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November 27, 1987, Vol 258, No. 20 >
ARTICLE | November 27, 1987

Immunotherapy With Allergens FREE

Peter S. Creticos, MD; Philip S. Norman, MD
JAMA. 1987;258(20):2874-2880. doi:10.1001/jama.1987.03400200080008
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Article
References

IMMUNOTHERAPY is the art of administering increasing doses of a specific extract comprising allergens to which the sensitive (atopic) individual would respond with allergic symptoms on natural environmental exposure in an attempt to alter that patient's immunologic response and thereby ameliorate the allergic patient's typical symptoms.

Immunotherapy has its roots in the early immunization work carried out by Pasteur, Jenner, and others that led to the development of highly effective vaccines that have virtually eradicated a wide variety of diseases such as smallpox and polio. As practiced for the treatment of allergic diseases, it is based on the work of two English physicians, Noon and Freeman,1,2 who in 1911 attempted to immunize grass "hayfever" sufferers with serial injections of grass-pollen extract. Although in their opinion the mechanism of action was that of an "antitoxin" produced against a "pollen toxin," their studies established that significant clinical improvement correlated with changes

REFERENCES

1 +
Noon L:  Prophylactic inoculation against hayfever . Lancet 1911;;1:1572.
2 +
Freeman J, Noon L:  Further observations on the treatment of hayfever by hypodermic inoculations of pollen vaccine . Lancet 1911;;2:814-817.
3 +
Prausnitz C, Küstner H:  Studies on supersensitivity . Zentralbl Bakteriol 1921;;86:160-169.
4 +
Ishizaka K, Ishizaka T:  Human reaginic antibodies and immunoglobulin E . J Allergy 1968;;42: 330-363.
5 +
Cooke RA, Barnard JH, Hebald S, et al:  Serologic evidence of immunity with coexisting sensitization in a type of human allergy (hay fever) . J Exp Med 1935;;62:733-750.
6 +
Loveless MH:  Immunological studies of pollinosis: IV. The relationship between thermostable antibody in the circulation and clinical immunity . J Immunol 1943;;47:165-180.
7 +
Lichtenstein LM, Holtzman NA, Burnett LS:  A quantitative in vitro study of the chromatographic distribution and immunoglobulin characteristics of human blocking antibody . J Immunol 1968;;101: 317-324.
8 +
Norman PS:  The clinical significance of IgE . Hosp Pract 1975;;10:41-49.
9 +
Ishizaka T, Hirata F, Ishizaka K, et al:  Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells . Proc Natl Acad Sci USA 1980;;77: 1903-1906.
10 +
Lewis RA, Austen KF:  Mediation of local homeostasis and inflammation by leukotrienes and other mast cell dependent compounds . Nature 1981;;293:103-108.
11 +
Wasserman SI:  Mediators of immediate hypersensitivity . J Allergy Clin Immunol 1983;;72:101-115.
12 +
Lichtenstein LM, Schleimer RP, MacGlashan DW Jr, et al:  In vitro and in vivo studies of mediator release from human mast cells , in Kay AB, Lichtenstein LM, Austen KF (eds): Asthma III: Physiology, Immunopharmacology and Treatment . London, Academic Press Inc, 1984;, pp 1-18.
13 +
Naclerio RM, Meier HL, Kagey-Sobotka A, et al:  Mediator release after nasal challenge with allergen . Am Rev Respir Dis 1983;;128:597-602.
14 +
Creticos PS, Adkinson NF Jr, Kagey-Sobotka A, et al:  Nasal challenge with ragweed pollen in hay fever patients . J Clin Invest 1985;;76:2247-2253.
15 +
Creticos PS, Peters SP, Adkinson NF Jr, et al:  Demonstration of peptide-leukotriene release following nasal antigen challenge in vivo . N Engl J Med 1984;;310:1626-1630.
16 +
Proud D, Togias A, Naclerio RM, et al:  Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen . J Clin Invest 1983;;72:1678-1685.
17 +
Nagy L, Lee TH, Kay AB:  Neutrophil chemotactic activity in antigen-induced late asthmatic reactions . N Engl J Med 1982;;306:497-501.
18 +
Naclerio RM, Proud D, Togias AG, et al:  Inflammatory mediators in late antigen-induced rhinitis . N Engl J Med 1985;;313:65-70.
