindlll digestion revealed six common patterns, from which the segregation of three common RFLP‐types were deduced; 32‐15 kb, 32‐25‐15 kb, and 32‐20‐13‐6.5 kb. The last type showed positive associations with C4B5 and HLA‐DR4. In the RA patients, an increase of this type was found as well as a decrease of the 32‐15 kb/32‐25‐15 kb heterozygotes.
Monoclonal antibodies detecting discrete epitopes of human perforin
Authors: Geisberg Mark , Trapani Joseph A. , Dupont Bo
Published: October 2008

Abstract: Perforin is a cytolytic protein of natural killer (NK) cells and cytotoxic T cells (CTL). Purified perforin has been shown to cause cell lysis and to form stable pores in the target cell membrane, but its relevance to cytolysis in vivo is not clear. The gene for human perforin has been cloned, but monoclonal antibodies (mabs) have not been available. In order to study further its role in cytotoxicity, we have generated mabs to different regions of human perforin. Four mabs were produced from mice immunized with hybrid proteins comprising E. coli TrpE protein at the N‐terminus and different regions of human perforin at the C‐terminus. These proteins were made using the pATH expression plasmids into which fragments of perforin cDNA were subcloned. Monoclonal antibody PA1 was made from a mouse immunized with a hybrid protein containing the C‐terminal 240 amino acids (AA) of perforin, PE1 ‐ the N‐terminal 118 AA, and PB1 and PB2 ‐ the central 199 AA. The three plasmid constructs contained non‐overlapping cDNA segments which covered the entire sequence of perforin. All mabs reacted with the immunizing hybrid protein, but not with the other hybrid proteins, indicating that at least three epitopes are recognized by this set of mabs. All mabs immunoprecipitated a molecule of about 68 kd from lysates of metabolically‐labelled cytolytic large granular lymphocytic leukemia cells, but not from control lysates of non‐cytolytic promyelocytic U937 cells. These mabs should be of use in determining structure‐function relationships for perforin.
Lack of association between HLA and Schoenlein‐Henoch Purpura
Authors: Østergaard J. R. , Storm K. , Lamm L. U.
Published: October 2008

Abstract: The occurrence of HLA‐A, ‐B, and ‐C antigens was investigated in an unselected group of 26 consecutively admitted patients with Schoenlein‐Henoch Purpura. No significant associations were demonstrated.
Analysis of HLA‐DP in HLA‐DR/GLO recombinant families and in the population of south‐western France
Authors: Thornsen M. , Essaket S. , Cambon‐Thomsen A. , Robbins F. M. , Brtzman R. J. , Arnaud J. , Ohayon E.
Published: October 2008

Abstract: The existing estimates of the recombination fraction between DR and DP are quite variable and often based on anecdotal observations. We have estimated the DR/DP crossover frequency on the basis of families typed for HLA markers and GLD. The frequency of DR/GLO crossing over was 8.7% (23/264 informative meioses), maternal recombinations being about twice as frequent as paternal ones. Of 17 DR/GLO recombinant families typed for DPwl‐6, DP was informative in 11 (13 recombinations) but only one of these gave rise to a DR/DP crossover. According to these data the DR/DP recombination fraction is below I%, in contrast to some earlier published materials. HLA‐DR/DP haplotypic associations on 127 informative Caucasoid haplotypes have been evaluated. In agreement with previous studies, DR3 was positively associated with DPwl and, in addition, DR7 was found to be positively associated with DP‐blank (not DPwl‐6). The rare DPw6 allele is possibly associated with the DR4, Dw14 allele. The DR‐DP haplotype profiles suggest other associations which might become significant if larger materials are tested. The frequency of DP alleles in a random material (N = 201) was found to be in accordance with most of the previously published frequences on European Cauca‐soids with DPw4 as the predominating frequency (gene frequency 40%) and a blank frequency of 21%.
The association between HLA and rheumatoid artlmtis in Zimbabwean Blacks
Authors: Martell R. W. , Stein M. , Davis P. , West G. , Ernmsnuel J. , Du Toit E. D.
Published: October 2008

Abstract: HLA‐A, B, C, DR and DQ typing was done on 26 black Zimbabweans with rheumatoid arthritis and the respective antigen frequencies were compared with those in a group of 119 normal individuals from the same ethnic background. Only the DR4 antigen was significantly increased in frequency in the patients, confirming the association with this disease seen in other Black African populations.
HLA or HLA‐linked genes reduce birthweight in families affected by idiopathc recurrent abortion
Authors: Christiansen O. B. , Mathiesen O. , Riisom K. , Lauritsen J. G. , Grunnet N. , Jersild C.
Published: October 2008

