BRIEF COMMUNICATION Competent cellular immunity in allergic rhinitis patients with elevated IgE Michael

Bethesda,

W.

Yocum,*

Douglas

M.

Strong,**

and

James

D.

Lakin,***

Md.

Parameters of cell-mediated immunity (CJiI) xerc studied in 17 allergic rhinitis patients selected for markedly elevated totnl serum IgE levels (> 300 IlJ/ml) anti 14 normal controls. iWean serttm IgE levels tccre 1,481 IO/ml and 101 IU/ml in thr allergic and control groups, respectively (p < 0.001). Thew were no significant diffel’ences between the allergic patients and the norma. controls in delayed cutaneous hypersensitivity, in mitogen and antigen lymphocyte transformation in heterologous or au.tologous plasma, or in percentage of sheep erythrocyte rosettrs. The allergic patient group had a significantly higher percentage of sheep erythrocyte-antibodycomplement rosettes (p < 0.05). Xarl;rdly elernterl totfll swum IgB lelsels in nllergic rhinitis pnticnts u’pre not rtssociated with any ddwtnble impnirment of CXI.

In man congenital1 or acquired2 defects of cell-mediated immunity (CMI) may be accompanied by an &ration of total serum immunoglobulin E (IgE) or the development of spetifio reaginic antibody” In atopic dermatitis patients with marked elevations of serum IgE , scvwal C&II tlcfects have been described.‘~ 5 A possible inverse relationship between the total serum IgE level and the wmpetcncc of CM1 has been postulated in man based on these clinical observations and on recent information concerning rcaginic antibotly production in rodents.“, 7 We have tested this hypothesis in allergic rhinitis patients with markedly elevated total serum IgE by comparing scvcrai parameters of’ their CR41 with those of normal control subjects. METHODS basis

The 17 allergic rhinitis patients of 3 to 4 plus positiw prick

(20 to 34 yr of age; mean, 22 yr) were selected on the tests to at least 30 of 70 acroallrrgens and :I markedly

From the Department of Medicine, National Naval Medical Center? and the Clinical and Experimental Immunology Department, Naval Medical Research Tnstrtutc. Supported by the Bureau of Medicine and Surgery, Work Unit No. CICC-5-06843. The opinions or assertions contained herein are the private views of the authors and are not to hc construed as official or as reflecting the views of the Department of the Navy or the Department of Defense. Received for publication June 30, 1975. Accepted for publication Sept. 17, 1975. Reprint requests to: Dr. Douglas M. Strong, Tissue Bank, Naval Medical Research Institute, Rethesda, Md. 20014. *Lieutenant Commander, Medical Corps, United States Naval Heserw ; present address : Allergy-Immunology Unit, Henry Ford Hospital, Detroit, Mich. 48202. *‘Lieutenant Commander, Medical Service Corps, United States Navy. ‘“*Lieutenant Commander, Medical Corps, United States Naval Reserve; present address: Oklahoma Allergy Clinic, P.O. Box 26827, Oklahoma City, Okla. 73126. Vol.

57,

A’o.

4, pp.

384.388

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. .. .. :. : . .. i . A : . :

PATIENTS FIG.

1. Mean

total

serum

IgE

(17) levels

CONTROLS of

patient

and

(14) control

groups.

elevated (> 300 IU/ml) total serum IgE level. None had ever manifested atopic dermatitis or bronchial asthma. The 14 normal control subjects (20 to 44 yr of age; mean, 29 yr) were paid volunteers with a negative history of allergic disease and negative prick tests to TO aeroallergens. Neither the patients nor the controls had ever received corticosteroids. Prick skin tests to aeroallergens” (tree, grass, and weed pollens, molds, house dust, animal epidermal and environmental inhalants of 1: 10 w/v) were read at 20 min and graded on a O-4 plus scale.8 Delayed intracutaneous tests to 0.1 ml of Dermatophytin “0” (Candida) antigen,+ tetanus-diphtheria fluid 1: loo,* Dermatophytin (Trichophytin) mix 1: 30,” mumps toxoids 1 :lOO: and streptokinxse/streptodornase 40 U/10 U/ml$ were read at 48 hr and designated positive if induration exceeded 5 mm in diameter. Total serum IgE was measured in duplicate by the double-antibody radioimmunoassay method of Gleich, Averbeck, and Swedlund!) and a level greater than 300 IU/ml was considered markedly elevated for purposes of patient selection.lo The method detected IgE > 10 IU/ml whole serum. Mononuclear leukocyte separation, erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosette assays, and antigen and mitogen stimulations were performed as previously described in detail.11 Lymphocyte transformation was measured by radiolabeled thymidine incorporation.

