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Cellular or delayed-type hypersensitivity (DTH) can be assessed by intracutaneous testing with bacterial, viral and fungal antigens to which most healthy persons are sensitized. a positive skin test denotes prior antigenic exposure, T-cell competency and an intact inflammatory response (1,2) The reaction usually peaks 48 hours after antigen is introduced into the skin and is manifest as induration at the test site.
Recall antigens may be useful in evaluating delayed-type hypersensitivity by eliciting positive induration reactions 48 to 72 hours after intracutaneous administration. Except for mumps skin test antigen, most commonly used recall antigens were developed for other purposes, and the size of the reaction elicited may not be directly related to cellular immunity because of variability in antigen source and dose and skin test administration and measurement techniques. Useful antigens are those which elicit a reaction size ≥ 5 mm in more than 50% of normal individuals. The combination of results from skin testing with more than one antigen should result in detection of dth in at least 95% of normal subjects (2)
The inflammatory response associated with the DTH reaction is characterized by an infiltration of lymphocytes and macrophages at the site of antigen deposition. Specific cell types that appear to play a major role in the dth response include CD4+ and CD8+ T lymphocytes which leave the recirculating lymphocyte pool in response to exogenous antigen (3). Both CD4+ and CD8+ lymphocytes have been recovered from dth reactions elicited by Candida antigen (4).
In the literature, the incidence of dth reactions to unstandardized Candida antigens has been reported to vary from 52 - 89%, depending upon the strength of the antigen and the mm induration required for a positive test (5,6,7,8,9).
Published studies have reported that antigens of Candida albicans are useful in the assessment of diminished cellular immunity in persons infected with human immunodeficiency virus (10,11). Responses to dth antigens have been reported to have prognostic value in patients with cancer (5).
Table 1. Cellular hypersensitivity response to CANDIN® (candida albicans)
in healthy adults (15).
|N||Age range (years)||Number reactions ≥ 5 mm at 48 hours||Response overall|
|Study 1 (a)|
|Male||16||25 - 83||14|
|Female||2||61 - 69||2||78%|
|Male||20||23 - 63||13|
|Female||15||28 - 62||8||60%|
|(a) Control group in Table 2.|
Response to CANDIN® (candida albicans) in Healthy Adults (Table 1): In one group of 18 subjects, 14 (78%) of the individuals reacted to Candin® (candida albicans) with an induration response of ≥ 5 mm at 48 hours. In a second study of 35 subjects, 21 (60%) had induration reactions ≥ 5 mm at 48 hours. In this study, 65% of males tested positive compared to 5 3% of females; the mean induration in responding males was 12.8 mm and in responding females was 13.0 mm. When subjects in these studies were tested with two reagents, CANDIN® (candida albicans) and Mumps Skin Test Antigen, 92% were positive to at least one antigen, a higher response rate than to either antigen used alone (15).
Table 2. Cellular hypersensitivity response to CANDIN® (candida albicans)
in adults with AIDS, adults with HIV infection (no-AIDS-indicator conditions)
and adult control subjects (15)
|Group||Classification*||N||Zidovudine Use||CD4 T-cell Count||Mean Induration (mm)||N ≥ 5 (mm)||%|
|AIDS||A3,B3,C||32||14||4 - 483||145||3.35 (a)||9||28 (b)|
|HIV POS.||A1, A2, B1,B2||28||13||201-1065||455||5.67||15||54|
| * (reference 12)
(a) p = 0.01 compared to Control.
(b) p < 0.01 compared to Control.
Response to CANDIN® (candida albicans) in Adults with HIV Infection: In one study (Table 2), the skin test responses of adults with HIV infection were compared to those of healthy control subjects (age range AIDS 22 - 65, HIV positive 20 - 45, Controls 25 - 69). When HIV-infected subjects were classified by the CDC's 1993 revised classification system for HIV infection (12), a significant difference was found between AIDS patients and normal controls in both mean induration (p = 0.01) and proportion with ≥ 5 mm response (p < 0.01). The responses in HIV-infected patients (without AIDS-indicating conditions or AIDS-indicating CD4 T-cell counts) were less than in normal subjects, but the differences were not statistically significant.
In a second study involving 20 male patients (age range 26 - 57) diagnosed with AIDS based on clinical criteria only, one subject responded to CANDIN® (candida albicans) . In the same study 65% of the male control subjects had DTH reactions ≥ 5 mm to CANDIN® (candida albicans) (Table 1, Study 2). The mean induration response at 48 hours for control subjects was 8.33 mm compared to 1.78 mm for the AIDS subject. AIDS vs. control p-values were < 0 01 mean induration and < 0.01 induration ≥ 5 mm.
