Multiple specimens from 124 patients from our clinic were evaluated for T4/T8 cell ratio over three to 28 months. Twenty-nine of 30 patients with the acquired immunodeficiency syndrome (AIDS), 58 of 71 patients with AIDS-related complex (ARC), and four of 23 patients at risk showed initial T4/T8 cell ratios of less than 0.8. which either remained unchanged or decreased. Seventeen of 23 AIDS patients and two of 20 ARC patients with a consistently low ratio (0.3 or less) died during the follow-up period. This indicated that the severity of disease could be predicted by periodical T4/T8 cell ratio studies. These serial studies appeared to be valuable in monitoring the course of patients with AIDS, ARC, and the human immunodeficiency virus infection and also in evaluating the effects of available drug treatment

Deegan, Michael J.

Fisher, Evelyn J.

Hayashi, Hajime

Markowitz, Norman

Mezger, Eugene

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 35 Number 1 Article 6 3-1987 T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex Hajime Hayashi Eugene Mezger Michael J. Deegan Evelyn J. Fisher Norman Markowitz Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Hayashi, Hajime; Mezger, Eugene; Deegan, Michael J.; Fisher, Evelyn J.; and Markowitz, Norman (1987) "T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex," Henry Ford Hospital Medical Journal : Vol. 35 : No. 1 , 30-32. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol35/iss1/6 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex Hajime Hayashi, PhD,* Eugene Mezger, MD,+ Michael J. Deegan, MD,* Evelyn J. Fisher, MD,* and Norman Markowitz, MD* Multiple specimens from 124 patients from our clinic were evaluated for T4IT8 cell ratio over three to 28 months. Twenty-nine of 30patients with the acquired immunodeficiency syndrome (AIDS), 58 of 71 patients with AIDS-related complex (ARC), and four of 23 patients at risk showed initial T4IT8 cell ratios of less than 0.8. which either remained unchanged or decreased. Seventeen of 23 AIDS patients and two of 20 ARC patients with a consistently low ratio (0.3 orless) died during the follow-up period. This indicated that the severity of disease could be predicted by periodical T4IT8 cell ratio studies. These serial studies appeared to be valuable in monitoring the course of patients with AIDS, ARC, and the human immunodeficiency virus infection and also in evaluating the effects of available drug treatments. (Henry Ford Hosp Med J 1987:35:30-2) The most commonly used laboratory tests for evaluating pa-tients with the acquired immunodeficiency syndrome (AIDS) are the anti-human immunodeficiency vims (anti-HlV) antibody test (1) and the subpopulation study of T-lymphocytes (helper/suppressor or T4/T8 cell ratio) (2), [Naming of the human immunodeficiency virus (HIV) for lymphadenopathy-associated vims (LAV), human T-cell lymphotropic vims type III (HTLV-III), immunodeficiency-associated virus (IDAV), and AIDS-associated retrovirus (ARV) was proposed by the subcommittee and endorsed by the executive committee of the Intemational Committee on the Taxonomy of Vimses (3).] Since the etiological agent of AIDS was established (4-6), the anti-HIV test has been used at blood donor stations to screen for the HIV-infected donor (7,8). It is also used at clinics as a diagnostic tool for patients with AIDS or AIDS-related complex (ARC). This serologic test can detect the antibody which indicates past or present infection with HIV, This test, however, is of limited value in the follow-up or prognosis of disease, because when a patient tests positive, the antibody usually stays positive there-after. The relationship of antibody levels to the course of disease is not established. Serial study of T4/T8 cell ratio is useful for monitoring the immunological status of a given patient over time. We are re-porting an application of the T4/T8 cell ratio in the prognosis of patients with AIDS and ARC. Clinical Specimens For purposes of clinical classification, the following criteria were adopted. The definition of AIDS was based on criteria from the Centers for Disease Control (9). ARC was defined to include