MHC polymorphisms associated with HIV infection in Uganda

Abstracts

120

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HLA-DRB1, -DQB1, -DPB1 ALLELES OF HEMOPHILIA BROTHERS TREATED WITH COAGULATION FACTORS CONTAINED HIV-1 IN JAPAN Takato O. Yoshida, koichi Matsubara, Akira Kobayashi, Junichi Mimaya Hamamatsu University Schoolof Medicine, Hamamatsu: Chugai Parm.Co., Ltd., Tokyo; Children's Hospital ofShizuokaPref.. Shizuoka, Japan HLA class II allelesofJapanese hemophilia brotherstreatedwith coagulation factorscontainedHIV·1 has been pursured whysome one is infected and survived over12 years as comparedwkh earlydeath brothers, and also why some one is not infected with k usinga new DNA typing methods, TMA-HPA (transcription mediated amplification - hybridization protection assay) and PCR-HPA. Wewill reportthe studieson HLA-DRB1, -ooB1, -DPB1 allelesof the manyhemophilia brothers relatedto theirimmune responses. Atmoment weshow HLA class II haplotypes of 6 brothers as tollows: (Fl

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P655 HLAANTIGENS IN HEMOPHILIACS WITII LONGTERMNON PROGRESSIVE arvINFECTION ~io*,