19 +
Oertel HL, Kaliner M:  The biologic activity of mast cell granules for causing late phase reactions . J Immunol 1981;;127:1398-1402.
20 +
Gleich GJ:  The late phase of the immunoglobulin E-mediated reaction: A link between anaphylaxis and common allergic disease . J Allergy Clin Immunol 1982;;70:160-169.
21 +
Dolovich J, Hargreave FE, Chalmers R, et al:  Late cutaneous allergic responses in isolated IgE-dependent reactions . J Allergy Clin Immunol 1973;;52:38-46.
22 +
Lichtenstein LM, Ishizaka K, Norman PS, et al:  IgE antibody measurements in ragweed hay fever: Relationship to clinical severity and the results of immunotherapy . J Clin Invest 1973;;52: 472-482.
23 +
Platts-Mills TAE, von Maur RK, Ishizaka K, et al:  IgA and IgG anti-ragweed antibodies in nasal secretions . J Clin Invest 1976;;57:1041-1050.
24 +
Rocklin RE, Sheffer AL, Greeineder DK, et al:  Generation of antigen-specific suppressor cells during allergy desensitization . N Engl J Med 1980;; 302:1213-1219.
25 +
Lichtenstein LM, Norman PS, Winkenwerder WL:  A single year immunotherapy for ragweed hay fever: Immunologic and clinical studies . Ann Intern Med 1971;;75:663-671.
26 +
Creticos PS, Van Metre TE, Mardiney MR, et al:  Dose response of IgE and IgG antibodies during ragweed immunotherapy . J Allergy Clin Immunol 1984;;73:94-104.
27 +
Aalberse RC, van der Gaag R, van Leuwen J:  Serologic aspects of IgG4 antibodies . J Immunol 1983;;130:722-726.
28 +
Van der Zee JS, van Swieten P, Aalberse RC:  Serologic aspects of IgG4 antibodies: II. IgG4 antibodies form small non-precipitating immune complexes due to functional monovalency . J Immunol 1986;;137:3566-3571.
29 +
Behrens BL, Clark RAF, Marsh W, et al:  Modulation of the late asthmatic response by antigen specific IgG in an animal model . Am Rev Respir Dis 1984;;130:1134-1139.
30 +
Lichtenstein LM, Norman PS, Winkenwerder WL:  Clinical and in vitro studies on the role of immunotherapy in ragweed hay fever . Am J Med 1968;;44:514-524.
31 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Immunotherapy of hay fever with ragweed antigen E: Comparisons with whole pollen extract and placebos . J Allergy 1968;;42:93-108.
32 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Maintenance immunotherapy in ragweed hay fever . J Allergy 1971;;47:273-282.
33 +
Norman PS, Lichtenstein LM:  The clinical and immunologic specificity of immunotherapy . J Allergy Clin Immunol 1978;;61:370-377.
34 +
Van Metre TE, Adkinson NF Jr, Amodio FJ, et al:  A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever . J Allergy Clin Immunol 1980;;66:500-513.
35 +
Norman PS:  Specific therapy in allergy, pro (with reservations) . Med Clin North Am 1974;;58: 111-125.
36 +
Norman PS:  Immunotherapy , in Ishizaka K (ed): Progress in Allergy . Basel, Switzerland, S Karger AG, 1982;, vol 32, pp 318-346.
37 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Trials of alum-precipitated pollen extracts in the treatment of hay fever . J Allergy Clin Immunol 1972;;50:31-44.
38 +
Johnstone DE:  Study of the role of antigen dosage in the treatment of pollinosis and pollen asthma . AJDC 1957;;94:1-5.
39 +
Aas K:  Hyposensitization in house dust allergy asthma . Acta Paediatr Scand 1971;;60:264-268.
40 +
Warner JD, Price JF, Soothill JF, et al:  Controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with asthma . Lancet 1978;;2:912-915.
41 +
Metzger WJ, Donnelly BA, Richardson HB:  Modification of late asthmatic responses (LAR) during immunotherapy for Alternaria-induced asthma . J Allergy Clin Immunol 1983;;71:119.
42 +
Taylor WW, Ohman JL Jr, Lowell FC:  Immunotherapy in cat-induced asthma: Double-blind trial with evaluation of bronchial responses to cat allergen and histamine . J Allergy Clin Immunol 1978;;61:283-287.