those patients who were anti-HIV antibody positive by both en-zyme immunoassay (1) and Westem blot technique (10) and who did not have AIDS but displayed the symptoms, signs, or labora-tory abnormalities consistent with HIV infections. At-risk patients were HIV antibody positive without clinical manifesta-tions of disease. The 124 patients studied were classified into three groups: 1) 30 AIDS patients, 2) 71 ARC patients, and 3) 23 at-risk pa-tients. Blood specimens from these patients were evaluated over three to 28 months (average 8.7 months). Methods Testing for anti-HIV antibody Antibody to HIV was measured with the Abbott HTLV-III en-zyme immunoassay (Abbott Laboratories, North Chicago, IL) (1). Reactive semm specimens were tested by the Westem blot technique for confirmation (10). Testing for T-lymphocyte subset T-lymphocyte subset study was performed by direct immu-nofluorescence on a flow cytometer (Coulter EPICS V) with use of commercially available monoclonal antibodies (OKTll for total T, OKT4 for T-helper, and 0KT8 for T-suppressor cells from Ortho Pharmaceuticals, Raritan, NJ) (11). The buffy coat from heparinized blood was first reacted with each monoclonal antibody conjugated with fluorescence isothiocyanate for 30 minutes in an ice bath. After eliminating erythrocytes by a lysing reagent, tagged cells were fixed with 0.5% para-formaldehyde before testing. The percent of positive cells for each subset was measured on "gated" lymphocytes by flow cytometer The absolute count ofeach T-cell population was also calculated. Submitted for publication: April 23, 1987. Accepted for publication: May 19, 1987. *Department of Pathology, Division of Immunopathology, Henry Ford Hospital. tDepartment of f^thology. Division of Microbiology. Henry Ford Hospital. tOepartmenl of Internal Medicine, Division of Infectious Diseases, Henry Ford Hospital. Address correspondence to Dr Hayashi, Department of ftithology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202. 30 Henry Ford Hosp Med J—Vol 35, No 1, 1987 T-Lymphocyte Studies in AIDS—Hayashi et al Results The normal ranges of T-lymphocyte subpopulations estab-lished from 84 "normal" individuals at our laboratory are summarized in Table I . A T4/T8 cell ratio lower than 0.8 was considered "low" and 0,3 or less "extremely low." Table 2 summarizes a comparison of T4/T8 cell ratio and anti-HIV antibody in 124 patients (30 AIDS patients, 71 ARC pa-tients, and 23 at-risk patients). The HI V-antibody test detected exposure to the vims. When patients tested positive, they usu-ally stayed positive thereafter, regardless of the clinical course. On the other hand, the T4/T8 cell ratio can stratify the patients by a low (0.4 to 0.7) or extremely low (0.3 or less) ratio. These values were subsequently shown to be related to the clinical course. Table 3 shows the follow-up study of these patients by T4/T8 cell ratio. A total of 377 specimens from 124 patients were sub-mitted (average 3.0 specimens per patient). The T4/T8 cell ratio in those patients with low and extremely low ratios did not change. However, some patients who had an initially normal ratio fell to low or extremely low ratios during the follow-up period. One AIDS patient, nine ARC patients, and six at-risk patients demonstrated a reversal of T4/T8 cell ratios on subse-quent specimens. None of the patients improved the ratio on the subsequent specimens. Seventeen of 23 AIDS patients and two of 20 ARC patients with a consistently low ratio (0.3 or less) died during the follow-up period. This indicated that the severity of disease could be predicted by an extremely low T4/T8 cell ratio. The follow-up data for two patients are shown in Table 4 as examples. Decrease of the absolute count of T-lymphocytes was also evident with extremely low cell ratios, although the two were not always associated. Discussion Enzyme immunoassay for anti-HIV antibody is a simple test to detect a patient's exposure to the virus and is sensitive for screening at-risk patients. The T-lymphocyte subset study reveals the degree of suppression in T-lymphocytes. The simultaneous anti-HIV antibody and T4/T8 cell ratio as-says are