Because HIV infection can modify the DTH response to tuberculin, it is advisable to skin test HIV-infected patients at high risk of tuberculosis with antigens in addition to tuberculin (16). In a published study of DTH anergy, 479 subjects (334 males and 145 females) infected with HIV and being screened for tuberculosis were skin tested with several additional antigens including Candin® (candida albicans) supplied under IND to the investigators. Only 12% reacted to tuberculin ( ≥ 5 mm), 57% reacted to Candin® (candida albicans) ( ≥ 3 mm) and 60% reacted to either tuberculin or CANDIN® (candida albicans) or both. In this study, a 3 mm induration response to CANDIN® (candida albicans) was considered positive. The authors concluded that in HIV-infected subjects, testing with other DTH antigens increases the accuracy of interpretation of negative tuberculin reactions.
Table 3. Cellular hypersensitivity response to CANDIN® (candida albicans)
in adults with cancer (15).
|N||Age Range||Number reactions ≥ 5 mm at 48 hours||Response|
|Study 1||18||52 - 75||5||28%|
|Study 2||20||47 - 81||0||0%|
In one study of 18 patients with lung cancer, CANDIN® (candida albicans) elicited a positive induration response in five patients (28%). In a second series of 20 patients with metastatic cancer, no reactions ≥ 5 mm were observed (Table 3).
1. Middleton, E. Jr., Ree d, C.E., Ellis, F.E., Adkinson, N.F., Jr., Yunginger, J.W., Busse, W.W., Allergy Principles and Practice, 4th Ed., Vol II, pp 963-982, Mosby, St. Louis, 1993.
2. Bernstein, I.L., ed., Proceedings of the task force of guidelines for standardizing old and new technologies used for the diagnosis and treatment of allergy, J. Allergy Clin. Immunol., 82: 487-526, 1988.
3. Paul, W.E., Fundamental Immunology, 3rd Ed., pp 75-76, Raven Press, New York, 1993.
4. MacPhee, M.J., Gordon, J., Christou, N.V., Sanchez-Cantu, L., Rode, H.H., Cells recovered from human DTH reactions: phenotypic and functional analysis. Cellular Immunology, 151: 80-96, 1993.
5. Ahmed, A.R., Blose, D.A., Delayed-type hypersensitivity skin testing. A review. Arch. Dermatol, 119: 934-45, 1983.
6. Stimpson, P.G., Paty, J.G., Jr., Hudson, T., Lieberm an, P., Delayed hypersensitivity skin testing for assessing anergy in the mid-south. South. Med. J., 69: 424-426, 1976.
7. Kniker, W.T., Anderson, C.T., McBryde, J.L., Roumiantzeff, M., Lesourd, B., Multitest CMI for standardized measurement of delayed cutaneous hypersensitivity and cell-mediated immunity. Normal values and proposed scoring system for healthy adults in th e U.S.A . Ann. A llergy, 52: 75-82, 1984.
8. Gordon, E.H., Krouse, H.A., Kinney, J.L., Steihm, E.R., Klaustermeyer, W.B., Delayed cutaneous hypersensitivity in normals: choice of antigens and comparison to in vitro assays of cell-mediated immunity. J. Allergy Clin. Immunol., 72: 487-494, 1983.
9. Shannon, D.C., Johnson, G ., Rosen, F.S., Aus ten, K.F., Cellular reactivity to Candida albicans antigen, New Eng. J. Med., 275: 690-693, 1966.
10. Blatt, S.P., Hen drix, C.W ., Butzin, C .A., Freem an, T.M., Ward, W.W., Hensley, R.E., Melcher, G.P., Donovan, D.I., Boswell, N.R., Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients. Ann. Int. Med., 119: 177-183, 1993.
11. Colebunders, R.L., Lebughe, I., N zila, N., K alunga, D., Francis, H., Ryder, R., Piot, P., Cutaneous delayed-type hypersensitivity in patients with human immunodeficiency virus infection in Zaire. J. Acq. Immune Def. Synd., 2: 576-578, 1989.
15. Data on file, Allermed Laboratories, Inc.
16. CDC, Purified protein derivative (PPD) C tuberculin anergy and HIV infection: guidelines for anergy testing and management of anergic persons at risk of tubercu losis. Morbidity and Mortality Weekly Report. 40: No. RR-5, April 26, 1991.
Last reviewed on RxList: 5/28/2009
This monograph has been modified to include the generic and brand name in many instances.
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