43 +
Ohman JL, Findlay SR, Leitermann KM:  Immunotherapy in cat-induced asthma . J Allergy Clin Immunol 1984;;74:230-239.
44 +
Graft DF, Valentine MD:  Immunotherapy in allergy , in Kaplan AP (ed): Allergy . New York, Churchill Livingstone Inc 1985;, pp 679-692.
45 +
Turkeltaub PC, Rastogi SC, Baer H, et al:  A standardized quantitative skin-test assay of allergen potency and stability: Studies on the allergen dose-responsive curve and effect of wheal, erythema, and patients selection on assay results . J Allergy Clin Immunol 1982;;70:343-352.
46 +
Committee on Safety of Medicines:  CSM update: Desensitising vaccines . Br Med J 1986;;293: 948.
47 +
Lockey RF, Benedict LM, Turkeltaub PC, et al:  Fatalities from immunotherapy (IT) and skin testing (ST) . J Allergy Clin Immunol 1987;;79: 660-677.
48 +
Phanuphak P, Kohler PF:  Onset of polyarteritis nodosa during allergic hyposensitization treatment . Am J Med 1980;;68:479-485.
49 +
Yang WH, Dorval G, Osterland CK, et al:  Circulating immune complexes during immunotherapy . J Allergy Clin Immunol 1979;;63: 300-307.
50 +
Stein MR, Brown GL, Lima JE, et al:  A laboratory evaluation of immune complexes in patients on inhalant immunotherapy . J Allergy Clin Immunol 1978;;62:211-216.
51 +
Marsh DG, Lichtenstein LM, Campbell DH:  Studies on 'allergoids' prepared from naturally occurring allergens: I. Assay of allergenicity and antigenicity of formalinized rye group I component . Immunology 1970;;18:705-722.
52 +
Norman PS, Lichtenstein LM, Marsh DG:  Studies on allergoids from naturally occurring allergens: IV. Efficacy and safety of long-term allergoid treatment of ragweed hay fever . J Allergy Clin Immunol 1981;;68:460-470.
53 +
Metzger WJ, Patterson R, Zeiss CR, et al:  Comparison of polymerized and unpolymerized antigen E for immunotherapy of ragweed allergy . N Engl J Med 1976;;295:1160-1164.
54 +
Grammer LC, Zeiss CR, Suszko IM, et al:  A double-blind placebo controlled trial of polymerized whole ragweed immunotherapy of ragweed allergy . J Allergy Clin Immunol 1982;;69:494-499.
55 +
Rocklin RE:  Clinical and immunologic aspects of allergen-specific immunotherapy in patients with seasonal allergic rhinitis and/or allergic asthma . J Allergy Clin Immunol 1983;;72:323-334.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Noon L:  Prophylactic inoculation against hayfever . Lancet 1911;;1:1572.
2 +
Freeman J, Noon L:  Further observations on the treatment of hayfever by hypodermic inoculations of pollen vaccine . Lancet 1911;;2:814-817.
3 +
Prausnitz C, Küstner H:  Studies on supersensitivity . Zentralbl Bakteriol 1921;;86:160-169.
4 +
Ishizaka K, Ishizaka T:  Human reaginic antibodies and immunoglobulin E . J Allergy 1968;;42: 330-363.
5 +
Cooke RA, Barnard JH, Hebald S, et al:  Serologic evidence of immunity with coexisting sensitization in a type of human allergy (hay fever) . J Exp Med 1935;;62:733-750.
6 +
Loveless MH:  Immunological studies of pollinosis: IV. The relationship between thermostable antibody in the circulation and clinical immunity . J Immunol 1943;;47:165-180.
7 +
Lichtenstein LM, Holtzman NA, Burnett LS:  A quantitative in vitro study of the chromatographic distribution and immunoglobulin characteristics of human blocking antibody . J Immunol 1968;;101: 317-324.
8 +
Norman PS:  The clinical significance of IgE . Hosp Pract 1975;;10:41-49.
9 +
Ishizaka T, Hirata F, Ishizaka K, et al:  Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells . Proc Natl Acad Sci USA 1980;;77: 1903-1906.
10 +
Lewis RA, Austen KF:  Mediation of local homeostasis and inflammation by leukotrienes and other mast cell dependent compounds . Nature 1981;;293:103-108.
