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求玑冯
9 years ago
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1 DOH90- DC-1014 (

2 (1) 6-7 (2) 8-9 (3) 10 (4) (5) 13 (6) (7)

3 HIV 21 CD8 + CD38 HLA-DR CD4 + T (HPV) 50.0% (16/32) 50.0% (16/32) 8-9% 12.5% (4/32) 56.3% (18/32) 55.6% (10/18) HIV 21 CIN-1 (CIS) HIV HIV Immunophenotyping by flow cytometry Hormonal assay cellular immunity and functional assay HIV (HPV) 2

4 Abstract To test the relationship between the cellular immunity and different menstrual cycles and the prevalence of HPV infection in HIV-seropositive women, totally 32 subjects were enrolled. Immunophenotyping of peripheral blood during the follicular and luteal phases was composed of total cell count, lymphocyte count, CD4 +, CD8 +, and their activating markers including CD25, CD69, HLA-DR, CD28, CD38, etc. Pap smear was performed every 6 months. HPV typing of cervical smear was performed by PCR on various menstrual phases using various primers for HPV. Virus loading was checked on each blood sampling. Pap smear revealed active inflammatory reaction (class II) in 18 women (56.3%). Fungal infection was most frequent (55.6%, 10/18). The HPV positive rate was 50.0% (16/32) with malignant type and 12.5% (4/32) with benign type. During the follow up, two women with CIS and two with CIN-1 of uterine cervix were noted. The activating antigens (HLA-DR, CD38) were elevated on CD8 + T cells of these women. All these alterations seemed not related to menstrual cycle. Therefore, we concluded 1) the CD8 + T cells were increased and activated in women with HIV infection and these alterations were not affected by various menstrual cycles, 2) cervical inflammation especially fungal infection was common in these women, and 3) the prevalence of malignant type HPV infection was also high in these women that intensive Pap smear examination is recommended. Key words HIV, HPV, menstruation,cellular immunity 3

5 _ ( ) DOH90-DC (50.0%) HPV 4 (12.5%) 18 (56.3%) CD4 10 (10/18, 55.6%) Immunophenotyping NK cell B T CD4 + /CD8 + CD8 + HLA-DR CD38 CD HPV HIV HPV 3. HIV HIV cellular immunity HPV 4

6 5

7 1999 3,400 HIV (, human immunodeficiency virus) 280 AIDS 1,900 AIDS , % % (1) (2-4) (5,6) (7) HIV HPV (8) (9) HIV, (10) (11,12) HIV HPV 6

8 HIV 7

9 I II 1 a Estrodiol Progesterone b Immunophenotyping cell count lymphocyte count CD4 + CD8 + activation marker CD25, CD69, HLA-DR, CD28, CD38 etc flow cytometry c.c immunophenotyping : (monoclonal antibodies) FACScan flow cytometry-three color CD4 CD8T : Simultest (FITC CD45/PE CD14) Leucogate Simultest (FITC IgGI/PEIgG2,γ1/γ2) negative control Simultest (FITC CD3/PE CD19) Simultest (FITC CD3/PE CD16+56) Fastimmune (FITC CD4/PE CD69/PerCP CD3) Fastimmune (FITC CD8/PE CD69/PerCP CD3) FITC CD4/PE CD25/PerCP CD3) 8

10 FITC CD8/PE CD25/PerCP CD3) FITC CD4/PE CD28/PerCP CD3) FITC CD8/PE CD28/PerCP CD3) FITC CD4/PE HLA- DR//PerCP CD3) FITC CD8/PE HLA- DR/PerCP CD3) 3cc estrodiol progesterone c Pap smear: pap smear CD4 +, d Cervical smear: PBS PCR primer HPV type 6,11,16,18 (17), CD4+,HPV e Virus loading virus loading 2 a) Immunophenotyping virus load b) Immunophenotyping virus load 9

11 48 32 HIV CD (50.0%) HPV 4 (12.5%) 18 (56.3%) CD4 10 (10/18, 55.6%) Immunophenotyping NK cell B T CD4 + /CD8 + CD8 + HLA-DR CD38 CD4 + 10

12 32 HIV 21 (10) HIV 32 HIV HIV HPV (17-18) HIV (9,19-21) CIN CD4 500/mm 3 60% CIN (22) HPV (type 16 18) 50.0% 12.5%, Sun (9) 83% (17-18) 8-9% (CD /mm 3 ) HIV 4 Class III (12.5%) 4 11

13 ? HPV 21 HIV (21,23) HIV cellular immunity 10,000 (24) HIV HIV CD4/CD8 CD8 HLA-DR CD38 HIV (14-16) CD4 CD

14 HIV HIV HPV HIV 13

15 European collaborative study. Children born to women with HIV-1 infection: natural history and risk of transmission. Lancet 1991; 337: Lindgren S., Anzen B., Bohlin A-B., et al. HIV and Child-bearing: Clinical outcome and aspects of mother-to-infant transmission. AIDS 1991; 5: Gibb S., Wara D. Paediatric HIV infection. AIDS 1994; 8 (suppl 1): S Quilligan EJ. Obstetrics and Gynecology. JAMA. 1995; 273: Pinchun P. Management of HIV infected pregnant women in Chonbuin Hospital. J Med Assoc Thailand 1994; 77: Rabin DL, Boekeloo BO, Marx ES, et al. Improving office based physician's prevention practices for sexually transmitted diseases. Ann Int Med 1994; 121: Zanetta G., Maneo A., Colombo A. et al HIV infection and invasive cervical carcinoma in an Italian population: the need for closer screening program in seropositive patients. AIDS 1995; 9: Sun XW. Kuhn L. Ellerbrock TV. Et al. Human papillomavirus infection in women infected with the human immunodeficiency virus (see comments) (Journal Article) New Engl J Med 1997; 337: Ellerbrock TV, Wright TC, Bush TJ, Et al. Characteristics of menstruation in women infected with human immunodeficiency virus. Obstet Gynecol 1996; 87: Mestecky J, Kutteh WH, Jackson S. Mucosal immunity in the female 14