RESULTS

The total serum IgE levels of the allergic and control groups are shown in Fig. 1; means + standard deviations were 1,421 f 1,354 and 101 t 140 W/ml for *Hollister-Stier Laboratories, Spokane, Wash. t Eli Lilly and Company, Indianapoli!, Ind. $Merrell-National Laboratories, Cincinnati, Ohio. QLederle Laboratories, American Cyanamid Co., Pearl

River,

N. Y.

386

Yocum,

Strong,

TABLE

I. Lymphocyte

and

J. ALLERGY

Lakin

transformation

to mitogens

and

antigens

in

CLIN.

heterologous

IMMUNOL. APRIL 1976

plasma

3-day Bkgd:

Highest IgEt patients (9) Total patients (17) Controls (14)

PHA

I

448 rt 84$ 546 f 88 476 z!c64

Con-A

Bkgd.

II. Percentage

of rosette-forming

26,146 k 3,108 31,181 f 2,385 37,934 f 2,828

Streptokinase/ streptodornese

Tetanus

19,545 & 3,558 20,99D i 2,247 22,221 i 3,866

Highest IgE patients (9) 856 f 159 11,146 f 1,591 13,659 f 1,249 Total patients (17) 1,439 f 288 11,342 i 1,427 Controls (14) 1,409 f 246 “Rackground counts per minute (cpm) of unstimulated lymphocytw. tPaticnts with total wrum IgE > 1,000 IU/ml. :Mean cpm + standard error of the mean of triplic~ntc cultures. TABLE

PWM

109,260 l 9,919 67,728 f 6,975 126,843 f 8,242 76,404 f 4,646 139,409 f 12,349 83,085 f 6,537

cells

E (%I

Highest IgE* patients (9) 49.9 f 1.8 Total patients ( 17) 53.2 f 2.1 55.2 f 2.1 Controls (14) NB: not significant. “Pnticnts \vitll total serum IgB > 1,000 W/ml.

Student’s t test

EAC

NS NS

(%I

42.5 f 3.3 42.3 f 1.9 35.0 f 1.9

Student’s t test

p < 0.05 p < 0.05

each respective group (p < 0.001). Zinc pdicnts hat1 an IgE level > 1,000 IV/ml ant1 overdofurther srlcetccl out of the group of 17 allergic patients and designated as a. third (highest IgE) gwmp. This groul) as well as the entire allergic group were subscyurntl~ compared with the cwntrol group for any~tlifferriiws in CMI. There were 110signifivailt cliffcrcnccs iir the iiieaii ilumbcr of positive delayed skin t>cstsamong the highest lgli: group 12.7s)) the entire allergic group (‘7.94), and the control groul) (22X?), respectively, Strcptokinasc/streptodornase clicitctl the highest percentage of positive tests in all snl)jects (76.3%). The results of 3-day mitogen and Lclay antigen lymphocyte transformation in hetcrologous plasma. arc shon-11in Table 1. All data for 3- and &day mitogen anti May antigen Iynplioc~tc transformation in hetcrologous and autologons plasma analyzetl by mean wunts per minutr or stimulation ratios failed to show significant tlifferciiws among the three groups. 142and II:AC rosettes cxpressctl as a perccntapc i SEM of 200 mononnclcar cells countctl are show1 in Table II. Both the highest IgE ilIlt1 the entire allergic groups hacl a higher percentage of EAC’ rosettes than the rontrol groups (I’ < 0.05). DISCUSSION