Abstract: HLA typing was performed in 49 families, each containing at least one woman with a history of unexplained recurrent spontaneous abortion (RSA), and reproductive histories were recorded for the siblings. Abortion rate in sisters sharing two HLA haplotypes with the proband was significantly (p<0.01) increased, whereas abortion rates of brothers’wives seemed independent of the brothers’degree of HLA sharing with the proband. Birthweights of offspring of both the sisters and the brothers decreased with increasing HLA haplotype identity between the sibling and the proband (p = 0.05). The mean birthweight of infants of siblings sharing both parental haplotypes with the proband was 3158 g which was significantly (p<0.02) less than the average birthweight in Denmark (3417 g). Significantly (p < 0.05) decreased mean birthweight in infants of brothers who were HLA‐identical with the proband suggested that the disposition to growth retardation could be inherited with HLA also through the male gametes. It has been shown that, in their few successful pregnancies, women with RSA bear infants with a birthweight which is approximately 300 g less than normal. The present study demonstrated that the two obstetrical conditions, RSA and retarded fetal growth, share common genetic markers: HLA. It is suggested that HLA or HLA‐linked genes causing growth retardation in fetuses are part of the putative complex of genes involved in the pathogenesis of recurrent abortion.
A preliminary analysis of the 11.th International HistocompatibilitY Workshop monoclonal antibodies *
Authors: Marsh Steven G. E. , Krausa Peter , Bodmer Julia G.
Published: October 2008

Abstract: In the 11th International Histocompatibility Workshop pre‐screening study, HLA Class I and Class I1 monoclonal antibodies (mAb) were tested on panels of peripheral T and B cells and homozygous typing cell (HTC) lymphoblastoid lines. The 102 Class I mAb, of which 64 were new, were screened on 63 HTC lines and 20 peripheral T cells. The 144 Class II mAb were tested on 63 HTC lines, 20 peripheral B and 10 peripheral T cells. For Class I, 45 of the 102 mAbs tested proved to have clear and identifiable reaction patterns on both PBL and HTC lines and included several interesting new HLA‐A and ‐C locus antibodies. Of the 144 Class II mAb, of which 99 were new, 18 DR, 22 DQ and 7 DP antibodies were judged excellent. The DR antibodies included some which were antigen‐specific but the majority were complex antibodies, while the DQ antibodies, as previously, identified the majority of DQ antigens both singly and in combinations. The encouraging number of DP antibodies was interesting in the limited range of sites they appear to detect.
Novel putative promoter/enhancer sequences are shared by the mouse and human perforin (Pfp) genes
Authors: Trapani Joseph A. , Dnpont Bo
Published: October 2008

Abstract: This report describes the organization of the mouse pore‐forming protein (perforin) gene (Pfp), which is highly analogous to that of the corresponding human gene. Pfp comprises three exons, the first of which consists entirely of 5′ non‐coding sequence, separated by an intron of 1.94 kb from the two polypeptide‐coding exons. The promoter region of the gene shows strong similarity to that in humans, with six stretches of high homology noted within 0.7 kb of the mRNA cap site. However, many of the sequences of the human gene with similarity to previously described promoter/enhancer elements are poorly conserved in the mouse, suggesting that these motifs may be of no functional significance, and that control mechanisms for expression of Pfp may be highly specific to killer cells.
RFLP analysis of HLA‐DR5 haplotypes
Authors: Reed Elaine , McManus Peter , Suciu‐Foca Nicole
Published: October 2008

Abstract: The analysis of HLA‐DR5 haplotypes unravelled a new DRB3 polymorphism and permitted the identification of various associations between alleles of the DRB1 and DRB3 loci. This new polymorphism consists of a 10.5 kb Taql restriction fragment which was encountered in an African‐American family (JS). In Caucasoids, the DRwll allele has been previously observed only in association with the DRw52b allele. RFLP and oligonucleotide typing of HLA‐DRw52 alleles associated with DRwll showed, however, that 4 Caucasoid individuals from our panel carried the DRw52a allele and 1 the DRw52c allele. Similarly, DRwl2, which is usually associated with DRw52b, was encounterd with DRw52a in 1 Chinese and with DRw52c in an African‐American and a Chinese panel member. The study of DRB3 alleles associated with DRwll and DRwl2 indicates that, similar to serology, RFLP studies become particularly informative when individuals of different races and ethnic origins are studied.