11 +
Wasserman SI:  Mediators of immediate hypersensitivity . J Allergy Clin Immunol 1983;;72:101-115.
12 +
Lichtenstein LM, Schleimer RP, MacGlashan DW Jr, et al:  In vitro and in vivo studies of mediator release from human mast cells , in Kay AB, Lichtenstein LM, Austen KF (eds): Asthma III: Physiology, Immunopharmacology and Treatment . London, Academic Press Inc, 1984;, pp 1-18.
13 +
Naclerio RM, Meier HL, Kagey-Sobotka A, et al:  Mediator release after nasal challenge with allergen . Am Rev Respir Dis 1983;;128:597-602.
14 +
Creticos PS, Adkinson NF Jr, Kagey-Sobotka A, et al:  Nasal challenge with ragweed pollen in hay fever patients . J Clin Invest 1985;;76:2247-2253.
15 +
Creticos PS, Peters SP, Adkinson NF Jr, et al:  Demonstration of peptide-leukotriene release following nasal antigen challenge in vivo . N Engl J Med 1984;;310:1626-1630.
16 +
Proud D, Togias A, Naclerio RM, et al:  Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen . J Clin Invest 1983;;72:1678-1685.
17 +
Nagy L, Lee TH, Kay AB:  Neutrophil chemotactic activity in antigen-induced late asthmatic reactions . N Engl J Med 1982;;306:497-501.
18 +
Naclerio RM, Proud D, Togias AG, et al:  Inflammatory mediators in late antigen-induced rhinitis . N Engl J Med 1985;;313:65-70.
19 +
Oertel HL, Kaliner M:  The biologic activity of mast cell granules for causing late phase reactions . J Immunol 1981;;127:1398-1402.
20 +
Gleich GJ:  The late phase of the immunoglobulin E-mediated reaction: A link between anaphylaxis and common allergic disease . J Allergy Clin Immunol 1982;;70:160-169.
21 +
Dolovich J, Hargreave FE, Chalmers R, et al:  Late cutaneous allergic responses in isolated IgE-dependent reactions . J Allergy Clin Immunol 1973;;52:38-46.
22 +
Lichtenstein LM, Ishizaka K, Norman PS, et al:  IgE antibody measurements in ragweed hay fever: Relationship to clinical severity and the results of immunotherapy . J Clin Invest 1973;;52: 472-482.
23 +
Platts-Mills TAE, von Maur RK, Ishizaka K, et al:  IgA and IgG anti-ragweed antibodies in nasal secretions . J Clin Invest 1976;;57:1041-1050.
24 +
Rocklin RE, Sheffer AL, Greeineder DK, et al:  Generation of antigen-specific suppressor cells during allergy desensitization . N Engl J Med 1980;; 302:1213-1219.
25 +
Lichtenstein LM, Norman PS, Winkenwerder WL:  A single year immunotherapy for ragweed hay fever: Immunologic and clinical studies . Ann Intern Med 1971;;75:663-671.
26 +
Creticos PS, Van Metre TE, Mardiney MR, et al:  Dose response of IgE and IgG antibodies during ragweed immunotherapy . J Allergy Clin Immunol 1984;;73:94-104.
27 +
Aalberse RC, van der Gaag R, van Leuwen J:  Serologic aspects of IgG4 antibodies . J Immunol 1983;;130:722-726.
28 +
Van der Zee JS, van Swieten P, Aalberse RC:  Serologic aspects of IgG4 antibodies: II. IgG4 antibodies form small non-precipitating immune complexes due to functional monovalency . J Immunol 1986;;137:3566-3571.
29 +
Behrens BL, Clark RAF, Marsh W, et al:  Modulation of the late asthmatic response by antigen specific IgG in an animal model . Am Rev Respir Dis 1984;;130:1134-1139.
30 +
Lichtenstein LM, Norman PS, Winkenwerder WL:  Clinical and in vitro studies on the role of immunotherapy in ragweed hay fever . Am J Med 1968;;44:514-524.
31 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Immunotherapy of hay fever with ragweed antigen E: Comparisons with whole pollen extract and placebos . J Allergy 1968;;42:93-108.
32 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Maintenance immunotherapy in ragweed hay fever . J Allergy 1971;;47:273-282.
33 +
Norman PS, Lichtenstein LM:  The clinical and immunologic specificity of immunotherapy . J Allergy Clin Immunol 1978;;61:370-377.
