HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. II. Response after ragweed immunotherapy.

Abstract

In the preceding paper (1), we reported a significant striking association between Dw2 and IgE and IgG antibody (Ab) 1 responses to Ra5 in ragweed-allergic Caucasian subjects as a result of natural exposure to ragweed pollen. The question arose as to whether this relationship might change after parenteral immunization with much higher dosages of ragweed antigens. Such treatment, known as immunotherapy or hyposensitization, is commonly administered to ragweed-allergic patients to alleviate their allergic symptoms (2). Effective treatment is normally accompanied by high levels of serum IgG Ab toward ragweed antigens, especially the principal component, antigen E (AGE) (3).Whereas the adult dosage of inhaled Ra5 is probably no more than 60 ng over the 8-wk period of ragweed pollination (4), cumulative annual immunotherapeutic dosages of Ra5 are usually at least one or two orders of magnitude higher. We will show that such immunotherapy induces good immunoglobulin G (IgG) Ab responses to Ra5 in all ragweed-allergic individuals who possess Dw2, whether or not they produced IgE and/or IgG Ab to Ra5 before therapy, whereas the prevalence and level of IgG Ab response in persons lacking Dw2 are both much lower. Despite an extreme degree of heterogeneity in the type of therapy and antigen dosage, the association between IgG Ab response to Ra5 and Dw2 becomes increasingly stronger and more significant over a 3-yr period of therapy. Materials and MethodsPatients. The study group was comprised of 61 highly ragweed-allergic patients, who were a subset of the 86 patients included in the "clinic group," in the preceding paper (1). As previously stated, there was a bias toward selecting Ra5 responders, and, therefore, the proportion of Ra5+ subjects (23%) was higher than the value of ~9% one might expect in a random sample of ragweed-allergic subjects (cf. data for Westinghouse study group in ref. 1).

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

“…The difference in responsiveness was correlated with the H-2 genotype of the strain. Marsh et al 32 have suggested that the enhanced IgE response to highly purified pollen allergens such as antigen E and Ra5 is associated with a particular HLA haplotype. In the present study, however, none of the SAR traits, OG-specific IgE levels, or total serum IgE levels showed positive linkage to 6p21, which is where the HLA genes are located.…”

Alternative G1m, G2m and G3m Allotypes of IGHG Genes Correlate with Atopic and Nonatopic Pathways of Immune Regulation in Children with Bronchial Asthma

“…The involvement of several genes has been proposed. The genes include those specific to the allergen, particularly MHC class II molecules from chromosome 6 [1, 2, 3] involved in antigen presentation and the α chain of the T cell receptor, encoded on chromosome 14q11 [4]. In addition, a strong genetic linkage was reported for the IL-4 gene cluster on chromosome 5, involved in B cell activation [5, 6].…”

Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57

“…The mechanism of TDI-induced asthma is still unknown but recent evidence suggests an immunological mechanism [4]. In fact, TDI-induced asthma and extrinsic asthma have a similar pattern of inflammatory cell infiltration in bronchial biopsies [5,6]; inhalation challenge with TDI causes an increase in circulating CD8+ lymphocytes and eosinophils in sensitized subjects [7]; and an association with human leucocyte antigen (HLA) class II genes is documented both in TDIinduced asthma [8] and in allergen-induced asthma [9,10].…”