Evidence of a strong, positive association between atopy and the HLA class II alleles DR4 and DR7

Abstract

We observed that HLA-DR 4 and DR7 alleles are significantly implicated in their susceptibility to the disease and suggest that this susceptibility is more related to atopy than to specific responses to allergens. According to previous studies, we could also submit that in atopic patients with asthma, DR4 alleles at the least, could be more closely associated with atopy than with asthma per se. Conversely, we suggest that some allelic DQA1 and DQB1 sequences might confer protection against the disease.

HLA Class II Polymorphism in Cystic Fibrosis

“…We investigated genes of the MHC that encode molecules involved in immune response by presenting antigens for T cell recognition (21). We have previously reported an increase in the HLA class II alleles DR4 and DR7 in atopic and asthmatic patients (11). HLA-DR has also been found to be of prognostic significance in sarcoidosis, a systemic disease with prominent pulmonary involvement (22).…”

“…Therefore, genes that mediate susceptibility to atopy may influence disease severity. An association between human leukocyte antigen (HLA) class II antigens and the IgE response has been reported (8) and we have previously found strong associations between some major histocompatibility complex (MHC) class II alleles (DR4-DR7) and allergic diseases (9)(10)(11). It has also been shown that HLA-DR was the only class II antigen expressed in nasal polyps of CF patients (12).…”

“…Individuals were included only if they had no history of cancer, diabetes, cardiovascular disease, CF or any other major disease. This selection explains why only one control subject was carrier of DR4 and none of DR7 (11).…”

“…A panel of genomic DNA samples was previously obtained from nonatopic control subjects (9,11). The panel of CF genomic DNA samples was extracted from peripheral blood lymphocytes using the phenol-chloroform method (15).…”

Using single nucleotide polymorphisms as a means to understanding the pathophysiology of asthma

“…The human MHC on chromosome 6p, particularly HLA [113,114,115,116] and tumour necrosis factor (TNF) locus polymorphism [117,118], has also been extensively investigated, as has polymorphism in the 12q15-24 region [119,120]. SNPs in other candidate genes that have been investigated include, but are not limited to, the following: the α region of the T-cell receptor (TCR) α/δ locus [121], the α 1 -antitrypsin gene (α 1 -AT) [122,123,124], histo-blood-group genetic systems [125], the cystic fibrosis gene (ΔF508) [126,127], Gm allotypes of IgG genes [128], the Ig heavy chain γ 4 locus (IGHG4) [129], the Clara cell secretory protein (CC16) locus [130,131], the chemokine receptor loci on chromosome 3 [132,133], and the gene encoding angiotensin-converting enzyme (ACE) [134].…”