16 genital tract: relevance to vaccination efforts against the human immunodeficiency virus. AIDS Research. Hum Retrov 1994; 10 (suppl 2): S Ho HN, Chao KH, Chen CK, et al. The activation status of T and NK cells in endometrium throughout menstrual cycles, normal and abnormal pregnancy. Hum Immunol 1996; 49: Clerici M, Giogi JV, Chou CC, et al. Cell mediated immune response to human immunodeficiency virus type 1 (HIV-1) in seronegative homosexual men with recent sexual exposure to HIV-1. J Infect Dis 1992; 165: Ho HN, Hultin LE, Mitsuyasu RT, et al. Circulating HIV-specific CD8 + cytotoxic T cells express CD38 and HLA-DR antigen. J Immunol 1993; 150: Giorgi JV, Ho HN, Hiriji K, et al. CD8 + lymphocyte activation at HIV-1 seroconversion: development of HLA-DR + CD38 + CD8 + cells is associated with stable CD4 + cell levels. J Inf Dis 1994; 170: Febas J, Kaplan AH, Hausner MA, et al. Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-hiv CD8 + lymphocyte activity. J Inf Dis 1995; 172: Chen TM, Pecoraro G, Vittorio D. Genetic analysis of in vitro progression of human papilloma virus-transfected human cervical cells, Cancer Res 1993; 53: Chen TM. Chen CA. Wu CC, et al.the genotypes and prognostic significance of human papilloma virus in cervical cancer. Int J Cancer 1994:57: Conti M, Aganossi A, Parazzin F, et al. HPV- HIV infection and risk of cervical intraepithelial neoplasia in former intravenous drug abusers 15

17 Gynecol Oncol 1993;49: Meulen J, Eberhandt HC, Laundor J, et al. Human Papillomavirus (HPV) infection; HIV infection and cervical cancer in Tanzania, East Africa. Int J Cancer.1992; 51: Anonnymous. Risk for cervical disease in HIV infected women-new York. MMWR 1990;39: Cohn JA, Gagnon S, Spence MR, et al. The role of human papillomavirus deoxyribonucleic acid assay and repeated cervical cytologic examination in the detection of cervical intraepithelial neoplasia among human immunodeficiency virus-infected women. Am J Obstet Gynecol 2001; 184: Spinilclo A, Capuzzo E, Tenti P, et al. Adequacy of screening cervical cytology among human immunodeficiency virus-seropositive Women. Gynecol Oncol 1998; 69: Wright TC, Subbarao S, Ellerbrock TV, et al. Human immunodeficiency virus 1 expression in the female genital tract in association with cervical inflammation and ulceration. Am J Obstet Gynecol 2001; 184:

18 32 HIV HPV typing Benign Malignant Pap smear Menstrual cycle normal normal Irregular, endometrial hyperplasia Irregular, ATH normal Regular, fungal infection (+) normal normal Regular, fungal infection (+) Regular, fungal infection (+) normal inflammation Regular Regular, herpes infection (+) inflammation Regular, fungal infection (+) inflammation Regular normal Regular, thalassemia inflammation Amenorrhea, fungal infection normal regular inflammation normal Irregular, huge myoma Irregular, huge myoma inflammation regular normal regular normal regular inflammation Regular, infection - Bartholin cyst inflammation regular inflammation regular normal regular 17

19 normal fungus infection (+) Inflammation fungus infection (+) CIN-III CIS regular normal fungus infection (+) inflammation fungus infection (+) inflammation fungus infection (+) normal regular CIN-1 fungus infection (+) normal regular normal regular normal regular CIN-1 regular Inflammation condyloma Normal regular Normal regular 18

20 21 HIV 30 T Absolute number of cells /mm 3 CD4 + CD8 + Normal (N=30) 1084± ±203 HIV-positive (N=21) 406± ±407 Mean±SD 21 HIV 30 HIV-positive Normal control % follicular luteal follicular luteal B cells 14.1± ± ± ±6.4 T cells 64.3± ± ± ±7.5 CD8 cells 44.8± ± ± ±4.7 NK cells 17.5± ± ± ±7.3 Mean±SD (%) 19

21 HIV 21 T B HIV-positive Normal control % follicular luteal follicular luteal CD8 (CD3 + CD8 + ) HLA-DR + /CD ±6.4 a 37.3±5.5 b 7.8±9.8 a 8.1±9.0 b CD38 + /CD ±8.2 c 44.8±7.7 d 8.9±5.7 c 9.1±7.9 d CD69 + /CD ± ± ± ±6.6 CD25 + /CD ± ± ± ±2.8 CD4 (CD3 + CD4 + ) HLA-DR + /CD ± ± ± ±5.0 CD38 + /CD ± ± ± ±6.4 CD69 + /CD ± ± ± ±8.2 CD25 + /CD ± ± ± ±4.8 Mean±SD, abcd P< 0.05 compared between HIV-positive and normal women by Mann-Whitney U test. 20

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20110420 愛滋病與結核病防治台北榮民總醫院感染科國立陽明大學醫學系王永衛醫師它是什麼? 愛滋病毒 (HIV) 後天免疫缺乏病毒愛滋病 (AIDS) 後天免疫缺乏症候群愛滋病 1980 年迄今 Million 50 45 40 35 30 25 20 15 1 First cases of