34 +
Van Metre TE, Adkinson NF Jr, Amodio FJ, et al:  A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever . J Allergy Clin Immunol 1980;;66:500-513.
35 +
Norman PS:  Specific therapy in allergy, pro (with reservations) . Med Clin North Am 1974;;58: 111-125.
36 +
Norman PS:  Immunotherapy , in Ishizaka K (ed): Progress in Allergy . Basel, Switzerland, S Karger AG, 1982;, vol 32, pp 318-346.
37 +
Norman PS, Winkenwerder WL, Lichtenstein LM:  Trials of alum-precipitated pollen extracts in the treatment of hay fever . J Allergy Clin Immunol 1972;;50:31-44.
38 +
Johnstone DE:  Study of the role of antigen dosage in the treatment of pollinosis and pollen asthma . AJDC 1957;;94:1-5.
39 +
Aas K:  Hyposensitization in house dust allergy asthma . Acta Paediatr Scand 1971;;60:264-268.
40 +
Warner JD, Price JF, Soothill JF, et al:  Controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with asthma . Lancet 1978;;2:912-915.
41 +
Metzger WJ, Donnelly BA, Richardson HB:  Modification of late asthmatic responses (LAR) during immunotherapy for Alternaria-induced asthma . J Allergy Clin Immunol 1983;;71:119.
42 +
Taylor WW, Ohman JL Jr, Lowell FC:  Immunotherapy in cat-induced asthma: Double-blind trial with evaluation of bronchial responses to cat allergen and histamine . J Allergy Clin Immunol 1978;;61:283-287.
43 +
Ohman JL, Findlay SR, Leitermann KM:  Immunotherapy in cat-induced asthma . J Allergy Clin Immunol 1984;;74:230-239.
44 +
Graft DF, Valentine MD:  Immunotherapy in allergy , in Kaplan AP (ed): Allergy . New York, Churchill Livingstone Inc 1985;, pp 679-692.
45 +
Turkeltaub PC, Rastogi SC, Baer H, et al:  A standardized quantitative skin-test assay of allergen potency and stability: Studies on the allergen dose-responsive curve and effect of wheal, erythema, and patients selection on assay results . J Allergy Clin Immunol 1982;;70:343-352.
46 +
Committee on Safety of Medicines:  CSM update: Desensitising vaccines . Br Med J 1986;;293: 948.
47 +
Lockey RF, Benedict LM, Turkeltaub PC, et al:  Fatalities from immunotherapy (IT) and skin testing (ST) . J Allergy Clin Immunol 1987;;79: 660-677.
48 +
Phanuphak P, Kohler PF:  Onset of polyarteritis nodosa during allergic hyposensitization treatment . Am J Med 1980;;68:479-485.
49 +
Yang WH, Dorval G, Osterland CK, et al:  Circulating immune complexes during immunotherapy . J Allergy Clin Immunol 1979;;63: 300-307.
50 +
Stein MR, Brown GL, Lima JE, et al:  A laboratory evaluation of immune complexes in patients on inhalant immunotherapy . J Allergy Clin Immunol 1978;;62:211-216.
51 +
Marsh DG, Lichtenstein LM, Campbell DH:  Studies on 'allergoids' prepared from naturally occurring allergens: I. Assay of allergenicity and antigenicity of formalinized rye group I component . Immunology 1970;;18:705-722.
52 +
Norman PS, Lichtenstein LM, Marsh DG:  Studies on allergoids from naturally occurring allergens: IV. Efficacy and safety of long-term allergoid treatment of ragweed hay fever . J Allergy Clin Immunol 1981;;68:460-470.
53 +
Metzger WJ, Patterson R, Zeiss CR, et al:  Comparison of polymerized and unpolymerized antigen E for immunotherapy of ragweed allergy . N Engl J Med 1976;;295:1160-1164.
54 +
Grammer LC, Zeiss CR, Suszko IM, et al:  A double-blind placebo controlled trial of polymerized whole ragweed immunotherapy of ragweed allergy . J Allergy Clin Immunol 1982;;69:494-499.
55 +
Rocklin RE:  Clinical and immunologic aspects of allergen-specific immunotherapy in patients with seasonal allergic rhinitis and/or allergic asthma . J Allergy Clin Immunol 1983;;72:323-334.

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