Recent findings in rodents suggest that helper T l,xmphoc\-tes (T cells) with carrier spccifieity cooperate with B Ipmphocytw with hapten specificity to initiate primary antihaptcnic IgII: antibody synthesis.‘;, ; Another subpopulation of 7’ dls with the same carrier spccificit~- is thought to suppress ongoing IgE antiI)otl,v synthesis,

as 1‘ ~11 inimniiosnppressioll

prior

to hapttw-carrier

immuniza-

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tion has been found to enhance and prolong the subsequent IgE antibody response.’ In man some T cell-deficient states have been accompanied by elevation of the total serum IgE,‘. ” and atopic dermatitis patients with marked elevations of serum 1gE may hare T cell defects. These CM1 defects in eczema include suppression of delayed cutaneous hypersensitivity (DCIL) , diminished contactant sensitization and in vitro lymphocyte transformation,-l and decreased percentage of E rosette mononuclear cells.” However, recent reports have described normal DCH,‘:’ mitogcn stimulation, ant1 percentage of E rosctte$* in atopic dermatitis patients. In asthma patients there are reports of suppressed DCH and lymphocyte transformation to ph~tohemagglntinin” and decreased percentage of E r0settes.l” There have heen no reports concerning the adequacy of CSII in allergic rhinitis patients with markedly elevated serum IgE levels. In the present report there were no significant differences found between 17 allergic rhinitis patients with total serum IgE > 300 IL/ml (including I) patients with IgE > 1,000 N/ml) and 1-C normal control subjects when compared by DCH, lymphocyte transformation to mitogens and antigens, and percentage of E rosette mononuclear cells. Thus no inverse relationship between serum IgE level and competcnc? of CM1 by the parameters measured was found. Our results agree with a rcceiit report which found no correlation between DCII and the intensity of immediate skin tests in allergic patients” and confirmed a previous report of normal lymphocyte transformation to SK/SD in allergic rhinitis patients.lh In the present study an increased percentage of EAC rosettes was found in the allergic patients; a similar elevation of EAc rosettes accompanied by a decrease in E rosettes occurs in primary imn~uiiocleficiency.~~ Although the strum IgE levels in our patients were lower than those in eczcma patients with concurrent allergic rcspiratorp disease,“” a patient reported to have a serum IgE level > 210,000 Il’/ml had no demonstrable defect in CMI.“’ Elevations in serum IgE may reflect specific reaginic antibody or polyclonal antihotly without detectable specificity, and separate controls may govern each of these levels.“’ In studies of the regulation of IgE synthesis in rodents, specific antihapten IgE antibody, not total serum lgE, was the parameter of B lymphocaytc activity nicasured.‘~~ i In the present report we selected patients with elevated total serum IgE and multiple specific reaginic antibodies to numerous aeroallergens in an attempt to clcmonstrate any defect in T cell function or CM1 which might h associated with ele\ation of polyclonal or specific reaginic serum IgE. Our inability to demonstrate a CM1 defect in these patients may reflect the inability of current in vitro methods to select the proper subpopulation of T cells for evaluation of function. The absence of a subpopulation of T lymphocytes normally exerting a suppressive effert on IgE B cells may not have been detectable among other normally functioning T cell subpopulations uncommitted to the regulation of IgE synthesis but engaged primarily in helper cell”, i or CM1 effector cell’” activities. Konctheless, within the levels of sensitivity of our techniques and the data obtained in this study, we were unable to demonstrate dcfcctivc CM1 in allergic rhinitis patients with markedly elevated total serum IgE levels and multiple specific reaginic IgE antihodics.

388

Yocum,

Strong,

and

Lakin

J. ALLERGY

CLIN.

IMMUNOL. APRIL 1976

We thank Mrs. Robin IV. Vidriek and Mrs. M. A. Myers for superb technical and assistance and Miss Judy G. Ford and Mrs. Barbara Johnson for excellent secretarial ance and preparation of this manuscript.