A. Gringeri", M. Zarantooello*, E. Santagostino°, P.M. Mammcci°, R.

~~~~:~'=~~~~~~~p:;imd University of Milan, Italy Severalinvestigators havelooked for associations between HLA type!! anddisease state inIllY-infi:clcd individuals anda varietyof HLAantisenshave been associated with disease~ioo. During the last few years it bas become clear

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fullowed-up sina: seroconversion (1981-1986, median 1983),we ~ 11 asymptomatic subjectswi CD4 cell COlIIl!S greatertllan500/mm fur at Jeast 10 ~ ana 1IO anti theraDv_ We coriiDared the frequencies ofHLA antigens in these 8 patients se in'2'4 bemopbiliacs who serOCOllverted in the same yefiod but already' died S 3-13years after seroconversion (median 9 years),3.of tile8 Long TermNonProgressoisandnoneof the 24 dead ~ theBI7 antl~' a lowfrequency antigenin tileItalianpopulation (6.23 %) (Fisher'sexacttest: .0094;odds rano by Haldane'modification of WoOlf's Du:tbod =33.727). ian-MeIer estimation and Cox regression analvsis were used to ~ tileWle BI7 antigenin: sumval~p SIOl1 to ~ CD4 cell countIlIUII <200,lII11O\I8 our wbolecohort of . iac patients. Noneof tile a CD4cell deoletion BI7positi¥e ~ died, progressed to AIDS or <2OOlllUll' overtile 10or Q1O!eye;l!S offollow~.lndividualswith In7 had a slowerrate ofCD4 cellf!epletioo f}1J4 <200p=Q.027)_ Thesedata C a r r i•e d .

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p657 HLA AND HTLV • WORKSHOP REPORT Sonoda S., Yashiki So, Kuwayama M., Fujiyoshi T., Jacobson S., Manns A., Alcalay D., Pombo M., Hammond MG., Nikbin B., Blank A" and Cartier L. Department of Virology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan and HLA & HTLV study group Nine laboratories from Japan, USA, France, Brazil, South Africa, Iran, Colombia and Chile participated to analyze HLA class I and class II alleles associated with HTLV-I and HTLV-II carriers, ATL and HAMffSP patients from different ethnic groups. HTLV-I carriers of Japanese, Iranian, Caribbean, South American Blacks, South American native Indian and South African Blacks had HLA-A alleles (AI, A2, A3, All, A23, A24, A26, A30, A31, A33, A34) and B alleles (B7, B44. B5DREG, 840) which were segregated ATL and HAMffSP patients. HLA-class II alleles were also found to be segregated. Thus, ATL patients increased HLA-DRBl*0901 and DQBI*m032 significantly, while HAMrrSp patients increased HLA-DRBI*OlOl and DQBl*0501. These DRBI, DQ81 alleles were mutually exclusive between ATL and HAMrrSp patients. These results suggested the ethnic background of HTLV-r carriers and disease susceptible alleles relevant ATL and HAMffSP patients. In addition, South American native carrying HTLV-II had a unique category HLA class 11 alleles which was etbnically segregated from those of HTLV-I carrier populations.

P654 MHC POLYMORPHISMS ASSOCIATED WITH HIVINFECTION IN UGANDA S. Ali, F. Lyagoba", B. Biryawaho", A. Nunn", H-V. Wagner', S. Malambav, 1. Whitworth', D. W. Mulder',A. V.S. Hill. WeUcome Trust Centre for Human Genetics, Oxford University, UK and MRC Programme onAIDS inUganda. Uganda Virus Research Institute',Entebbe,Uganda. Several studies have suggested associations between various manifestation of HIV infection and particular HLA class I and class 1I genes. However, thesesma!! scale studies, which have beendonein several ethnic gronps and in different geogrophieal areas, have shown little consistency. The current large-scale study differs from previousinvestigations by beingset in a rural Africancommunitywhere transmission

of HIV iswholly by heterosexual contact. Participants in this case-control study were selected from a cohort of 10,000 people incluster of 15villages in theMasaka District of Uganda thathavebeen under surveillance since 1989. Each of 272seropositives has been matched with2 or more seronegative controlsfor ethnicgroup,area of residence, age and sex. The population

prevalence of IllV infection is 8.2% in adults. Typing of DNA was performedhy the PeR and SSO technique. At the HLA-DR locus, HLA-DRBl'1302 was found less frequently in those withIllV infection thanin controls. The antigen frequency in the cases (0=259) was12.0% versus 172%incontrols (n=698; odds ratio=O.65, P<0.05). The samples have also been typed for TNF-a promoter polyrnorphisms at positions -238and-308. These variant alleles are present at frequencies of 0.078 and 0.072 respectively. Theposition -308TNF polymorphism didnot showanyassociation with susceptibility to IllV infection. However, homnzygotes for the -238 TNF promoter variant were significantly less frequent (0/242) in the IllV positive individuals than in 650 controls (2.2%, P=0.014). These data suggest that altered expression ofthe TNF-a gene may affect susceptibility toIllV infection.

p656 HLA CLASS I ALLELES IN HIV-J NON-INFECTED PERSONS WITH LONGTERM SEXUAL CONTACT TO HIV-I INFECTED SPOUSES, Yupa Urwiiitaroonl.2, Arnomrat Romphruk', Sahawat Barusrux'r', Chintana Puapairoj'and Chanvit Leelayuwar'". , Department nfClinical Immunology, AMS, KKU 2 BloodTransfusion Centre,MED, KKU, KHON KAEN40002, THAILAND. The evidence for the MIlC association with rapid progression to death after IllY infection is well established. However, the role of the MIlC in the viral infection is not known. This study aimed to study the distribution of lILA class I alleles in non-infected individuals with sexually active IllY-I positive partners. Four males and seven females who have been long term sexually contacted to IllY-I positive spouses without using condom (contact group) were typed for lILA class I by ARMS using the 12WS primers. The contact group has been negative for antiIllV and proviral IllY-I DNA after exposure to infected partners for at least one year. The allele frequencies of lILA-A, -B and -C were compared to those of 100 ethnicallymatched Northeastern Thais (control group). lILA-A2 (0203,0207) and -Cw7 (0701/213) were found in 10/11 and 7/11 in the contact group. Although the finding indicates the increase of these alleles, there is no statistical difference of these alleles between the contact and control groups. Interestingly, lILA-A33 with combination of HLA-B44 was found to be increase in the contact non-infected group (p = 0.007). The results suggest the involvement of the MHC in the resistance to viral infection. We are investigating whether different viral strains are involvedby direct sequencing of the viral Pol and Gag genes.

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POSSIBLB HLA ASSOCIATION WITH SUSCEPTIBILITY TO HTLV-l TROPICAL SPASTIC PARAPARBSIS IN ISRAEL IN IRA!lIAll JOS AS COJIPARBD TO RTLV-l ASSOCIATED MYELOPATHY III JAPAll Shohat Batya, Achiron Anat, Narinski Ronit, Kochba Ilan, sidi Yekezkel, Sonoda Shunro, Osame Mitsuhiro, Klein Tirza. Inst. of Hematol, Tissue Typing Lab, Beilinson Med Cntr, Petah Tiqva, Israel and Third Dept. of Int Med, Faculty of Med, Kagoshima, Japan. To determine whether genetic factors are responsible for the high rate of human T lymphotropic virus type 1-associated myelopathy (HAM/TSP) in the Iranians in Israel, we studied the HLA phenotype of 12 patients with HAM/TSP, 1 with ATL, 8 HTLV-1 asymptomatic carriers and 28 seronegative Iranian Jews, HLA, A,B,C antigen typing was done according to the standard assay, HLA DR low resolution oligotyping was determined by PCR-SSP. The B52 antigen associated with HAM/TSP was found in the HAM patients at a frequency of 75%. In 4 of 7 patients with the HLA B52 antigen, this antigen was associated with DRB1*1502 and DQB1* 0601 antigens. These results were highly significant, This pattern found in the Israelis is similar to the one found in Japanese HAM. These findings demonstrate that identical genetic factors may be responsible for disease deVelopment in UTLV~1-infected persons worldwide.