A strong association between HLA-DR9 and gelatin allergy in the Japanese population

Kumagai, Toshiko; Yamanaka, Tatsuru; Wataya, Yasuhiko; Saito, Akiko; Okui, Toyo; Yano, Shoki; Tsutsumi, Hiroyuki; Chiba, Shunzo; Wakisaka, Akemi

doi:10.1016/s0264-410x(00)00555-7

Cited by 21 publications

(13 citation statements)

References 10 publications

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“…However, the binding motifs for many important alleles remain unknown or only partially characterized. Among these, the peptide binding motif for DRA1/B1*0901 (DR0901) 3 is interesting because of its prevalence in Asian populations and its association with type 1 diabetes (8-12) and gelatin allergy (13). This motif has been investigated previously (14, 15).…”

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confidence: 99%

The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9

James

Moustakas

Bui

et al. 2009

The Journal of Immunology

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Peptide binding to class II MHC protein is commonly viewed as a combination of discrete anchor residue preferences for pockets 1, 4, 6/7, and 9. However, previous studies have suggested cooperative effects during the peptide binding process. Investigation of the DRB1*0901 binding motif demonstrated a clear interaction between peptide binding pockets 6 and 9. In agreement with prior studies, pockets 1 and 4 exhibited clear binding preferences. Previously uncharacterized pockets 6 and 7 accommodated a wide variety of residues. However, although it was previously reported that pocket 9 is completely permissive, several substitutions at this position were unable to bind. Structural modeling revealed a probable interaction between pockets 6 and 9 through β9Lys. Additional binding studies with doubly substituted peptides confirmed that the amino acid bound within pocket 6 profoundly influences the binding preferences for pocket 9 of DRB1*0901, causing complete permissiveness of pocket 9 when a small polar residue is anchored in pocket 6 but accepting relatively few residues when a basic residue is anchored in pocket 6. The β9Lys residue is unique to DR9 alleles. However, similar studies with doubly substituted peptides confirmed an analogous interaction effect for DRA1/B1*0301, a β9Glu allele. Accounting for this interaction resulted in improved epitope prediction. These findings provide a structural explanation for observations that an amino acid in one pocket can influence binding elsewhere in the MHC class II peptide binding groove.

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confidence: 99%

The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9

James

Moustakas

Bui

et al. 2009

The Journal of Immunology

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“…Currently, the association between HLA class II genes and hypersensitivity reactions was revealed in part. For example, high frequency of DR9 was reported in Japanese patients with gelatin allergy (Kumagai et al 2001). HLA-DRB gene association was also reported in penicillin allergy, especially with high frequency of DR9 in penicillin-allergic patients presenting with urticaria and DR14 in benzylpenicilloyl-hypersensitive patients (Yang et al 2006).…”

Section: Discussionmentioning

confidence: 98%

HLA-DR9 and DR14 Are Associated with the Allopurinol-Induced Hypersensitivity in Hematologic Malignancy

Jung

Kim

Yoon

et al. 2014

Tohoku J. Exp. Med.

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Allopurinol, a widely used urate-lowering agent, is a leading cause of severe cutaneous adverse reactions (SCARs), especially in patients with HLA-B*58:01. Despite its routine use for the prevention of tumor lysisrelated hyperuricemia prior to chemotherapy, the risk of allopurinol-induced hypersensitivity has not been investigated in patients with hematologic malignancies. This retrospective cohort study was conducted to investigate the incidence and risk factors of allopurinol-induced hypersensitivity in patients at least 18 years of age with hematologic malignancies. We reviewed 463 patients who had ever taken allopurinol for the prevention of hyperuricemia prior to chemotherapy and had undergone serologic HLA typing as a pre-transplant evaluation from January 2000 to May 2010. Thirteen (2.8%) patients experienced maculopapular eruptions (MPE) and none experienced SCARs. Among subtypes of underlying hematologic malignancies, percentage of chronic myeloid leukemia was significantly higher in the allopurinol hypersensitivity group compared with the tolerant group (23.1% (3/13) vs. 5.9% (26/440), P = 0.044). According to HLA subtypes, the incidence of allopurinol-induced MPE was 4.0% in HLA-B58 (+) patients (2/50) and 2.7% in HLA-B58 (−) patients (11/403) but this difference was statistically insignificant. In contrast to HLA-B58, the frequencies of DR9 and DR14 were significantly higher in the allopurinolinduced MPE group compared with the allopurinol tolerant group (38.5% (5/13) vs. 13.6% (53/443), P = 0.019, and 38.5% (5/13) vs. 15.6% (41/440), P = 0.038, respectively). In conclusion, HLA-DR9 and DR14, but not HLA-B58, are associated with hypersensitivity reaction by allopurinol when administered in patients with hematologic malignancy prior to chemotherapy.

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“…In 1 communication from Japan, it was shown that HLA-DR9, unique to Asians, was typed in 57% of the gelatin IgE-positive patients-a significantly higher proportion than in the control group. 27 In our study, we did not ask about the ethnic origin of study subjects during interviews. However, a review of first and last names of the cases did not suggest Asian origin.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Anti-Gelatin IgE Antibodies in People With Anaphylaxis After Measles-Mumps-Rubella Vaccine in the United States

et al. 2002

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ABSTRACT. Objective. Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions.Methods. We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solidphase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events.Results. Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the

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A strong association between HLA-DR9 and gelatin allergy in the Japanese population

Cited by 21 publications

References 10 publications

The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9

The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 9

HLA-DR9 and DR14 Are Associated with the Allopurinol-Induced Hypersensitivity in Hematologic Malignancy

Prevalence of Anti-Gelatin IgE Antibodies in People With Anaphylaxis After Measles-Mumps-Rubella Vaccine in the United States

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