nursing assist-

REFERENCES T. A., and Terry, W. I~.: IgE in immunodeficirncy, Am. J. 1 Polmar, H. H., Waldmann, Pathol. 69: 499, 1972. 2 Lakin, J. D., Strong, D. M., and Sell, K. IV’.: Elevated total serum IgE following antihuman thymocyte globulin and total body x-irradiation in man, to be published in J. AI,LERGY CLIN. IMMUNOL. 3 Lakin, J. D., Strong, D. M., and Sell, K. W.: Polymyxin B reactions, 1gE antibody and T-cell deficiency: Immunochemical studies in a patient after marrow transplantation, Ann. Tntern. Med. 83: 204, 1975. 4 Lobitz, W. C., Jr., Honeyman, J. F., and Winkler, N. W.: Suppressed cell-mediated immunity in two adults with atopic dermatitis, Br. J. Dermatol. 86: 317, 1972. 5 Palaeios, J., Fuller, E. IV., and Blaylock, W. K.: Immunological capabilities of patients with atopic dermatitis, J. Invest. Dermatol. 47: 484, 1966. basis of reaginic antibody formation in vitro, 6 Ishizaka, K., and Kishimoto, T.: Cellular Reagin-mediated hypersensitivity, New in Goodfriend, L., editor: Mechanisms in allergy: York, 1973, Marcel Dekker, Inc., p. 63. 7 Tada, T., Okumura, K., and Taniguchi, M.: Cellular and humoral controls of reaginic antiL ., editor : Mechanisms in allergy : Reagin-medibody synthesis in the rat, in Goodfriend, ated hypersensitivity, New York, 1973, Marcel Dekker, Inc., p. 43. 8 Vanselow, N. A.: Skin testing and other diagnostic procedures, in Sheldon, J. M., Lovell, R. CT., and Matthews, K. P., editors: A manual of clinical allergy, Philadelphia, 1967! IV. B. Saunders Co., chap. 4. 9 Gleirh, G. J., Averbeck, A. K., and Swrdlund, H. A.: Measurement of IgE in normal and allergic serum by radioimunoassay, J. Lab. Clin. Med. 77: 690, 1971. 10 Marsh, D. G., Bias, W. B., and Ishizaka, K.: Genetic control of basal serum immunoglobulin E level and its effect on specific reaginic sensitivity, Proc. Natl. Acad. Sei. 71: 3588, 1974. 11 Strong, D. M., IVoody, J. N., Facktor, M. A., Ahmed, A., and Sell, K. TV.: tmmunological responsiveness of frozen-thawed human lymphocytes, Clin. Exp. Immunol. 21: 442, 1975. 12 Luckasen, J. R., Sabad, A., Goltz, R. W., and Kersey, J. IT.: T and B lymphocytes in atopic eczema, Arch. Dermatol. 110: 375, 1974. 13 Franz, M. L., and Galant, S. P.: Correlation of serum IgE and cutaneous delayed hypersensitivity (CDH) in atopic children, J. ALLERGY CLIS. ~MM~NOI,. 55: 113, 19i5. (Abst.) 14 Dupree, E., Friendman, J. M., Land, R. N., and Goldman, A. S.: Cell-mediated immunity in atopic dermatitis, J. ALLERGY CLIN. I~~IV~UXOL. 55: 102, 1975. (Abst.) Ford, R., and Forbes, 1. J.: Humoral 15 Grove, D. I., Burston, T. O., Wellby, M. L., Munro and cellular immunity in asthma, J. ALLERGY CLIN. I?I~~XUNOL. 55: 152, 1975. 16 Gupta, S., and Grieco, M. H.: T and B lymphocyte rosettes in bronchial asthma, J. ~LLERW CLIN. hlErIUNO1~. 55: 99, 1975. (Abst.) 1’7 Branch, L. B., Nelson, H. S., and Liptak, R.: Serum IgA and delayed hypersensitivity skin tests in allergic pat,ients, J. ALLERGY CLIN. IMMIXOL. 55: 113, 1975. (Abst.) 18 Rocklin, R. E., Pence, II., Kaplan, H., and Evans, R.: Cell-mediated immune response of ragweed-sensitive patients to ragweed antigen E. In vitro lymphocyte transformation and elaboration of lymphocyte mediators, J. Clin. Invest. 53: 735, 1974. 19 Luckasen, J. R., Rabad, A., Gajl-Prczalska, K. J., and Kersey, J. H.: Lymphocytes bearing complement receptors, surface immunoglobulins and sheep erythrocyte receptors in primary immunodeficiency diseases, Clin. Ex. lmmunol. 16: 535, 1974. 20 Johnson, E. E., Irons, J. S., Patterson, R., and Roberts, M.: Serum IgE concentration in atopic dermatitis. Relationship to severity of disease and presenre of atopic respiratory disease, J. ALLERGY CLIN. JMMUNOL. 54: 94, 1974. 21 Patterson, R., Oh, S. H., Roberts, M., and Hsu, C. C.: Massive polyclonxl hyperimmunoglobulinemia E, eosinophilia and increased IgE-bearing lymphocytc~s, Am. J. Med. 56: 553, 1975. 22 Amos, B.: Progress in immunology, New York, 1971, Academic Press, Inc.

Competent cellular immunity in allergic rhinitis patients with elevated IgE.

Parameters of cell-mediated immunity (CMI) were studied in 17 allergic rhinitis patients selected for markedly elevated total serum IgE levels (greate...
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