most helpful for the stratification of patients with AIDS or ARC. These patients were found to have low or extremely low T4/T8 cell ratios. The patients with extremely low ratios had a poor prognosis. Patients with HIV antibody and normal T4/T8 cell ratios were usually in the asymptomatic at-risk group. Serial testing of the T4/T8 cell ratio is useful in monitoring the changing immunological status of the following groups: 1) parients with ARC (not full-blown AIDS); 2) individuals at risk (anti-HIV antibody positive by routine screening, but without symptoms); and 3) patients with HIV under antiviral therapy. References 1. Ftetricciani JC. Licensed tests for antibody to human T-lymphotropic vims type I I I : Sensitivity and specificity. Ann Intern Med 1985;103:726-9. 2. Bowen DL, Lane HC, Fauci AS. Immunopathogenesis of the acquired im-munodeficiency syndrome. Ann Intem Med 1985;103:704-9. Table 1 Normal Ranges for T-Lymphocyte Subpopulations (n = 84) Mean '/< Standard Deviation Normal % Ranges Mean ± Standard Deviation (absolute count) T i l (total) 72.3 7.2 57.3-86.7 (530-27 lO/mm') T4 (helper) 49.5 8.1 33.4-65.6 (400-1730/mmi) T8 (sup-pressor) 26.8 6.9 13.1-40.6 (150-990/mm3) T4/T8 cell ratio 2.0 0.6 0.8-3.2 Table 2 Comparison of Helper (T4) and Suppressor (T8) T-Lymphocyte Ratio and Anti-HIV Antibody in Three Patient Groups T4/T8 Cell Ratio Number of Patients (Anti-HIV Antibody Positive) AIDS ARC At Risk Normal: s= 0.8 1 (1) 13 (7) 19(6) Low: 0.4-0.7 6 (4) 38(35) 4(2) Extremely low: 0.3 23 (23) 20(18) 0 Total: 124 patients 30 (28) 71 (60) 23 (8) Table 3 Follow-up Study of Helper (T4) and Suppressor (T8) T-Lymphocyte Ratio in Three Patient Groups T4/T8 Cell Ratio Number of Patients (Deceased) Initial Subsequent Change AIDS ARC At Risk 3= 0.8 No change 0 4 13 i 1 9 6 0.4-0.8 No change 3 31 4 t o r i 3 7 0 =s 0.3 23 (17) 20(2) 0 Total: 124 30 (17) 71 (2) 23 i = decreased. t or I = fluctuated within abnormal range. Table 4 Follow-up Study TH T-Lymphocyte Subset T4 T8 T4/T8 Example 1: Patient with AIDS* 1st specimen 81% 40% 47% 0.85 (I318)t (640) (753) 6 months 74% 9% 58% 0.15 (783) (95) (614) 10 months 64% 8% 50% 0.16 (922) (50) (720) Example 2: Patient with ARC* 1 st specimen 57% 3% 59% 0.05 (629) (33) (658) 8 months 84% 1% 66% 0.02 (428) (5) (337) 8 months (deceased) *Both patients were anti-HIV positive. tAbsolute count. Henry Ford Hosp Med J—Vol 35, No 1, 1987 T-Lymphocyte Studies in AIDS—Hayashi et al 31 3. Brown F. Human immunodeficiency vims. Science I986;232:I486. 4. Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71. 5. Popovic M, Samgadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retrovimses (HTLV-III) from patients with AIDS and pre-AIDS. Science 1984;224;497-500. 6. Levy JA, Hoffman AD, Kramer SM, Landis JA. Shimabukuro JM, Oshiro LS, Isolation of lymphocytopathic retrovimses from San Francisco patients with AIDS. Science 1984;225:840-2, 7. Centers for Disease Control. Results of human T-lymphotropic vims type III test kits reported from blood collection centers—United States, April 22-May 19. 1985. MMWR 1985;34:375-6. 8. Laurence J, Bmn-Veninet F, Schutzer SE, et al. Lymphadenopathy-associ-ated viral antibody in AIDS: Immune correlations and definition of a carrier state. N Engl J Med I984;311; 1269-73. 9. Centers for DLsease Control. Revision of the case definition of acquired immunodeficiency syndrome for national reporting—United States. MM'WR 1985;34:373-5. 10. Esteban JI, Shi IV/-K, Tai G-C, Bodner AJ, Kay JWD, Alter HJ. Impor-tance of Westem blot analysis in predicting infectivity of anti-HTLV-III/LAV positive blood. Lancet 1985;2:1083-6. 11. Muirhead KA, Wallace PK, Schmitt TC, Frescatore RL, Franco JA, Horan PK. Methodological considerations for implementation of lymphocyte subset analysis in a clinical reference laboratory. Ann NY Acad Sci 1986;468:113-27. 32 Henry Ford Hosp Med J—Vol 35, No I , 1987 T-Lymphocyte Studies in AIDS—Hayashi et al 

T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex

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T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex

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